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Puberty represents a milestone during a person's life and is characterized by several physical and psychological changes which end with the achievement of sexual maturation and of fertility. Puberty onset depends on a series of sophisticated, not completely understood, mechanisms certainly involving Gonadotropin-Releasing Hormone (GnRH) and its effects on pituitary gonadotropins. As recent evidence has demonstrated that pubertal timing deeply affects future adult health life, many efforts have been performed in order to clarify the exact actors involved in the onset and progression of puberty. Genetic factors are undoubtedly essential players in the regulation of pubertal development, accounting for approximately 50-80% of its variability. Mutations in genes such as KISS1, MKRN3, and DLK1 have been associated with central precocious puberty. Interestingly, a possible involvement of epigenetic mechanisms has been proposed as additional element able to affect pubertal phase. Environmental factors have recently attracted much attention. Indeed, an overall decrease in the age of puberty has been observed in the last decades. As genetic factors require long time to exert their effect, other players, such as environmental ones, may be involved. Special focus has been posed on nutritional status, endocrine-disrupting chemicals with non-conclusive results. Pubertal timing deeply affects future life, suggesting the need to clarify mechanisms driving pubertal onset and progression, in order to identify tailored therapeutic strategies and targets.

Background The connection between testicular ultrasound (US) parameters and testicular function, including both spermato- and steroidogenesis has been largely suggested, but their predictive properties are not routinely applied. Radiomics, a new engineering approach to radiological imaging, could overcome the visual limit of the sonographer. Objectives This study is aimed at extracting objective testicular US features, correlating with testicular function, including both spermato- and steroidogenesis, using engineering approach, in order to overcome the operator-dependent subjectivity. Materials and methods Prospective observational pilot study from December 2019 to December 2020 on normozoospermic subjects and patients with semen variables alterations, excluding azoospermia. All patients underwent conventional semen analysis, pituitary-gonadal hormones assessment and testicular US, performed by the same operator. US images were analysed by Biolab (Turin) throughout image segmentation, image pre-processing and texture features extraction. Results 170 US testicular images were collected from 85 patients (age 38.6±9.1 years). A total of 44 first-order and advanced features were extracted. US inhomogeneity defined by radiomics significantly correlate with the andrologist definition, showing for the first time a mathematical quantification of a subjective US evaluation. 13 US texture features correlated with semen parameters, predicting sperm concentration, total sperm number, progressive motility, total motility and morphology, and with gonadotropins serum levels, but not with total testosterone serum levels. Classification analyses confirmed that US textural features predicted patients' classification according to semen parameters alterations. Conclusions Radiomics texture features qualitatively describe the testicular parenchyma with objective and reliable quantitative parameters, reflecting both the testicular spermatogenic capability and the action of pituitary gonadotropins. This is an innovative model in which US texture features represent a mirror of the pituitary-gonadal homeostasis in terms of reproductive function. This article is protected by copyright. All rights reserved.

Pituitary gonadotropins play an essential and pivotal role in the control of human and animal reproduction within the hypothalamic-pituitary-gonadal (HPG) axis. The computational modeling of pituitary gonadotropin signaling encompasses phenomena of different natures such as the dynamic encoding of gonadotropin secretion, and the intracellular cascades triggered by gonadotropin binding to their cognate receptors, resulting in a variety of biological outcomes. We overview historical and ongoing issues in modeling and data analysis related to gonadotropin secretion in the field of both physiology and neuro-endocrinology. We mention the different mathematical formalisms involved, their interest and limits. We discuss open statistical questions in signal analysis associated with key endocrine issues. We also review recent advances in the modeling of the intracellular pathways activated by gonadotropins, which yields promising development for innovative approaches in drug discovery. The greatest challenge to be tackled in computational modeling of pituitary gonadotropin signaling is the embedding of gonadotropin signaling within its natural multi-scale environment, from the single cell level, to the organic and whole HPG level. The development of modeling approaches of G protein-coupled receptor signaling, together with multicellular systems biology may lead to unexampled mechanistic understanding with critical expected fallouts in the therapeutic management of reproduction., Comment: in press

To determine the prevalence of hypogonadotropic hypogonadism (HH) among patients with non-functioning pituitary adenomas (NFPA) and the post-surgery outcome on pituitary gonadotropins secretion (PGS); to determine the prevalence of erectile dysfunction (ED) on male patients with NFPA, to evaluate the impact of testosterone replacement therapy (TRT) in those with HH. Retrospective evaluation of gonadal function in 109 NFPA patients (45 males), with a mean age of 51.8 years, diagnosed on the last 10 years. ED questionnaire applied to 34 male patients. Male patients with NFPA were significantly older (males 58.1±15.8 vs. females 47.4±16.94; p=0.001). Most patients had macroadenomas (67%; p=0.001) and only a minority were incidentalomas (19%; p NFPA was more frequent in older rather than younger patients. Males were older, had more HH and surgery. There was no significant improvement of pituitary function with surgery (17%) and 13% became iatrogenic HH. TRT had a low efficacy to improve ED in these patients.

The aim of the study is to investigate the changes of serum leptin and kisspeptin levels in children and adolescents with different pubertal stages and nutritional states. A total of 647 Chinese children and adolescents were recruited, and serum estradiol, testosterone, pituitary gonadotropins, leptin, and kisspeptin levels were measured. The results showed that serum leptin levels of boys in T2 stage were the highest among the five stages, while they showed a gradual increase from T1 to T5 stage in girls and reached the highest in T5 stage (P<0.05). Conversely, serum kisspeptin levels of boys were higher in T4 and T5 stages than those in T1 stage, while its levels of girls were the highest in T2 stage, 21.4% higher than those in T1 stage (P<0.05). Both leptin and kisspeptin levels were positively correlated with BMI, WC, and weight in all boys and girls (all P<0.05). In conclusion, kisspeptin levels were firstly found to be notably changed in pubertal stages and nutritional status in Chinese children and adolescents with a significant sexual dimorphism. Obese/overweight girls had higher kisspeptin levels, and there was a positive correlation between kisspeptin and FSH and LH and obesity-related parameters in all boys and girls.

Reproduction is regulated by the hypothalamic-pituitary-gonadal (HPG) axis in vertebrates. In addition to wealth of knowledge in mammals, recent studies in non-mammalian species, especially teleosts, have provided evidence that some of the components in the HPG axis are conserved in bony vertebrates. On the other hand, from the comparisons of the recent accumulating knowledge between mammals and teleosts, unique characteristics of the regulatory system in each group have been unveiled. A hypophysiotropic neurotransmitter/hormone, gonadotropin releasing hormone (GnRH), pituitary gonadotropins, follicle stimulating hormone (FSH), and luteinizing hormone (LH) were proven to be common important elements of the HPG axis in teleosts and mammals, although the roles of each vary. Conversely, there are some modulators of GnRH or gonadotropins that are not common to all vertebrates. In this review, I will introduce the mechanism for HPG axis regulation in mammals and teleosts, and describe their evolution from a hypothetical common ancestor.

El uso de los tallos intrauterinos de oro, plata o acrílicos constituye hoy día un procedimiento inocuo. Su uso está especialmente indicado en la dismenorrea espasmódica de causa uterina, en las atresias e hipoplasias uterinas, estenosis del cuello, en las hiperanteflexiones uterinas y en las esterilidad condicionada por ciertos factores cervicales o de causa criptogenética. Se insiste en las ventajas de usar un modelo original del autor que ha sido ideado especialmente para corregir la esterilidad. Los tallos hechos de goma (caucho) deben proscribirse. Se presentan los resultados obtenidos en 40 casos en que se logró curar la esterilidad en el 30% de 22 pacientes estériles, la dismenorrea en el 71% de entre 9 pacientes y las atresias cervicales o corporales en el 88% de otras 9 enfermas. En la mitad de las pacientes se comprobó un crecimiento discreto e indoloro de uno de los ovarios lo que se atribuye a una descarga de gonadotrofinas hipofisiarias provocada por un reflejo partido del cuello uterino.

This study aimed to investigate the effect of zinc supplementation on testicular tissue as a feed-back mechanism of the pituitary secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on cigarette smoker subjects. Total of twenty subjects participated in this study as per the national bioethics committee guidelines. Venous blood samples were collected for determination of serum level of LH and FSH before and after zinc supplementation. LH and FSH determination were done using enzyme-linked immunosorbent assay (ELISA). A t-test was used to compare the means of two groups, P value was considered significant if ≤ 0.05. Results showed that LH serum levels were elevated in smokers as compared to the control group (p 0.05). Similar observation was found in FSH levels (p>0.05). After one month of zinc supplementation, LH levels decreased in smokers group (after: 4.14 ± 2.38 mlU/ml, before: 7.43 ± 4.32 mlU/ml; p>0.05). FSH levels also decreased after zinc supplementation in smokers group (after: 1.50 ± 1.12 mlU/ml, before: 3.88 ± 1.57 mlU/ml; p>0.05). The improving effect of zinc supplementation on LH and FSH pituitary and testicular steroid secretions for smoker subjects is obviously observed. These findings can be implemented to contribute to the outcome of zinc treatment associated with smoking. Key words: Zinc, biometals, smoking, gonadotropins, luteinizing hormone (LH), follicle-stimulating hormone (FSH), trace elements.

Gonadotropins play fundamental roles in reproduction. More than 30years ago, Cga transgenic mice were generated, and more than 20years ago, the phenotypes of Cga null mice were reported. Since then, numerous mouse strains have been generated and characterized to address several questions in reproductive biology involving gonadotropin synthesis, secretion, and action. More recently, extragonadal expression, and in some cases, functions of gonadotropins in nongonadal tissues have been identified. Several genomic and proteomic approaches including novel mouse genome editing tools are available now. It is anticipated that these and other emerging technologies will be useful to build an integrated network of gonadotropin signaling pathways in various tissues. Undoubtedly, research on gonadotropins will continue to provide new knowledge and allow us transcend from benchside to the bedside.

The kinetic of changes in plasma concentrations and pituitary contents of FSH, LH, prolactin after hysterectomy and treatment with steroid-free uterine extracts were studied in adult, non-pregnant female rats. The post-castration rise of plasma and pituitary FSH and plasma LH was inhibited but the plasma prolactin was elevated by hysterectomy. Steroid-free uterine extracts from previously castrated animals increased the plasma FSH, LH and prolactin concentrations in hysterectomized females 48 hours after administration. Uterine extracts from intact and oestradiol-substituted-castrated animals decreased the pituitary prolactin content 48 h after single i.p. injection. Pituitary FSH and LH contents were not affected by single dose of uterine extracts at any time which were examined. It is concluded that the uterus may play some role in the synthesis and release of pituitary gonadotropins and prolactin.

The aim of the study was to evaluate the ability of a novel web and mobile application to identify a woman's ovulation day and fertile window, in order to use it as a method of natural birth control.A retrospective study was performed on 1501 cycles of 317 women aged 18 to 39 years. Women entered their basal body temperatures, ovulation test results and date of menstruation into the application.The mean delay from the first positive ovulation test to the temperature-based estimation of the ovulation day was 1.9 days; the length of the luteal phase varied on average by 1.25 days per user. Only 0.05% of non-fertile days were falsely attributed and found within the fertile window.The method is effective at identifying a user's ovulation day and fertile window and can therefore be used as a natural method of birth control.

In a 1953 editorial entitled “The Need for an Inhibitor of Gonadotropin,” Lawson Wilkins noted that a “method of suppressing the secretion of pituitary gonadotropins . . . might lead to the prevention or control of sexual precocity.”1 Almost 30 years later, Crowley and colleagues reported successful suppression of early puberty in a two-year-old girl with the use of a long-acting analogue of a luteinizing hormone–releasing hormone (LHRH) agonist.2 In the intervening years, the nature of the hypothalamic–pituitary–gonadal axis was elucidated, LHRH was isolated, and maturational changes in the reproductive axis were characterized (Figure 1). Before puberty, the LHRH neurons . . .

The search for effective antifertility vaccines has been actively pursued for decades in clinical applications as contraceptives or in the treatment of hormone-dependent conditions. More recently, innovations have seen immunocontraception being employed successfully in veterinary and farming applications, as well as in population control of a number of different wildlife species. Although the basic principle behind these vaccines is the same, design considerations and criteria for commercialization are very different. This review will examine current advances in this field and evaluate the future scope of antifertility vaccines.

In this study, an attempt was made to induce ovulation in crossbred pre-pubertal heifers by the use of clomiphene citrate (an anti-estrogen) and hCG. The hypothesis was that the clomiphene citrate, being anti-estrogen, would remove negative feedback effect of estrogen on the release of pituitary gonadotropins. Elevated gonadotropins would support ovarian follicular growth to a point where hCG would induce ovulation. Six pre-pubertal heifers were given clomiphene citrate orally at 300 mg/heifer for 9 days. At the same time, six control heifers were given placebo tablets. On following day, hCG was given to all heifers at a dose of 2500IU. Blood was collected before, during and after treatment and plasma was assayed for progesterone (P4) and estradiol (E2) concentrations. Five heifers (83.3%) in the experimental group had E2 concentrations above 10 pg/ml compared to one heifer (16.7%) in control group. Due to a wide variation, mean E2 concentration did not differ significantly between experimental and control heifers. The P4 assays showed that four heifers (66.7%) in the experimental group had ovulated (P41ng/ml plasma) compared to one heifer (16.7%) in control group, and mean P4 concentration differed (P0.05) when concentrations were greatest in the clomiphene citrate-treated heifers. In conclusion, clomiphene citrate along with hCG can be used to induce ovulation in pre-pubertal heifers.

Ovulation induction using clomiphene citrate, gonadotropins, and gonadotropin-releasing hormone is reviewed. The short- and long-term consequences of these therapies are discussed in detail.

Resume Le syndrome d'interruption de la tige pituitaire represente une cause de deficit en hormone de croissance de frequence non negligeable. Population et methodes. Nous avons etudie 22 enfants (13 garcons, neuf filles) âges, lors des premieres manifestations cliniques, de 2 jours a 10 ans (moyenne: 5,33 ± 2 ans). Le diagnostic de syndrome d'interruption de la tige pituitaire a ete porte sur les donnees de PIRM. La recherche des antecedents a permis de mettre en evidence une souffrance foetale dans 12 cas (54,5%), un traumatisme crânien dans trois cas (13%), une anomalie de la ligne mediane dans trois cas (13%). Les premieres manifestations on ete une hypoglycemie neonatale (deux cas), un ralentissement de la vitesse de croissance (18 cas), un diabete insipide (deux cas). Resultats. Le deficit en hormone de croissance etait complet et inaugural dans 19 cas sur 22, et isole dans quatre cas. Les deficits en ACTH et TSH etaient presents dans 15 cas sur 22. Le diabete insipide etait present dans six cas et revelateur dans deux cas. Chez tous les enfants qui avaient depasse l'âge normal de la puberte ( n = 10), il existait un deficit gonadotrope. Dans notre serie, l'intervalle libre est tres variable et ne depend pas de la cause. Conclusion. Le syndrome d'interruption de la tige pituitaire, de connaissance recente, est de frequence non negligeable; il est important de le rechercher dans les suires d'un traumatisme crânien ou d'une souffrance fœtale. Le risque est l'evolution progressive vers un panhypopituitarisme, qu'il faut rechercher regulierement.

The aim of this study was to compare the responses of pituitary gonadotropins and the free α-subunit (FAS), measured by sensitive immunofluorometric assays at 0, 30 and 60 min after 100 µg GnRH i.v. in a group of 32 normal prepubertal boys (NB) and a group of 17 adult males with complete hypogonadotropic hypogonadism (HH). At time 0 min, medians of the serum levels of LH, FSH and FAS were not different in both groups. At 30 min (29.81 and 8.56 pmol/l) and 60 min (24.10 and 7.74 pmol/l) as well as peak levels (29.76 and 8.56 pmol/l), ‘deltas’ (peak minus baseline; 25.89 and 0.34 pmol/l) and ‘fold’-increase (peak divided by baseline; 7.0-fold and 1.6-fold), the medians were significantly higher in NB than in HH, respectively. There were fewer overlapping values of FAS between the 2 groups and they occurred in only 4% of the total number of subjects when ‘fold’ was considered. The measurement of FAS by a very sensitive immunofluorometric assay, after GnRH, distinguishes responses of NB from those of adult men with HH, that is of functional from permanent HH.

The endocannabinoid system (ECS) has a well-documented pivotal role in the control of mammalian reproductive functions, by acting at multiple levels, that is, central (CNS) and local (gonads) levels. Since studies performed in animal models other than mammals might provide further insight into the biology of these signalling molecules, in the present paper we review the comparative data pointing toward the endocannabinoid involvement in the reproductive control of non-mammalian vertebrates, focussing in particular on the central regulation of teleost and amphibian reproduction. The morphofunctional distribution of brain cannabinoid receptors will be discussed in relation to other crucial signalling molecules involved in the control of reproductive functions, such as GnRH, dopamine, aromatase, and pituitary gonadotropins.

The immune system and several endocrine axes communicate with each other through a network of molecules which collectively produce a coordinated response to immune challenges. This phenomenon, necessary for the survival of the organism, is thought to involve the release, by activated cells in the periphery, of proteins, called cytokines, which inform the brain about immune activation. The brain then organizes a series of neuroendocrine responses which participate in the regulation of the host response. With regard to the influence of cytokines on the hypothalamic-pituitary-gonadal axis, we know that the injection of these proteins lowers gonadotropin-releasing hormone release, which in turn inhibits luteinizing hormone (LH) secretion. These changes would be expected to decrease sex steroid production and, indeed, estrogens and testosterone are low in female and male rats, respectively, following acute intracerebroventricular (i.c.v.) injection of interleukin (IL)-1 beta. There is, however, another possibility that central cytokines could alter ovarian and testicular function independently of changes in gonadotropin levels. Prolonged i.c.v. infusion of the cytokine into the female rat brain produced a dramatic rise in progesterone levels. The absence of a comparable change in the progesterone release rate of males infused with IL-1 beta, and the presence of marked surges of prolactin (PRL) in the females, suggests that IL-1 beta altered ovarian function, and that the persistence of large corpora lutea induced PRL release. The possibility that the cytokine might stimulate the brain circuits that regulate PRL release, while possible, appears remote, because male rats injected with IL-1 beta showed significantly blunted PRL levels. In intact adult male rats, i.c.v. IL-1 beta administration caused the expected decrease in LH and testosterone levels, but was also accompanied by a loss of testicular responsiveness to gonadotropins. Though elevated levels of corticosteroids are known to interfere with normal gonadal steroidogenesis, blockade of IL-1-induced corticosterone release did not reverse the inhibitory influence of the cytokine. One mechanism that deserves attention is the possibility that i.c.v. injection of IL-1 beta might increase circulating cytokine levels, and indeed plasma IL-6 concentrations were significantly elevated in rats treated with IL-1 beta. This humoral mechanism may disrupt testicular function through the documented inhibitory effects of blood-borne cytokines on Leydig cell function. In addition, brain cytokines might influence a variety of peripheral events through direct (neural?) connections. This brief review discusses the hypothesis that there are brain-to-gonad connections that bypass the pituitary, and presents results that might support the possibility that central injection of IL-1 beta decreases testosterone secretion independently of blunted LH levels.

The pituitary gonadotropins FSH and LH are secreted into blood as dimeric glycoproteins which display a wide heterogeneity when submitted to technique of separation based on electric charge. That supports the assumption of a major role of the carbohydrates moieties as a source of heterogeneity. No clear difference however has been demonstrated in the biological potency of the different isoforms occurring in blood. On the contrary, important discrepancies in immunological activity have been evidenced, mainly as far as LH is concerned. This is particularly important from a practical point of view since some monoclonal sandwich assays widely used for the measurement of LH levels fail to detect LH in samples from certain subjects. The description of the so-called “invisible LH” phenomenon should prompt international organizations to incite the manufacturers of commercial kits to improve the standardization in gonadotropin assays.

Controversial opinions exist about the possible mechanisms throughout emergency contraception prevents pregnancy. Recently, the International Federation of Gynaecology and Obstetrics and the International Consortium for Emergency Contraception released a Joint Statement declaring that ‘inhibition or delay of ovulation should be their primary and possibly only mechanism of action’. They still added that ‘Review of the evidence suggests that LNG-ECPs cannot prevent implantation’. Concerning levonorgestrel-only emergency contraceptive pills effects on ovulation, the Statement based on seven reference papers which considered a total of only 142 patients, divided into still different subgroups. Basing on their same references we got quite different conclusions.

Publisher Summary This chapter focuses specifically on the interactions between the hypothalamic–pituitary–interrenal (HPI) stress axis and the hypothalamic–pituitary–gonadal (HPG) reproductive axis and the consequences of these interactions for reproductive processes. It also examines that how stressors and the mediators of the stress response affect the key effectors of the HPG axis, including the hypothalamic gonadotropin–releasing hormones, the pituitary gonadotropins, the gonadal sex steroids, and hepatic vitellogeni. The chapter reviews how stressors and stress hormones impact the development of the reproductive system and reproductive functions at the embryonic, larval, pubertal, and adult life stages. The influence of stress on reproduction depends on the type of stressor, its intensity and duration, the sex of the fish, its developmental stage, its nutritional status, and its reproductive strategy. The effects of gender and reproduction on the activity of the HPI axis are discussed.

Immunohistochemical localization of pituitary gonadotropins (FSH, LH) and estrogen was investigated in 17 ovaries from ten postmenopausal women. Positive immunostaining for 17 beta-estradiol was demonstrated in the cortical stroma of 14 postmenopausal ovaries. Positive immunostaining for FSH was localized in the cortical stroma of 12 postmenopausal ovaries, and positive immunostaining for LH was also localized in 12 ovaries. Immunohistochemical localization for pituitary gonadotropins (FSH and/or LH) and 17 beta-estradiol was identified in the same hypertrophic cortical stroma of 13 postmenopausal ovaries. The ultrastructural study suggested steroidogenic activity in the cortical stromal cells of the postmenopausal ovary. In addition, peripheral and ovarian venous concentrations of 17 beta-estradiol were measured in 13 postmenopausal subjects, and significant concentration gradient for serum 17 beta-estradiol was noted. The ovarian/peripheral concentration gradient for 17 beta-estradiol had a tendency to be higher in the subjects with positive immunostaining for 17 beta-estradiol compared with that in the subjects with negative immunostaining. The present results suggest that the human ovary secretes estrogen in response to pituitary gonadotropins even after the menopause.

Although there is general agreement about the polycystic ovary as an anatomic entity, a classic description of an associated syndrome remains elusive. This lack of definition, however, has not impeded clinical investigation. This article focuses on the diagnosis, pathogenesis, hypotheses, and treatment of polycystic ovarian disease.

Hypothalamic control of the pituitary-gonadal axis in broad terms operates at two levels. The first level mediates longer-term responses to maturational signalling, to environmental and behavioural factors such as changes in photoperiod and availability of food, and to the expression of incubation behaviour. The second level of control mediates shorter-term reproductive responses. Dopamine is emerging as a potential key regulator at both levels of control, being stimulatory at the GnRH-I cell body and inhibitory at the median eminence. This article discusses the hypothalamic control; role of cGnRH-I in key events in the reproductive cycle; neurotransmitter and neuropeptide control of cGnRH-I; pituitary glands; avian GnRH receptors; avian GnRH receptor structure and function; follicle-stimulating hormone (FSH); luteinizing hormone (LH); gonadotrophe common alpha subunit; gonadotrophin inhibitory hormone (GnIH); other forms of GnRH; ovarian gonadotrophin receptors; and the genetics and hypothalamic-pituitary-gonadal axis in poultry.

The pituitary gonadotropins LH and FSH, like other glycoproteins, are not unique proteins but consist of related isoforms that can be separated on the basis of size, charge, biologic to immunologic potency relationships, and plasma clearance. In this article we briefly review the known biochemical structure, synthetic pathways, and gonadal target cell receptor function for both gonadotropins. The currently available data regarding gonadotropin bioactivity during development and puberty as well as evidence for differential regulation of LH and FSH are reviewed. At each stage of puberty the bioactive gonadotropin potencies and known isoform distribution are related to physiologic events and known changes in gonadal development.

Background and Aims: Retrospectivestudies have indicated that internationally adopted girls are at high risk of developing precocious puberty. Hypothetically, this could be due to selection bias. The aim of this study was to determine age at reaching pubertal milestones in healthy internationally adopted girls in a prospective, clinical study. Methods: A longitudinal cohort study including 276 randomly recruited internationally adopted girls. At baseline, age ranged from 4 to 13 years. Participants were followed with biannual examinations over a period of 2 years. Examinations included height, weight, Tanner staging, blood sampling and bone age assessment. Age distribution at entering pubertal stages B2–B5 (breast development), PH1–PH5 (pubic hair development) and menarche was estimated by probit analysis. Data were compared to a reference population of Danish-born girls, studied cross-sectionally. Results: Mean age at B2+ was 9.5 years (95% prediction interval 7.1–12.0 years) and mean age at menarche was 12.1 (10.2–14.0) years in adopted girls, which was significantly lower compared to the reference group (p < 0.0003). 16% of adopted girls entered stage B2 before 8 years of age. The puberty-related rise in LH, FSH and estradiol was detected at earlier ages in adopted girls compared to the reference group. Conclusion: Internationally adopted girls have a significantly higher risk of precocious pubertal maturation compared to Danish-born girls.

Background/Aims: The dose, frequency and contour of GnRH stimulation of the pituitary gonadotrope have been shown to be independent variables influencing pituitary LH secretion. The dynamic interaction between these variables during physiological and pathophysiological states has yet to be examined. Methods: Twelve men with GnRH deficiency and idiopathic hypogonadotropic hypogonadism undergoing GnRH therapy participated in a series of studies in which 2 log orders of GnRH doses (2.5–250 ng/kg) were administered at frequencies varying from 0.5 to 8 hourly. Pituitary responses were characterized by pulse amplitudes and nadirs. The relative sensitivity of the gonadotrope to GnRH was defined as that dose of GnRH capable of eliciting an LH pulse amplitude equal to the mean LH amplitude in normal men. Results: As GnRH stimulation of the gonadotrope slowed from 0.5 to 8 hourly, pulse amplitudes of LH increased whereas mean nadirs decreased (p < 0.05). Unique, curvilinear dose-response curves were found for each frequency that demonstrated an increasing slope (p < 0.03) as the frequency of GnRH stimulation slowed. Thus, the relative sensitivity of the gonadotrope increased as the frequency of GnRH stimulation decreased over the range of physiological frequencies tested. Conclusions: We conclude that a delicate interplay exists between the dose and frequency of GnRH stimulation of the gonadotrope that determines pituitary LH gonadotropin responsiveness in the human. Slower frequencies favor increased LH release largely due to decreasing LH nadirs and improved sensitivity of the gonadotropes to GnRH stimulation.

Publisher Summary This chapter summarizes evidence that aging effects at all three levels of the hypothalamic-pituitaryovarian (HPO) axis may contribute to the progressively pronounced hypersecretion of pituitary gonadotropins that occurs at the close of the reproductive years. Best understood of the contributors to the aging-related alterations in gonadotropin-releasing hormone (GnRH) secretion are the ovarian causes. There is heightened interest in the role of central aging deficits in the etiology of the menopause. A fundamental question is whether GnRH secretion increases at the time of menopause, and if so, whether this is mediated by declines in the integrity of central circadian pacemakers. This hypothesis provides important new directions for studies of the HPO axis at menopause. An understanding of the factors that interact and initiate the process of hypoestrogenism in aging women is needed to develop strategies for alleviating the negative aspects of the menopause and to better comprehend the process of biologic aging.

As modificações nas concentrações das gonadotrofinas ao longo da vida reprodutiva dependem de amadurecimento funcional harmônico entre conexões neurais, neurônios-GnRH no hipotálamo, gonadotropos hipofisários e células da granulosa e teca da parede folicular. As concentrações de LH e FSH sofrem variações com o período do dia, fase do ciclo menstrual e idades ginecológica e cronológica. A variação circadiana é marcante para o LH e ocorre na fase puberal, quando os pulsos têm maior freqüência e amplitude no período noturno. Na fase puberal tardia, os pulsos das gonadotrofinas ocorrem também durante o dia e perdem a variação noite-dia, permanecendo discretas alterações durante as 24 horas do dia. No ciclo menstrual, durante os anos reprodutivos, o FSH eleva-se no final da fase lútea tardia, declina na fase folicular média, eleva-se bruscamente na fase ovulatória e permanece em níveis basais até a fase lútea tardia. O LH permanece em níveis constantes durante toda a fase folicular, eleva-se no pico ovulatório e declina a níveis basais na fase lútea. Na quarta década, há modificações hipotálamo-neurais na secreção de GnRH, atenuação do retrocontrole positivo exercido pelo estradiol e diminuição na freqüência e prolongamento dos pulsos de GnRH. A hipófise responde com diminuição na densidade de receptores-GnRH, perda da sensibilidade do gonadotropo, secreção de gonadotrofinas mais básicas com maior meia-vida, diminuição na freqüência e maior amplitude dos pulsos de LH e FSH e secreção preferencial de FSH. Estas modificações, associadas à aceleração no consumo folicular, explicam a elevação monotrópica mais rápida de FSH após os 37-38 anos e a manutenção de níveis quase constantes de LH até o final do período reprodutivo. Estudos consistentes mostram que a elevação seletiva dos níveis basais de FSH na fase folicular precoce na verdade é gradual, sendo observada já na terceira década de vida. A discordância entre pulsos e níveis basais de FSH e LH ao longo dos anos reprodutivos permite especular a existência de mecanismos mais complexos, não totalmente compreendidos, na regulação do eixo hipotálamo-hipófise-ovariano.

There is a need to develop new contraceptives, particularly for men whose current choices are suboptimal in terms of effectiveness and ease of reversibility. Recent surveys indicate that men and their partners would be willing to rely on male hormonal contraceptives. Male hormonal contraception works by reversibly suppressing sperm production. Testosterone in combination with progestins or gonadotropin-releasing hormone antagonists induces profound and consistent sperm suppression. Asian men are more susceptible to the suppressive effects of testosterone given alone, even if they may benefit from the addition of an adjunctive agent to obtain optimal contraceptive protection. The aim of this review is to comment on the recent relevant achievements in the field.

In this article we examine the issue of early puberty in girls. First, a brief overview of normal pubertal development is provided, including the two endocrine components of puberty: gonadarche and adrenarche. Second, we critically discuss the controversy regarding whether puberty truly is occurring earlier in girls. Third, we emphasize one type of early puberty, the case of premature adrenarche (PA). PA is used to illustrate the importance of identifying types of early puberty, evaluating the types to determine causality, determining whether follow-up of early puberty is necessary, and showing the potential ramifications of ignoring this variation in pubertal development. Findings from a pilot study comparing PA and on-time puberty children are used to show the importance of determining whether early puberty is normal in all cases.

Central precocious puberty refers to the activation of gonadal hormone secretion that is mediated by the pituitary gonadotropins follicle-stimulating hormone and luteinizing hormone and occurs at an age traditionally defined as less than 9 years in boys.

Objective To report on a patient with thalidomide-induced amenorrhea and review the literature on the effect of thalidomide on ovarian function. Design Case report and literature review. Setting University medical center. Patient(s) A twenty-eight-year-old woman referred for a 2-year history of amenorrhea. Intervention(s) History, physical examination, laboratory evaluation of the patient, and subsequent medical therapy. Literature review performed by using OVID/Medline and PubMed search strategies. Main outcome measure(s) Diagnosis and appropriate management of thalidomide-induced amenorrhea. Result(s) Elevated pituitary gonadotropins, other labs normal. All known causes of hypergonadotropic amenorrhea were excluded. Conclusion(s) Thalidomide induces hypergonadotropic amenorrhea. Although this effect appears to be reversible, the long-term effect of thalidomide on ovarian reserve is unclear.

Exogenously administered testosterone suppresses the release of pituitary gonadotropins and, hence, spermatogenesis, and it is central to efforts to create a hormonal contraceptive for men. When given alone, however, currently used forms of testosterone are not completely effective at reducing sperm counts to zero in all men. Therefore, newer androgens and agents such as progestins and gonadotropin-releasing hormone (GnRH) analogs that synergistically suppress gonadotropin release are being studied in efforts to develop a safe, effective, and commercially viable hormonal contraceptive for men.

We determined the complete amino acid sequences of two pituitary gonadotropins, follitropin and lutropin in the ostrich, thereby providing the first information on the structure of avian follitropin. Ostrich follitropin and lutropin both consist of two subunits: a common alpha-subunit and a hormone-specific beta-subunit. The alpha-subunit is composed of 96 amino acid residues and has 70-80% sequence identity with the alpha-subunits of most vertebrates. The ostrich follitropin beta-subunit consists of 106 amino-acid residues, and shows 70-74% sequence identity with mammalian follitropins beta, 61% with amphibian follitropin beta, 39-46% with teleost gonadotropins II beta and 32-44% with teleost gonadotropins I beta. The ostrich lutropin beta-subunit consists of 128 amino-acid residues, and exhibits 76-78% sequence identity with other avian lutropins beta, 44-50% with teleost gonadotropins II beta, 45% with amphibian lutropin beta, 41-44% with mammalian lutropins beta, and 25-36% with teleost gonadotropins I beta. Sequence comparison revealed that lutropin beta-subunits are more class-specific and have diversified approximately twice as fast follitropin beta-subunits, although segments essential for maintaining higher-order structures have been conserved.

The ovarian response to the stimulatory actions of pituitary gonadotropins is modulated by the local production and action of local factors. Current advances in biochemical and molecular research techniques have facilitated the progress in our understanding of how prostaglandins (PGs) are inherently involved in the physiological events influencing ovarian cellular function in all mammalian species, particularly during ovulation and luteolysis. The purpose of this review is to incorporate recent findings with previous data, highlighting the novel characterization of the PG F2 alpha receptor and other PG receptors, and their intracellular signaling mechanisms in relation to ovarian function.

Publisher Summary This chapter discusses the current status of the investigations on the hormonal regulation of oocyte growth and maturation in fish. Pituitary gonadotropins are of primary importance in triggering these processes in fish oocytes. In both cases, however, the actions of gonadotropins are not direct but are mediated by the follicular production of steroidal mediators, estradiol-17β (oocyte growth), and 17α,20β-dihydroxy-4-pregnene-3-one (DP) or 4-pregnen-17,20β,21-triol-3-one (20β-S) (oocyte maturation). It has been established that both estradiol- 17β and 17α,20β-DP are biosynthesized by salmonid ovarian follicles through an interaction of two cell layers—namely, the thecal and the granulosa cell layers (two-cell-type model). The granulosa cell layers are the sites of production of these two steroidal mediators, but their production depends on the provision of the precursor steroids by the thecal cell layers.