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In this article, we describe a very rare case of pituitary acidophilic stem cell adenoma, accompanied by a literature review. We present the case of 33-year-old woman with a history of amenorrhea, galactorrhea, elevated prolactin levels, and pituitary tumor. Despite suppression of prolactin levels with cabergoline, the pituitary tumor continued to increase in size and the patient developed clinical symptoms and biochemistry consistent with the diagnosis of acromegaly due to acidophilic stem cell adenoma, an extremely rare subtype of mixed growth hormone/prolactin adenoma, which behaves more aggressively and has a lower surgical cure rate compared to the pure GH-secreting adenoma. The patient had in vitro fertilization 2 years after the successful pituitary surgery and delivered healthy twins. To our knowledge, this is the only case report which describes acromegaly developing during cabergoline treatment. This case also highlights the importance of having a correct histopathological diagnosis to determine the behavior of the tumor and decide on further management.

Today much attention is paid to the study of the pituitary ultrastructure of laboratory animals and humans. But there is not enough available literature to study the most important organ of internal secretion of productive animal. The aim of our work is to study the structure of the ultrastructure of cells of the anterior pituitary gland of cattle in the definitive period of postnatal ontogenesis. Histological, morphometric, and electron microscopic techniques were used to study the cellular composition of the anterior pituitary gland of cattle. It was revealed that the anterior lobe of the pituitary gland occupies 64 % of the entire pituitary parenchyma, while the posterior and middle lobes occupy 27% and 9%, respectively. After using general histological methods there are detected the functionally inactive chromophobes (41%) and chromophilic cells, which include acidophils (38%) and basophils (21%) in the anterior lobe of the pituitary gland. The electron microscopic studies in the parenchyma of the anterior pituitary gland let find Somatotropes that differ in the presence of a large number of secretory granules in the cytoplasm. Lactotropes are less common than somatotropes and differ from them in larger secretory granules. Corticotropes, gonadotropes and thyrotropes with a minimum content of secretory granules are the least detected. All identified endocrine cells are at different stages of functional activity.

The Hawaiian mongoose (Herpestes auropunctatus) is a seasonally breeding mammal whose pituitary gland resembles that of other Viverridae. Certain features, such as a prominent pars tuberalis interna and a double-layered pars intermedia forming a cup for the neurohypophysis, are unique. With the light microscope, five different cell types can be recognized in the pars distalis after staining with periodic acid-Schiff (PAS)-orange G. Two types of acidophils are seen, a small yellow-staining cell and a large angular orange cell. Two basophilic cells are also seen, one with fine PAS-positive cytoplasmic granules and the other with coarse PAS-positive granules in the cytoplasm. The last cell type seen is the chromophobe. Differential cell counts indicated an altered distribution of chromophils in the ventral pars distalis of the female mongoose with changing season and reproductive status, but the most striking change was a decreased percentage of basophils in the pars distalis during the nonbreeding season.

OBJECTIVE To determine the effects of prenatal administration of ethanol on cell count in pars distalis of pituitary gland in the rat pups. STUDY DESIGN Experimental study. PLACE AND DURATION OF STUDY Department of Anatomy, College of Physicians and Surgeons Pakistan, Regional Centre, Islamabad, Pakistan, from April 2014 to April 2015. METHODOLOGY Sixteen female rats (Sprague Dawley) were selected by random sampling method. Rats were mated and divided into control group A and experimental group B. From gestational day 10 to 18, mother rats received intraperitoneal injection of ethanol (Group B) and normal saline (Group A). Mother rats were allowed to complete their gestation and deliver spontaneously. When pups were born, only male pups were selected for the study. They were reared till day five. At 5ᵗʰ; day, pituitary glands were taken out and histological study was done in PAS-OG stain. Cell count was made in unit area (10,000 μ2) of pars distalis of pituitary gland. Student t-test was applied for analysing the data of cell counts in unit area. RESULTS Mean acidophil count was reduced in experimental group (70.19 ± 11.4) as compared to control group (92.65 ± 8.52, p

The distribution of cell types in the pituitary gland was studied in a consecutive autopsy series of men over 40 years of age. Among 166 individuals, not previously subjected to prostatic surgery or oestrogen treatment, the proportion of PAS-positive cells was higher in men with hyperplasia or neoplasia of the prostate than among individuals showing a histologically normal prostate. PAS-positive cell counts were negatively influenced by several factors related to wasting disease, while acidophil cells apparently increased in conditions of acute and severe stress. Using multiple regression analysis, benign prostatic hyperplasia was selected as the only one among histological diagnoses which significantly reduced the variability of PAS-positive cell proportion, even when the negative influence of other factors had been accounted for. PAS-positive cell counts did not effectively discriminate between the various forms of abnormal prostatic growth encountered. The data presented indirectly give support to the concept of some form of endocrine derangement in the ageing male.

Transsphenoidal adenomectomy was done on 125 acromegalics. A clinicomorphological study was performed on 113 of these patients. The distribution of morphological types of tumors was similar in both sexes. In the total group it was: sparsely granulated GH cell adenomas 52.8%, densely granulated 25.7%, mixed somatotroph and lactotroph adenomas 15.9%, plurihormonal adenomas 1.8%, acidophil stem cell adenomas 2.6%, and oncocytoma 1.8%. The GH plasma level in male patients was significantly higher than in female patients. In both sexes GH secretion was highest in patients with mixed GH and PRL cell adenomas followed by patients with densely granulated GH cell adenomas. Plasma PRL levels were significantly elevated in all males, except for those with densely granulated GH adenomas where prolactinemia was normal. The mean plasma PRL levels were also elevated in females with highest values in mixed somatotroph and lactotroph adenomas. The PRL levels in female patients with densely granulated GH cell adenomas are more elevated than in female patients with sparsely granulated GH cell adenomas.

The present study aimed to evaluate the pharmacological effects of Menoprogen in the management of menopausal symptoms for aged female rats. Menoprogen was supplemented to a group of elderly female rats for 8 weeks. Subsequently, histopathological examinations were conducted in the isolated uterine and ovary tissues and pituitary glands of the rats. Serum levels of estradiol (E(2)), progesterone (P), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined. The ultrastructure of the rat ovarian granulocytes was analyzed. The histopathological examinations revealed no statistical difference in the quantity of follicles in the ovary and of acidophil and basophil cells in the anterior pituitary gland of the Menoprogen-fed rats versus healthy normal rats. Moreover, the cellular morphogenesis was in a healthy state for the Menoprogen-fed rats. Menoprogen significantly increased the levels of serum E(2) and P but reduced FSH and LH levels. The electron microscopic analysis showed that Menoprogen significantly retarded apoptosis of the ovarian granulocytes of the rats. Further investigation of Menoprogen for the alternative treatment of menopausal symptoms is warranted.

Orexins-A and -B are hypothalamic peptides derived from a precursor called prepro-orexin and relationated with the stimulation of food intake. They act on G protein receptors named orexin receptor 1 (OX(1)R) and orexin receptor 2 (OX(2)R), respectively. In the present study, we used RT-PCR and immunohistochemical techniques to detect the presence of OX(1)R and OX(2)R in human pituitary. A band of the expected size for both OX(1)R and OX(2)R was shown in human pituitary by RT-PCR. The cellular localization of OX(1)R and OX(2)R was carried out using histological techniques. By consecutive sections we demonstrated that OX(1)R was present in acidophil, diffusely distributed cells, which represent the half of the total adenohypophysis cell population. As was expected, these cells were shown to coexpress GH. OX(2)R was found in the pars intermedia and in clusters of basophil cells of the anterior pituitary, which coexpress ACTH. These results were confirmed by double immunofluorescence techniques. We also found focal positivity in axon terminals of neurohypophysis, more intense for OX(2)R than for OX(1)R. In conclusion, these results demonstrated for the first time that OX(1)R and OX(2)R were expressed by somatotrope and corticotrope cells, respectively.

A study was conducted to assess pathological changes in endocrine glands induced by 1 and 1.5 ppm dietary levels of aflatoxin (AF) in Athulya layer birds fed for 21 days. The control and AF fed layer birds did not show any clinical signs and mortality except for irregular areas of calcium deposits on egg shell surface. The histopathological alterations included basophil depletion and acidophil prominence in the pituitary and diffuse capsular thickening, hypercellularity of cortical areas and multiple cytoplasmic vacuolation of cortical cell in adrenal glands. The sections of thyroid gland showed pale and thinner colloid mass in the follicles and interfollicular congestion. The histopathological alterations in the present study could be attributed to indirect hepatotoxicity of AF.

Growth hormone(GH)-producing pituitary adenomas are morphologically heterogeneous and frequently contain not only GH immunoreactivity but also variable numbers of prolactin (PRL) immunopositive cells. Paraffin sections of 59 surgically removed GH- and/or PRL-producing adenomas classified by histology, immunocytochemistry (ICC) and electron microscopy were studied using in situ hybridization (ISH) for GH and PRL mRNA and combined with ICC for the coded hormones. Somatotroph adenomas (10 densely and 10 sparsely granulated tumours) and mammosomatotroph adenomas (10 cases) contained both GH mRNA and GH immunoreactivity. In 4 densely and 4 sparsely granulated somatotroph adenomas and 4 mammosomatotroph adenomas, only GH mRNA and its product were found. In 28 cases (6 densely and 6 sparsely granulated somatotroph adenomas, 10 mixed somatotroph-lactotroph adenomas and 6 mammosomatotroph adenomas) both GH and PRL mRNA were present, although no PRL immunoreactivity was not in 2 densely granulated somatotroph adenomas. In these cases, ISH for PRL mRNA combined with GH immunostaining revealed the presence of variable numbers of mammosomatotrophs. In 9 acidophil stem cell adenomas only PRL mRNA and its product were found; one tumour expressed both GH and PRL mRNA and their products. Nine lactotroph adenomas contained only PRL mRNA and PRL immunoreactivity. The results show that GH and/or PRL mRNA content could not be correlated with ICC for coded proteins and ultrastructural features. The mammosomatotrophs were more numerous using ISH when compared with ICC. Somatotroph, mammosomatotroph and mixed adenomas are closely related and they can be considered to represent one basic tumour type originating in a cell committed to GH production. This may undergo clonal differentiation towards a mammosomatotroph and further to the lactotroph line. The results also indicate that lactotroph adenomas arise in a cell committed to PRL production. Acidophil stem cell adenomas seem to be more closely related to lactotroph cells than somatotroph.

Insulin-like growth factors(IGF) are involved in feedback regulation of growth hormone(GH) secretion from the pituitary. Though receptors for IGF-I and IGF-II have been identified on particulate preparations of rat pituitary, their localization and relationship to GH-secreting acidophils has not been determined. We used quantitative in vitro autoradiography and immunocytochemistry to simultaneously determine the distribution of IGF receptors and GH-secreting cells in human infant pituitary gland. Frozen or fixed post-mortem human infant pituitary glands were sectioned for binding studies, or immunocytochemistry. Binding for IGF-I and IGF-II showed characteristic specificity for respectively Type I and Type II receptors. Binding sites were visualized throughout the pituitary gland, with similar density and distribution for IGF-I and IGF-II receptor sites. Receptor density was two-fold higher in anterior than posterior pituitary, with highest density in the lateral horns of the anterior pituitary. The distribution of GH-containing cells (acidophils) was similar to IGF receptor distribution. Increased density of IGF receptors in regions of GH-secreting cells may point to the mechanism whereby IGF uniquely inhibits synthesis of human GH in contrast to its promotion of synthetic processes in other cells.

The progression from nonpregnancy through late lactation is associated with an increase in the proportion of anterior pituitary cells that secrete PRL and a comparable decrease in the percentage of cells that release GH. These fluctuations result from variations in both the number of cells that release GH or PRL alone and mammosomatotropes, cells that release both hormones concurrently. However, it has not been determined whether this reciprocal shift in PRL and GH secretors during the onset of lactation is readily reversible. In the present study, anterior pituitaries from adult virgin, late lactating, or postweaning female rats (4, 6, or 8 days) were dispersed with trypsin and subsequently assayed for PRL and GH release using reverse hemolytic plaque assays. We found that separating lactating females from their pups for only 4 days induced a reciprocal shift in the proportions of GH and PRL cells back to levels found in virgin females. Simultaneous plaque assays were then performed to determine whether this post-weaning shift in the percentages of GH and PRL secretors was due to changes in the abundance of cells that secrete each hormone alone or in the proportion of mammosomatotropes. The overall changes in GH and PRL cell proportions consisted of variations only in the fraction of cells that secreted either GH or PRL alone; no differences were observed in the percentage of mammosomatotropes or in the overall abundance of acidophils. Our results demonstrate that the reciprocal shifts in the proportions of PRL- and GH-secreting cells associated with lactation are rapidly reversible. Moreover, these results are consistent with our hypothesis that PRL and GH secretors are functionally interconvertible and further suggest that this process is bidirectional.

Estrogen (E2; estradiol) plays a key role in the regulation of many pituitary hormones. It exerts its effects by binding to the intracellular estrogen receptor (ER), which then functions as a transcription factor. Although E2 has been shown to regulate calbindin-D(9k) (CaBP-9k) in the female reproductive system of rodents, the effects of E2 on the regulation of CaBP-9k in male rats remain to be elucidated. To investigate E2-induced regulation of the pituitary CaBP-9k gene, immature male rats were injected with E2 daily for 3 consecutive days with a dose of 40 microg/kg body weight (BW). The expression levels of CaBP-9k mRNA and protein were analyzed by RT-PCR and Western blot analysis, respectively, in the absence and presence of ICI 182,780 (ICI), an E2 antagonist. In addition, the tissue localization of CaBP-9k was determined by immunohistochemistry. CaBP-9k was localized in the cytoplasm of a specific cell type (acidophils) in the anterior lobe of the pituitary gland and highly expressed in the intermediate lobe. Exposure to E2 increased the number of cells that stained positive for CaBP-9k. To determine which ER subtype is involved in CaBP-9k regulation in the pituitary, the immature rats were treated with propyl pyrazole triol (PPT, an ERalpha-selective ligand) or diarylpropionitrile (DPN, an ERbeta-selective ligand) for 3 days. Pituitary CaBP-9k expression was mainly mediated by PPT in immature male rats, whereas no significant alteration of pituitary CaBP-9k gene expression was observed after DPN treatment. In addition, the estrogenicity of PPT in the induction of CaBP-9k expression was completely blocked by an estrogen antagonist, ICI, indicating that pituitary CaBP-9k expression is solely induced by ERalpha. Taken together, these results suggest that pituitary CaBP-9k is induced by E2 in male rats and its expression is predominantly regulated by ERalpha, but not ERbeta.

Summary Pituitary glands of normal-termed stillborn goat kids with congenital goitre and normal-termed stillborn goat kids without congenital goitre were examined macroscopically, histopathologically and immunohistochemically. Thyroid glands of these animals were also examined grossly and microscopically. The pituitary glands of kids with goitre were larger than those of normal kids, and on histopathological examination there was hyperplasia of the acidophil cells in the ventral part of the glands. However, it was impossible to distinguish thyroid stimulating hormone (TSH)-secreting cells from other acidophil cells in sections stained with haematoxylin and eosin (HE). Red granules were observed in the cytoplasm of these hyperplastic cells in periodic acid-Schiff (PAS)-stained sections. Sections were also immunostained with an antibody against TSH using the streptavidin–biotin peroxidase technique. Immunohistochemistry revealed TSH-secreting cells to have increased in number in the pituitary glands of kids with congenital goitre because of the extensive proliferation when compared with those of normal kids. The present study indicated that the presence of multiple fetuses (twins or triplets) may be a predisposing factor for congenital goitre.

Insulin-like growth factors (IGFs) have been reported to promote cell proliferation in many tumours, but their contribution to pituitary adenoma development and growth has not been characterized. We report the presence of insulin-like growth factor II (IGF-II) mRNA in pituitary adenomas using in situ hybridization (ISH). The intensity of IGF-II hybridization signal was correlated with adenoma type, and the presence of Ki-67. Among the 109 adenomas examined, 55 (50.4%) were positive for IGF-II mRNA. All acidophil stem cell, functioning corticotrophic and plurihormonal adenomas contained the message; a high incidence of signal was found among sparsely (7/8) and densely (4/6) granulated growth hormone (GH) cell adenomas, mixed GH cell-prolactin (PRL) cell adenomas (6/7), thyrotrophic (4/6) and null-cell (6/7) adenomas. Less frequently, IGF-II mRNA was localized in mammosomatotrophic, silent subtype 3, gonadotrophic, and oncocytic adenomas, whereas all sparsely granulated PRL cell adenomas and silent corticotrophic adenomas of subtypes 1 and 2 were negative. The MIB-I labelling index was significantly higher in adenomas with a moderate to intense IGF-II signal than in adenomas with weak or no signal. The results suggest that IGF-II, when highly expressed, may have a role in pituitary adenoma proliferation.

Age-related changes in the numbers of mammotrophs, somatotrophs, mammosomatotrophs, and the cells of other types in the anterior pituitary of female Wistar rat were measured by flow cytometry. The mammotrophs increased with age, and the somatotrophs decreased with senescence. The mammosomatotrophs increased remarkably in senescent rats, and these cells of the rats older than 21 months were about 10 times more than those of 3, and 12-13 months old rats. This result indicates that the stability of gene expression in cell differentiation is reduced in the aging process of the anterior pituitary.

Estrogen receptor (ER) was demonstrated in nontumorous and adenomatous human pituitaries by autoradiography and biochemical assays. In the present study, we investigated ER mRNA by in situ hybridization applied on paraffin section of 9 nontumorous pituitaries obtained at surgery or autopsy and 109 surgically removed adenomas. In nontumorous pituitaries, in situ hybridization combined with immunocytochemistry revealed hybridization signal in GH-, PRL-, ACTH-, TSH-, and LH/FSH-immunoreactive cells, with the highest intensity in PRL-immunoreactive cells. ER mRNA was also localized in Crooke's cells, corticotrophs extending to posterior lobe, cells lining the pars intermedia cavities, and squamous nests of pars tuberalis. The neurohypophysis, endothelium, and connective tissue expressed no ER gene. ER mRNA was present in all adenoma types, including somatotroph, lactotroph, mixed somatotroph-lactotroph, mammosomatotroph, acidophil stem cell, functioning and silent corticotroph, thyrotroph, gonadotroph, null cell adenomas, and oncocytomas. The strongest signal was seen in some lactotroph and mammosomatotroph adenomas. In 9 lactotroph adenomas exposed to bromocriptine (long-acting repeatable injectable form), the hybridization signal was weak or absent, suggesting that suppression of ER gene plays a role in the inhibition of PRL synthesis and tumor growth.

I. Introduction MORE than a half century has passed since Romeis first proposed the “one cell-one hormone” theory which holds that each of the major pituitary hormones is produced by a separate and distinct cell type (1). Consistent with this idea, the acidophilic staining cells (termed acidophils) of the adenohypophysis have been traditionally subdivided into two categories, those that secrete only GH and others that produce just PRL. This view was supported by considerable tinctorial evidence available at the time of Romeis' hypothesis and generated in the subsequent three decades (1–5). Moreover, data produced throughout the 1970s and early 1980s by the use of light microscopic immunocytochemistry (ICC) and immunofluorescence were generally consonant with the one cell-one hormone theory, except in the case of certain pituitary tumors (6–8). The presence of bihormonal acidophils in this latter situation was attributed to aberrant mechanisms attendant to the neoplastic condition. However, as will be disc...

Estrogen (E2; estradiol) plays a key role in the regulation of many pituitary hormones. It exerts its effects by binding to the intracellular estrogen receptor (ER), which then functions as a transcription factor. Although E2 has been shown to regulate calbindin-D9k (CaBP-9k) in the female reproductive system of rodents, the effects of E2 on the regulation of CaBP-9k in male rats remains to be elucidated. For investigation of E2-induced regulation of the pituitary CaBP-9k gene, immature male rats were injected with E2 daily for three consecutive days with a dose of 40 µg kg–1 body weight (BW). The expression levels of CaBP-9k mRNA and protein were analyzed by RT-PCR and Western blot analysis, respectively, in the absence and presence of ICI 182 780 (ICI), an E2 antagonist. In addition, the tissue localization of CaBP-9k was determined by immunohistochemistry. CaBP-9k was localized in the cytoplasm of a specific cell type (acidophils) in the anterior lobe of the pituitary gland and highly expressed in the intermediate lobe. Exposure to E2 increased the number of cells that stained positive for CaBP-9k. For determination of which ER subtype is involved in CaBP-9k regulation in the pituitary, the immature rats were treated with 1 mg kg–1 BW propyl pyrazole triol (PPT, an ER-α-selective ligand) or diarylpropionitrile (DPN, an ER-β-selective ligand) for three days. The data were analyzed by the non-parametric procedure of the Kruskal-Wallis test, followed by Dunnett's test for two-pair comparisons. Pituitary CaBP-9k expression was mainly mediated by PPT in immature male rats, whereas no significant alteration of pituitary CaBP-9k gene expression was observed after DPN treatment. In addition, the estrogenicity of PPT in the induction of CaBP-9k expression was completely blocked by an estrogen antagonist, ICI 182 780, indicating that pituitary CaBP-9k expression is solely induced by ER-α. Taken together, these results suggest that pituitary CaBP-9k is induced by estrogen in male rats and its expression is predominantly regulated by ER-α, but not ER-β.

The pituitary gland of the ricefield eel, Monopterus albus is made up of the neurohypophysis, which form the central core, and the adenohypophysis, which completely surrounds the former except at the infundibular connection. Pituitaries, in longitudinal and transverse serial sections, lave been studied by standard histological and histochemical techniques including Periodic acid-Schiff(PAS)/Celestine blue (CB)/Orange Gy- (OG), Herlant's tetrachrome (HT), Lead haematoxylin (PbH)/PAS, Aldehyde Fuchsin (AF), Luxol fast blue (LFB)/PAS/OG, Alcian blue (AB, pH 0.2 and pH 3.0)/PAS/OG, and Aldehyde Thionine (AT)/PAS/LFB. Seven tinctorial cell types are distinguishable in the adenohypophysis: the erythrosiniphilic and PbH-positive amphiphil (Type 1); erythrosinophilic acidophil (Type 2); orangeophilic acidophil (Type 3) ; PbH-positive acidophil (Type 4) ; very intensively AF-positive, AB-positive and AT-positive basophil (Type 5) ; weakly AF-positive, AB-positive and AT-positive basophil (Type 6) ; strongly AF-positive, AB-positive and AT-positive (Type 7). Chromophobes which show no affinity for any of the above stains are also found. The neurohypophysis shows extensive interdigitations and staining with AF, AB and AT indicates that the neurosecretion is concentrated towards the distal end of the neurohypophysis. Blood capillaries are found in abundance both in the adenohypophysis and in the neurohypophysis. The present report is the first in the series of studies on the role of pituitary in natural sex reversal in Monopterus and provides the basic information on the pituitary cytology and structure for further experimental and biochemical investigations which are reported separately.

The complement fixation immunoassay (CFIA) was used for quantitating growth hormone (GH) in crude anterior pituitary extracts from rats subjected to thyroidectomy with or without cortisol and exogenous GH administration. The results obtained from this study were compared with pertinent bioassay (tibia test) results or correlated with the pituitary acidophil cell counts. Whereas it has been reported that pituitary GH levels are normal by the tibia test at 2 weeks after thyroidectomy, the highly specific CFIA method showed an actual 87 % decrement which correlated well with the reduction in acidophils. In addition, the apparently normal content of GH after cortisol administration to thyroidectomized rats, as measured by the tibia test, was contradictory to the very low acidophil population and to the marked reduction in pituitary GH content as measured by the CFIA. Furthermore, theoretical tibia responses illustrate the inconsistency of the bioassay in different experimental conditions. If, as previously suggested, the content of thyrotrophin (TSH) in the crude pituitary extracts renders the bioassay of GH a dubious procedure, then the superiority of immunoassay is obvious.

This review discusses the pathophysiology of acromegaly. Acromegaly has been classified in this paper into distinct entities based on etiology, ultrastructural features of the pituitary, and cytogenesis. This classification has been proposed based on clinical signs, immunoperoxidase techniques, transmission electromicroscopy and immunoelectron microscopy. Pituitary causes of acromegaly include densely granulated adenomas, sparsely granulated adenomas, mixed growth hormone and prolactin cell adenomas, acidophil stem cell adenomas, mammosomatotroph cell adenomas, and pleurihormonal adenomas. GH cell hyperplasia and GH cell carcinoma are also discussed. Extrapituitary causes of acromegaly include eutopic GH cell adenoma in the sphenoid sinus or parapharyngeal region and excess GHRF secretion which may be eutopic or ectopic. The pathological, clinical, and biochemical evidence in favor of a pituitary or hypothalamic etiology of acromegaly has been reviewed. Finally, a multistage theory of GH cell tumorigenesis has been proposed as a model in an attempt to unify the genetic, environmental and biochemical factors implicated in the pathogenesis of acromegaly.

Fine structural criteria for identifying thyroid-stimulating hormone (TSH) cells in immature and mature rats have been studied by a modified superimposition technique. On days 10 and 20, some small oval immature TSH cells are scattered individually throughout the glandular tissue with a peripheral immunoreactive rim resulting from the sparse distribution of minute secretory granules less than 50 nm in diameter. The immunostained stellate TSH cells are clustered and have secretory granules 50-100 nm in diameter at the cell margins. On day 60, a few small immature TSH cells still remain. Although a few polygonal TSH cells that may not fully mature accumulate secretory granules 100-150 nm in diameter at the cell margins, the majority of TSH cells take the form of large stellate cells filled with secretory granules with the corresponding diameter, and surround an acidophil. These stellate TSH cells are characterized by dense arrangement of parallel arrays of rough endoplasmic reticulum (rER) or rER cisternae. The clustered or isolated elongate TSH cells are also observed to be vesiculated and to have numerous secretory granules 150-250 nm in diameter. In addition, large oval vesiculated TSH cells storing numerous secretory granules 150-250 nm in diameter appear sporadically in the gland, ultrastructurally resembling the gonadotrophs. It is concluded that the rat TSH cell is not a single type with a particular ultrastructure, but modifies its morphology according to its maturation or functional phase.

Isolated pituitary cells from 14-day-old female, 14-day-old male, and adult male rats were separated into several fractions by unit gravity sedimentation. With preparations from 14-day-old animals, the percentage of basophils increased from top to bottom of the gradient. The bottom fractions contained large basophils with a purity attaining almost 90% in the female and 75% in the male preparation. The same fraction prepared from adult male rats was composed of over 80% of large acidophils. As identified by immunostaining, the majority of the female large basophils were gonadotrophs, whereas in 14-day-old males about 1/3 of these basophils were thyrotrophs. The relative proportion of medium and small sized gonadotrophs and of thyrotrophs was also higher in the 14-day-old rats than in the adults. An estimate of the distribution of FSH and LH among the gonadotrophs was made by comparing the number of cells reacting with anti-FSH, with anti-LH, and with a mixture of both antisera. The data suggested that irrespective of cell size, the majority of the gonadotrophs in 14-day-old rats contained both FSH and LH. In most fractions, the occurrence of cells with only one hormone was more apparent in the males than in the females. In adult rats, cells with only FSH were most abundant in the fraction with large gonadotrophs. The distribution of hormone content, as measured by RIA, was highly characteristic for each animal group. In 14-day-old females, more than 70% of the recovered hormones was in the large gonadotrophs. In 14-day-old and adult males, substantial amounts of hormone were also recovered from medium sized gonadotrophs. The present findings suggest a relationship between developmental changes in pituitary hormone secretion and changes in pituitary cell type distribution.

The effect of salts on the pars distalis of R. cyanophlyctis was studied by placing them in sodium chloride, potassium chloride (0.5%), distilled water and tapwater (control) for 15 days. In frogs kept in NaCl solution basophil type 3 cells (B3) showed marked hypertrophy and degranulation, whereas the B3 cells of frogs kept in KCl solution showed the hypertrophy and accumulation of secretory granules inside their cytoplasm. The B3 cells of frogs kept in distilled water or tapwater showed no changes. The other cell types of the pars distalis (A1 and A2 acidophils; B1 and B2 basophils) remained unaffected. It is concluded that the B3 cells are the probable source of adrenocorticotrophin and that the adenohypophyseal hormone(s) play a role in the maintenance of water and salt balance in R. cyanophlyctis.

Prolactin (LTH) and growth hormone (GH) containing cells in A. guldenstaedti have been localized by means of anti-ovine prolactin and anti-bovine growth hormone respectively, coupled indirectly to peroxidase, and localized histochemically with hydrogen peroxide as substrate and 3,3′-diaminobenzidine as capturing agent. The distribution of the anti-prolactin positive cells has been demonstrated and correlated histologically with the acidophilic cells both in the rostral and proximal pars distalis. This cell type is elongated and arranged in follicles in the rostral pars distalis; in the proximal pars distalis they are smaller and oval, without any special orientation. Neither of the other cell types which are scattered among these acidophils contain prolactin. The anti-bovine growth hormone positive cells are evenly distributed in the proximal pars distalis above the hypophysial cleft, and some are also found in the pars intermedia. The anti-GH positive cells have been correlated histologically with the amphiphilic cells in the proximal pars distalis. These cells are arranged in cell cords in close contact with the secondary capillary plexus, near its origin from the primary capillary plexus covering the median eminence.

The induction of pathologic changes with hormone steroids has been studied in rodents, although comprehensive studies are lacking on the potential reversibility of these lesions. For these purposes, groups of rats were treated with quingestanol acetate and quinestrol, a progestogen-estrogen combination, for 50 weeks and observed for a subsequent 30-week period. Treatment resulted in a significant body weight gain suppression and reduction of food consumption which recovered after withdrawal. Other significant treatment-related effects were hair loss, ataxia due to pituitary enlargement, mammary chain masses with histologic adenocarcinoma, lens opacities, ovarian atrophy with follicular arrest, and uterine atrophic changes with suppurative inflammation throughout 50 weeks. Cessation of treatment did not effect hair loss or lens opacities, while mammary chain masses decreased in size and in incidence; mammary gland tumors showed regressive changes including the disappearance of adenocarcinoma, and the incidence of ataxia diminished together with reduced pituitary weights. Chromophobe cell hyperplasia with decreased eosinophils and acidophils and hemorrhage into the pituitary was observed up to 50 weeks and the tinctorial affinity of basophils and acidophils returned after withdrawal. Ovaries and uteri, which become atrophic and sustained chronic suppurative inflammation in the treatment phase, showed reduction of inflammatory reaction and disappearance of suppuration after withdrawal, and endometrial regeneration occurred with luteal cells seen in the ovaries. These results revealed the regressive characteristics of some of the mammary gland carcinomas as well as steroid-induced endocrine and pathologic lesions other than tegumentary and ocular changes in rats receiving high levels of steroids for prolonged periods of time.

The process of development of thyroidectomy (TX) cells from the so-called thyrotrophs (the H-type cells by Yoshimura et al., 1977) was electron-microscopically investigated at intervals of 12 hr, 1, 3, 5, 7 and 14 days after TX. Cytological changes of the II-type cells vary from cell to cell even at the same intervals after TX. From 12 hr to 5 days, the II-type cells are characterized by the deprivation of secretory granules and the enlargement of cell size. When extensively degranulated, the II-type cells appear as vesiculated cells with a round or oval shape, resembling the LH-gonadotrophs (the III-type cells). The frequent detection of III- and IV-type cells (FSH-gonadotrophs) is in striking contrast with the infrequent detection of IItype cells within 12 hr and 1 day. Some pre-existed IV-type cells show retrogressive signs after TX. Some other IV-type cells are moderately granulated, at 1, 3 and 5 days, followed by the deprivation of the stored secretory granules, resulting in the vesiculated cells. These cells begin to appear at 3 days and increase in number at 5 and 7 days, despite the individual disparity in development. They may be the immature TX-cells characterized by the closure of Golgi lamellae, and by granules of low density in the small, irregularly shaped cisternae. They gradually increase in dimensions with the lapse of time. Degranulation and accumulation of large cisternae with progressive sedimentation of intracisternal granules may account for the maturation of TX-cells. By 14 days the maximal diameter of the mature TX-cells becomes 3-4 times as large as that of an acidophil. From the present observations, it is tentatively concluded that TX cells may not directly develop from the II-type cells, but indirectly through the III- or IV-type cells; and that the TX-cells may not be hyperfunctioning thyrotrophs, but rather dysfunctioning basophils.

The pituitary gland of Latimeria chalumnae is situated rostroventral to the telencephalon. The hollow pituitary stalk is bent forward and is ventrally connected to a saccus-vasculosus-like organ, rostrally to a neurointermediate lobe. The infundibular lumen protrudes far into the neurohypophysial lobules. The elongated principal part (pars cerebralis) of the pars distalis is partly embedded in a dorsal depression of the pars intermedia and caudally invaded by the neurohypophysis. It may be divided into rostral and proximal pars distalis and includes a ramified hypophysial cleft, which continues rostrally as a duct with adjacent islets of pars distalis tissue (parts of a pars buccalis). The adenohypophysis consists of cell cords and follicles. Eight tinctorial cell types can be distinguished: in the rostral islets: large basophils with acidophil globules, in the rostral pars distalis: small basophils, large basophils with amphiphil characters and erythrosin-, orange G-positive acidophils; in the proximal pars distalis: orange G-positive acidophils and small and large basophils, having similar staining properties; in the pars intermedia: one amphiphil cell type.

Endocrine glands of the ironfish were studied light microscopically to elucidate the relationship between the races of the genus Carassius. The rostral pars distalis of the adenohypophysis consists mainly of acidophils corresponding to prolactin cells and lead-hematoxylin positive cells corresponding to corticotrophs (ACTH cells). The prolactin cells are obviously arranged in the form of follicles. The proximal pars distalis contains orangenophils (STH cells) and two types of basophils (TSH and GTH cells). In the pars intermedia, three types of cells are identified: periodic acid Schiff positive cells, lead-hematoxylin stainable cells and orangenophils containing PAS positive coarse granules. In addition, small agranular cells are seldom demonstrated in the entire adenohypophysis. A considerable amount of aldehyde fuchsin positive neurosecretory material is laden in the cells of the nucleus preopticus and in the pars nervosa. The nucleus lateralis tuberis is composed of three portions: pars anterior, pars posterior, and pars lateralis. The thyroid follicles found in the pharyngeal region and head kidney show a mild state of activity. The interrenal cells intermingled with the chromaffin cells have a considerable amount of eosinophil cytoplasm. Judging from the gonadal condition, the breeding season of the ironfish may extend to the end of July.

Since its clinical description in the last century, much progress has been made in our understanding of acromegaly. From an initial description of pituitary enlargement as just another manifestation of generalized visceromegaly, the pituitary abnormality has come to be recognized, in most instances, as the underlying aetiological factor. Gigantism and acromegaly are manifestations of disordered pituitary physiology, but the lesion responsible may be hypothalamic, adenohypophyseal or ectopic in location. The best known pathological hypothalamic basis for acromegaly is represented by a neuronal malformation or 'gangliocytoma'. It usually takes the form of an intrasellar gangliocytoma or, more rarely, a hypothalamic hamartoma. The neuronal elaboration of GHRH may play a role in the development of a growth hormone adenoma; the pituitary process may pass through an intermediate stage of somatotropic hyperplasia. When acromegaly has its basis in a pituitary abnormality, the lesion is almost exclusively an adenoma; the non-tumorous adenohypophysis shows no evidence of coexistent hyperplasia. Surprisingly, such tumours are more often engaged in the formation of multiple hormones rather than GH alone. They frequently produce not only GH and prolactin, the products characteristics of cells of the acidophil line, but also glycoprotein hormones, usually TSH. The spectrum of adenomas also varies in its degree of differentiation from a histogenetically primitive lesion, the acidophil stem cell adenoma, to well-differentiated tumours of varying cellular composition and hormone content. Each adenoma type has its clinicopathological, histochemical, immunocytological and ultrastructural characteristics. The isolation and characterization of GHRH has permitted the identification of neuroendocrine tumours, most of foregut origin, elaborating this releasing hormone. Such functional tumours induce hyperplasia of pituitary somatotrophs and may, on occasion, result in the formation of growth hormone adenomas. Resection of these GHRH-producing neoplasms results in reversal of endocrinological and sellar abnormalities. Future efforts should be directed toward the elucidation of the aetiology of pituitary adenomas, specifically whether they represent a proliferative process having its origin in endocrinological imbalance, presumably a hypothalamic abnormality, or whether it has a 'de novo' origin in the 'usual process of neoplastic transformation'.

In our electron microscopy, acidophils in the pituitary autografts placed in the renal capsules of immature male rats underwent a sequential transformation with the lapse of time: Within 3 and 6 days, all the somatotrophs packed with the large granules of about 350mμ diameter dispersed. The size and number of the granules in somatotrophs were quickly and markedly reduced with severe modification of cell shape. There was evidence during this time course that Siperstein's or Moriarty's corticotrophs might be synonymous with the stellate shape of acidophils with the arrangement of small granules 150-200mμ in diameter along the cell membrane. In other word, they may belong to a step of degranulation process of acidophils. The “acidophils of the small granule type” possibly related to ACTH production according to Yoshimura et al.(1974) were frequently detected in the grafts as elongated or irregularly shaped cells. Their minute granules 100-150mμ in diameter were also distributed in row in the cytoplasmic peripheral area. Gradual loss of the minute granules below 100mμ in diameter eventually made the acidophils to transform into agranular cells. Our own idea that ACTH secretion might correlate with a series of cells transforming along the acidophil-axis was indirectly supported by the present observation on pituitary grafts. On the other hand, basophils rapidly degenerated and died away. Ten and 20 days after autografting, the graft cells which might be principally composed of the cells of acidophil origin enormously proliferated through mitotic division, showing the homologous fine structure, without the normal cell individuality. They always contained three different size and shape of granules simultaneously. Significance of such a rapid and strong response of acidophils to the ectopic replacement in the immature male rats was discussed from the view-point of hypothalamic regulation to simple protein hormones.

The indirect immunofluorescence procedure was used to localize prolactin (PRL)- and somatotrophin (STH)- producing cells in the pituitary distal lobe from Hyla arborea adult specimens. The following mammalian antisera were employed: rabbit anti-ovine PRL, antibovine PRL, anti-human PRL, anti-rat PRL, anti-ovine STH, anti-bovine STH, anti-human STH; monkey anti-rat STH. Immunocytochemical staining was suppressed by solid phase absorption of both anti-PRL and anti-STH with the specific antigen. Absorption of anti-PRL with STH and of anti-STH with PRL did not appreciably affect immunocytochemical staining. Treatment with the two antisera revealed two different reactive cell types, both acidophils. Using PRL antisera a strong fluorescence was found in the large acidophils located chiefly in the rostro-central and ventral areas of the distal lobe sagittal sections. A somewhat weaker fluorescence was observed using STH antisera in the fewer, small acid-ophils mostly concentrated in the dorso-caudal region and only sparsely scattered in the other areas of the pars distalis. Strikingly, the overall pattern of localization shown by the two cell types is similar to their already known distribution in the pituitary distal lobe of some other species of urodele and anuran amphibians.

When cryostat sections of endocrine tissue were examined in a dark-field microscope, a brillant granular luminescence was revealed in the endocrine cells thought to be concerned with protein or polypeptide horome production. The sections were prepared from fresh materials either frozen in a cryostat chamber at --25 degrees C, in dry ice-acetone, or fixed in formalin-calcium for 24 hr. The neurosecretory substance in the hypothalamus and the posterior lobe of the pituitary showed a blue luminescence; the acidophil cells of the anterior lobe of the pituitary, orange; basophile cell, green or blue; intermediate lobe cells, no luminescence; thyroid C cells, white-blue; pancreatic A cells, blue; B cells, orange; adrenomedullary cells, greenish blue; enterochromatin cells, green; and other endocrine cells in the gastrointestinal tract, blue or orange. After tearing and spreading the pituitary and hypothalamus with a pair of needles on a glass slide, and examining the teased specimen by dark-field microscopy, various cells of different lumunescent colours became apparent in the anterior lobe of the pituitary, a blue fluorescent substance in the posterior lobe, and neurosecretory cells bodies in the hypothalamus. The different colours appear to be inherent in the granules of living tissues.

In order to verify the concept that growth hormone and prolactin are contained in two different populations of acidophils, sections of Bouin-fixed rat hypophyses were stained immunochemically. For this purpose the histochemical demonstration of peroxidase was utilized after sequential application to the tissue section of rabbit antiserum to human growth hormone (or antiserum to rat prolactin) followed by application of peroxidase-labeled sheep antiserum to rabbit gamma-globulin. It was found that growth hormone cells and prolactin cells, when revealed immunochemically, corresponded structurally to cell types that could be differentiated with reasonable certainty in sections stained with the Masson trichrome procedure. When delineated immunochemically, growth hormone cells were larger and more densely arranged in the adult male than in the intact female; they exhibited little change in the female after ovariectomy. In contrast, prolactin cells were large and frequent in the female hypophysis but were small and less frequent in the male and in the female after ovariectomy. By double-staining, growth hormone and prolactin cells were differentiated in the same section. It was concluded that (a) growth hormone and prolactin are contained in, and presumably secreted by, two different populations of acidophils; and (b) the Masson procedure permits a reasonably accurate differentiation of the two cell types.

The original source of thyroidectomy cells (TX-cells) in rats was investigated electron microscopically. Thyrotrophs did not respond so definitely to thyroidectomy as gonadotrophs did to castration. In thyrotrophs, changes in terms of hyperplasia, hypertrophy and de-or hypergranulation were not manifested. There was no evidence that TX-cells belonged to hyperactive thyrotrophs. The course of transformation from the degranulated acidophils to TX-cells was clearly demonstrated in sequence in this study. Hypertrophy, deformation of the cell, expansion of cisternae, occurrence of intracisternal granules and enlargement of the Golgi-ring, these were manifestations of the developmental process of degranulated acidophils into TX-cells. The other process of transformation of acidophils into TX-cells seemed related to the gradual dilation of ER without discharging their large granules completely. During the chronic phase of thyroidectomy, the anterior pituitaries were filled with TX-cells and their precursors. High vesiculation could be considered as an intrinsic biological reaction which is commonly seen in most of hypophyseal cells during thyroxine deficiency. It was, therefore, suggested that degranulated or slightly granulated acidophils might be predominantly the original sources of TX-cells. Thus, the acidophil theory has been firmly established as to the genesis of TX-cells. We, at the same time, wanted to open up a possibility that some TX-cells might arise from immature basophils, but the valid evidence was not produced in this study. It was verified electron microscopically that the fully developed round TX-cells seemingly like signet-ring-typed castration cells were quite different from genuine castration cells, although both cells had the same staining properties and light microscopical characteristics. However, a number of immature gonadotrophs came into being during the chronic phase of thyroidectomy.

The pituitaries of female rats subjected to various alterations in thyroid function were examined for changes in hypophyseal growth hormone content and acidophil morphology. Thyroidectomy caused a significant decrease in the amount of growth hormone as well as a decrease in the acidophil granulation and population, whereas subsequent treatment with thyroxine allowed the pituitary structure and growth hormone content to return to normal. The pituitaries of unoperated rats fed a diet containing thyroid powder contained less growth hormone than those from normal controls, and the population and granulation of the pituitary acidophils were decreased. The pituitary growth hormone content of thyroidectomized rats fed a diet containing 2,4-dinitrophenol was increased above thyroidectomy levels, but neither the pituitary cytology nor the hormonal level was restored to normal. The same diet fed to unoperated rats did not significantly alter the pituitary growth hormone levels and structure.

A histological and histometrical estimation was made on the adenohypophyseal cells of bilaterally adrenalectomized adult rats, which were sacrificed at various time-intervals from 6 hours to 32 days. The thyroid weight decreased, then rose again, being stabilized below the normal level after 3 days. The pituitary weight dropped slightly at 3 days, but soon returned to normal. The change in cell-height of the central follicles in thyroids was variable and exhibited no definite tendency. The height of epithelium of the ventral prostate tended to decrease gradually in a straight line. The cell-count resulted in a conclusion that the ranges of acidophils and chromophobes have an early and late peak. A slight decreasing shift was found in gonadotrophs. The curve of thyrotrophs represented a decreasing shift following an initial temporary rise. The population of intermediate cells between the chromophobes and chromophils was so intricate that its significance was hard to determine. The curve, including two peaks, of pituitary ACTH content in rats after adrenalectomy (Gemzell et al., 1951 and Fortier, 1959) was compatible with the population curve of chromophobes and acidophils, but inconsistent with that of the other cell elements. An early degranulation and subsequent accumulation of the α-granules in acidophils might be signs of discharge and secondary storage of the hormonal precursor in acidophils. It was suggested that the axis of the cellular transmigration from a chromophobe into an acidophil is likely to be concerned with ACTH secretion, because the population of chromophobes usually precedes that of the acidophils.

Fluorescein-conjugated antisera to porcine growth hormone localize in acidophils of rat, pig, beef, sheep, and dog pituitaries. Using AT – PAS – orange G stain, two types of acidophils could be distinguished in pig, beef, sheep, and dog pituitaries. Localization of anti-porcine growth hormone was confined to only one acidophil cell type in pituitaries of these species.

The structure and ultrastructure of the meso-adenohypophysis of the viviparous teleost, Cymatogaster aggregata Gibbons are described. One acidophil, one chromophobe and two basophil cell types were identified. Following treatment of the fish with “methallibure”, the gonadotroph basophils were completely, and the somatotroph acidophils partially, depleted of electron-dense granules, whereas the thyrotroph basophils were slightly hypertrophied. The usefulness of “methallibure” as an agent for chemical hypophysectomy in studies of gametogenesis is discussed.

Partial separation of the hormones of the anterior pituitary of beef has been obtained by ultracentrifugation in the Spinco Model L Ultracentrifuge. Fresh and frozen glands were homogenized in 0.25 m sucrose and centrifuged at 500 x g to remove nuclear and cellular debris, at 6600 x g to obtain mitochondria, at 11,150 x g to obtain acidophiles, and at 80,000 x g to obtain basophiles. Each fraction was analyzed for nitrogen, for PNA and for hormonal content. Most of the nitrogen was obtained in the supernatant, most of the PNA in the acidophil granules, and the activity was partially separated. In general the mitochondria contained growth hormones, acidophil granules contained ACTH, supernatant contained FSH, and TSH and LH were found in both acidophil and basophil granules.

Adult male common frogs (Rana temporaria) were exposed to increased temperatures (10 and 26°C) and various tissues and organs were examined histologically two and seven weeks later. Appropriate control tissue was obtained from hibernating animals. The following tissues and organs were examined: pars distalis of the adenohypophysis (acidophils type 1, basophils types 2 and 3); interrenal gland; interstitial tissue (Leydig cells) and germinal epithelium of the testis.

The pituitary gland of the medaka Oryzias latipes consists of three portions: the pars distalis, the pars intermedia and the neurohypophysis. The pars distalis is further divisible into rostral and proximal zones. On the basis of differences in tinctorial and histochemical properties, eight different cell types are distinguished. The rostral pars distalis contains two types of acidophils: one is clearly revealed by acid violet (Type 1, probably cells producing prolactin-like hormone) and the other type is distinguished by lead haematoxylin (Type 2, probably corticotropic cells). The proximal pars distalis contains two types of basophils, probably gonadotropic cells (Type 3) and thyrotropic cells (Type 4), which distinguished from each other by the differences in avidity for dyes, size and location. Further, the proximal pars distalis contains orange G-positive acidophils (Type 5, probably somatotropic cells) and relatively many chromophobes (Type 6). The pars intermedia contains acidophils (Type 7) and basophils (Type 8); the former is lead haematoxylin-and Gomori-positive and the latter is aniline blue-and PAS-positive. The neurohypophysis is roughly divisible into a rostral portion containing mostly Gomori-negative fibers and a caudal portion containing mostly Gomori-positive fibers.

Large amounts of iodide (1 to 5 mg.) were injected into groups of young male rats in which growth had ceased following thyroidectomy. An immediate resumption of growth occurred in all animals and was more vigorous in those receiving the highest levels. The pituitaries of the thyroidectomized rats injected with iodide were distinguishable from untreated thyroidectomized controls by the presence of a few more acidophils and by improvement in those basophils which are considered to be gonadotrophs. There was evidence of improvement in the morphology and function of the Leydig cells of the testes. The atrophic adrenals on the other hand, showed no evidence of repair. The metabolic rates, measured just before autopsy, of all thyroidectomized rats that received iodide were not significantly different from those of untreated thyroidectomized controls. The sensitive chromatographic procedure described in the preceding communication (1) was applied to plasma, plasma digests, and liver digests of both iodide-treate...

The removal of the adenohypophyseal primordium and anlagen of the telencephalon and diencephalon was made in embryos of Rana esculenta at the tail-bud stage. Extirpation of the anlage of the preoptic area resulted in disorders of general development. The effect of this operation resembled that of the removal of the preoptic nucleus in older larvae (absence of metamorphosis and hyperpigmentation). However, the ability for independent feeding and the level of tissue hydrophilia did not deviate from normal significantly. The dependence both of differentiation and function of the main types of secretory cells of the pars anterior upon neurosecretion was shown. High activity of the basophils coincides with an intensive neurosecretion in the hypothalamus, and with hyperemia of the neurohypophysis. Acidophil formation is associated with the beginning of neurosecretory activity in the larva, or with the period of its shrinkage in transforming to the adult frog. If the neurosecretion was fully absent, as a result of experimental intervention, acidophil differentiation appeared to be inhibited and the growth hormone was not produced. Nervous control of the pars intermedia by the hypothalamus occurs independently of the portal vascularization of the adenohypophysis. Either lesions or cuts of the nervous fibers of the hypothalamo-hypophyseal pathway result in hypersecretion of the pars intermedia cells. High neurosecretory activity inhibits the function of the pars intermedia, showing the significance of the humoral mediator in the nervous inhibitory influence on the glandular cells.

Development of acidophils was investigated electron microscopically in pituitaries from the rat embryos on the 15th, 17th, 18th and 20th day of gestation and from the neonatal and postnatal rats on the 1st, 3rd, 4th, 6th, 12th and 18th day of birth. Pituitary agranular primordial cells are the stem cells from which acidophils develop. During embryonic life, the male is more advanced in differentiation of primordial cells than the female. Initial granulation begins to take place in “ambiguous cells” (Yoshimura et al., 1970) on the 17th day of gestation as a row of minute granules about 50 mμ along the plasmamembrane. Incidence of ambiguous cells with various shapes is higher in the male than in the female. During embryonic period, only a small number of immature acidophils have developed from ambiguous cells despite spherical enlargement of cell-bodies where dense granules maintain their size within the proximity of 250 mμ. Most of ambiguous cells tend to transform into immature basophils, and even gonadotroph-like basophils have accumulated during the latest pregnancy. On the other hand many immature acidophils emerge directly from primordial cells without the mediation of ambiguous cells. In a certain primordial cells, a row of dense granules as large as 130-200 mμ in diameter suddenly appear along the plasmamembrane on the 18th day of gestation. In equilibrium with the prompt increase in the cell number, their granules rapidly increase in dimension and their maximal size reaches 250 mμ towards the end of fetal period. Postnatal development of acidophils is quite quick as to the population and granulation in both sexes. Numerous immature acidophils, not always spherical but somewhat elongated, develop appositionally from primordial cells. Appearance of a row of large granules of 200-250 mμ along the plasmamebrane of primordial cells seems to be related to morphological representation for the main developmental process of acidophils. Granules in immature acidophils increase in number, their size being persistently less than 200 mμ up to the 6th postnatal day. Enlarged spherical premature acidophils containing numerous granules of 200-300mμ in diameter begin to appear on the 12th day. So-called somatotrophs identical with the fully developed acidophils filled with large granules of about 350 mμ start to appear on the 18th day of age.

The morphology of an autonomous diethylstilbestrol-induced pituitary tumor (Furth’s tumor MtT-F4) has been studied by light and electron microscopy. This tumor, besides having mammotrophic and somatotrophic activities, exerts an adrenocorticotrophic effect. The cells of the tumors contain minute, faintly stainable granules. In electron micrographs, there is but one type of secretory granule, measuring up to about 350 ran m diameter. It has the same appearance as the acidophil granules of the so-called growth hormone type. The findings are discussed with respect to the possibility that the pituitary gland contains pluripotent cells whose secretion can be differentiated to satisfy functional demands and that this causes them to present morphological characteristics of either basophils or acidophils. (Endocrinology 75: 893, 1964)

The relationship between the distribution of prolactin and the various cell types in the pars distalis (PD) of two species of lizard, two species of snake and a turtle were examined in order to determine the site of prolactin production in the reptilian pituitary. Prolactin was measured by pigeon crop-sac bioassay, and, in the turtle, by polycrylamide gel (disc) electrophoresis. Pigeon crop-sac stimulating activity (prolactin) was observed in the pituitary of all species examined. In every case, most of the hormone was localized in the rostral half of the PD and in the lizards none was detected in the caudal region. Disc electrophoresis verified this finding in the turtle and also suggested that a presumptive growth hormone is concentrated in the caudal half of the chelonian gland. Thus, it appears likely that the lactotropes are located rostrally and the somatotropes caudally in the reptilian PD. Histological studies of the PD demonstrate two types of acidophils which show a marked regional distribution; a carminophil is restricted almost entirely to the rostral half of the PD and an orangeophil to the caudal half. On the basis of patterns of hormone distribution, it seems likely that the rostral carminophil is the lactotrope, and the caudal orangeophil may be the somatotrope.