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Parathyroid hormone (PTH) secretion from abnormal hyperfunctioning human parathyroid tissues was studied in vitro to determine whether abnormal tissues were responsive to changes in calcium concentration and what role their subcellular organelles played in secretion. Hyperfunctioning tissues from one patient with secondary parathyroid hyperplasia, four patients with parathyroid adenomas, and one patient with parathyroid carcinoma were incubated in media containing low calcium (0.75 mM), normal calcium (1.5 mM), high calcium (3.0 mM), or vinblastine (0.01 mM), a microtubular disrupter. Also, in order to correlate ultrastructural responses with PTH secretion, after incubation tissues of one adenoma were objectively quantitated by stereologic techniques. Low calcium consistently stimulated mean PTH secretion from hyperplastic and adenomatous tissue, but only during the 1st hour of secretion. Low calcium inconsistently stimulated carcinomatous tissue. High calcium suppressed mean PTH release from all tissues. Vinblastine did not consistently inhibit secretion from adenomatous or hyperplastic tissue. Ultrastructural analysis of adenomatous tissue showed a sparsity of granules (0.87 per cent of cellular volume) compared to previously studied bovine tissues. Low calcium significantly increased the volume fraction of pinocytotic vesicles to 300 per cent (p less than 0.01) and reduced the surface area of straight (inactive) membrane to 60 per cent (p less than 0.01) of the normal calcium control. Secretion granules, when present, were adjacent to submembrane vesicles. The number and structure of microtubules were not changed by low or high calcium or vinblastine. Our findings indicate that parathyroid adenomas and hyperplastic tissues can respond acutely to low calcium stimulation and high calcium suppression. However, the acute response to low calcium stimulation may not be sustained in some cases because of limited storage of hormone. The increase in pinocytosis in low calcium-stimulated tissue suggests a coupling of exocytosis with membrane endocytosis, possibly related to membrane recycling. Our findings with vinblastine suggest that microtubular integrity is not a prerequisite for basal PTH secretion in adenomatous tissue.

This study was undertaken to evaluate the physiological role, if any, of dopamine (DA) in modulating parathyroid hormone (PTH) and calcitonin (CT) secretion in man. Infusion of DA (5 micrograms/kg/min) into 6 normal men, decreased serum immunoreactive prolactin (iPRL) and concomitantly increased serum iPTH to 140 +/- 6.8% of baseline (P less than 0.01) at 30 min, with decline thereafter, despite continuation of the DA infusion. Serum iCT levels did not significantly change. Chlorpromazine (50 mg IM), decreased serum iPTH to 75 +/- 5.4% and 79 +/- 3.7% of baseline (P less than 0.01) at 30 and 60 min, respectively, associated with an increase in iPRL. There was subsequent return of iPTH to baseline even though iPRL remained elevated. iCT levels did not significantly change. These observations would suggest that DA may play a physiological role in iPTH, but not iCT, secretion. However, infusion of more nearly physiological doses of DA (0.02, 0.2, and 2.0 micrograms/kg/min) lowered serum iPRL to levels similar to those after the larger DA dose, but with no concomitant increase in either iPTH or iCT. Also, 1) the DA agonist bromocriptine decreased serum iPRL without modifying iPTH or iCT; 2) the DA precursor, levodopa, and the DA antagonist, metoclopramide, had no effect on serum iPTH or iCT levels. These studies suggest that 1) the transient stimulatory effect of DA on iPTH secretion is pharmacological, and 2) DA does not have a physiological role in secretion of iPTH or iCT in man.

Administration of aminophylline to intact rats did not cause a change in serum Ca, but did cause a significant increase in serum PTH. Administration of EDTA alone caused hypocalcemia, and a greater increase in PTH than that caused by aminophylline alone. Aminophylline plus EDTA given togeather caused no greater hypocalcemia, but a significantly greater increase in PTH than that by EDTA alone. Therefore, aminophylline increased PTH secretion when given alone, and also enhanced the PTH secretion stimulated by EDTA-induced hypocalcemia in vivo.

The effect and the mechanism of insulin-induced hypoglycemic stress on parathyroid hormone (PTH) secretion in man was evaluated. Porcine crystalline insulin (0.1 U/kg,iv) caused symtomatic hypoglycemia in all subjects. The maximum hypoglycemia occurred between 25 and 35 min following the insulin administration. A significant increase in the serum PTH concentration occurred promptly at 5 min following the time of maximum hypoglycemia, achieving peak levels between 5 and 15 min. Thereafter the serum PTH concentration gradually declined, reaching baseline values of 60 min. Serum cortisol levels were increased, but not until 30 min following the maximum hypoglycemia, and remained significantly elevated at 60 min. Therefore the stimulation of PTH secretion was not caused by elevated levels of serum cortisol. The serum calcium and magnesium levels remained unchanged throughout the procedure. A significant and sustained decline in the serum inorganic phosphate levels occurred following insulin administration. The results indicate that hypoglycemic stress stimulates PTH secretion, presumably via increased epinephrine levels, and further suggest that adrenergic stimuli play an important role in the physiology of PTH secretion.

Maternal and fetal parathyroidd hormone (PTH) responsiveness to hypocalcemia induced by EDTA infusion (50 mg/kg over 2 h) was studied in rhesus monkeys in late pregnancy. Although baseline serum total calcium (Ca) levels in the fetus exceeded those in the mother (4.83 +/- 0.13 vs. 4.28 +/- 0.15 meq/liter; P < 0.001), PTH values were not significantly different (5.62 +/- 0.37 vs. 6.18 +/- 0.33 muleq/ml; P > 0.05). EDTA infusion directly to five fetuses produced significant hypocalcemia (maximal decline averaging 19 +/- 2%) and PTH response (maximal increase averaging 46 +/- 5%). In contrast, in four control studies involving fetal saline infusion, there were no significant changes in fetal Ca or PTH levels. Four maternal control infusions produced no significant changes in either Ca or PTH levels. A comparison of maternal and fetal PTH responses indicated considerable similarity, although fetal PTH levels tended to return to baseline somewhat more gradually after cessation of the hypocalcemic stimulus than did maternal levels. These studies indicate that fetal PTH secretion, both baseline and in response to hypocalcemia, is quantitatively similar to that of the adult, and thus, the fetal parathyroid does not appear to be suppressed by the relative hypercalcemia of late fetal life.

Previous studies have suggested a role for adrenergic stimuli in the regulation of PTH secretion. In the present studies, we evaluated the effect of endogenous catecholamine stimulation (by treadmill exercise) on serum calcium (Ca) and immunoreactive PTH (iPTH) in six healthy volunteers. Blood was collected for serum total Ca, ionized Ca, iPTH, cAMP, epinephrine, and norepinephrine before, during, and after exercise. As expected, plasma cAMP and catecholamine levels increased significantly during the exercise. In addition, there was an increase in serum total and plasma ionized Ca. However, serum iPTH levels did not change significantly at any of the times tested during and after exercise. The lack of change in serum PTH despite an increase in plasma catecholamines may be explained by 1) an increase in plasma ionized Ca by a separate mechanism (such as metabolic acidosis), which blocked an increase in serum iPTH, or 2) insufficient increase in plasma catecholamines to stimulate PTH secretion.

The possibility of parathyroid dysfunction as a causal factor in the osteopetrosis of the tl rats was explored by evaluating serum calcium (Ca) and immunoreactive parathyroid hormone (iPTH) concentrations in this strain of rats, as compared with those of phenotypically normal littermate (LM) and non-littermate (NLM) control groups. The mean serum Ca concentration in the tl rat was not significantly different from that of the NLM group, although it was less than that of the LM group. However, all Ca values were within the normal range. The mean serum iPTH concentration in the tl rats was not significantly different from those of either control group. The data indicate that the adult tl rat has adequate but not excessive PTH secretion. Therefore, osteopetrosis and its manifestations in the adult tl are not caused by an abnormality of parathyroid function.

In the rat, EDTA and isoproterenol stimulated PTH secretion, whereas high calcium and propranolol inhibited it. The stimulatory effects of EDTA and isoproterenol were still evident and unaltered in the presence of blocks induced by propranolol and high calcium, respectively. The findings suggest that: (i) both calcium and beta-adrenergic stimuli affect PTH secretion; and (ii) the two influences affect the PTH secretion by separate initial pathways.

Calcium metabolism during the menstrual cycle was studied in seven women from whom fasting blood samples were drawn daily or every other day throughout ovulatory cycles. Total calcium (Ca), ionic calcium (Ca++), magnesium (Mg), phosphorus (P), and immunoreactive parathyroid hormone (PTH) and calcitonin (CT) were measured. LH levels were used to date each cycle and progesterone levels were used to confirm ovulation. Plasma estradiol was measured in two of the subjects. In six subjects with cycle lengths of 27-31 days, PTH levels rose progressively through the follicular phase to a peak at or slightly before the LH surge, then fell progressively through the luteal phase; peak PTH levels were 30-35% above early follicular and late luteal values. CT levels were also highest at midcycle, but the CT pattern was somewhat more variable than that of PTH. Ca++ tended to fall until 3-4 days before ovulation and then to increase, while Ca, Mg, and P exhibited no particular pattern. One subject experienced a prolonged (44 day) ovulatory cycle characterized by three distinct PTH peaks, each of which coincided with elevations in plasma estradiol level. These results represent the first report of menstrual cyclicity in calcium-regulating hormones. The timing suggest an estrogen effect and it is hypothesized that estrogen inhibits PTH-induced bone resorption, lowering serum Ca++, which in turn provokes a compensatory PTH output. With the decline of the preovulatory estrogen peak, Ca++ levels rise and PTH secretion falls. Alternatively, it is possible that the primary action may be an estrogen-induced rise in CT release, causing hypocalcemia and consequent PTH output. Cyclic changes in PRL release or vitamin D metabolism might also be involved.

The effect of secretin on secretion of parathyroid hormone (PTH) and calcitonin (CT) was evaluated by both in vitro and in vivo techniques. In in vitro studies with bovine parathyroid tissue, Secretin-Boots caused significant dose-related increases in PTH secretion. In in vitro studies with rat thyroparathyroid tissue, Secretin-Boots caused significant increases in both PTH and CT secretion. Infusion of Secretin-Boots or of synthetic secretin in biologically equivalent doses into rats caused similar increases in secretion of PTH and of CT. Infusion of multiple doses of synthetic secretin revealed a dose-related stimulation of both PTH and CT secretion. Infusion of Secretin-Boots into normal human subjects caused prompt and progressive significant increases in secretion of both PTH and CT, with return to baseline values within 90 min after termination of the infusion. These data suggest that secretin can stimulate hormonal secretion by parathyroid and thyroid C cells and that secretin may play a modulating role in the secretion of both PTH and CT.

Purified secretin infused in an estimated physiological dose caused an increase in serum immunoreactive PTH (iPTH) and calcitonin (iCT) in man. Ingestion of a gastric acid-stimulating test meal, a procedure known to increase endogenous secretin, caused increases in serum iPTH and plasma iCT in normal subjects. Ingestion of antacid with the test meal blunted the increase in both iPTH and iCT. Ingestion of the test meal by pernicious anemia patients with achlorhydria caused no stimulation of either serum iPTH or plasma iCT. Therefore, based on the observations that 1) exogenous secretin stimulated iPTH and iCT, 2) an acid-stimulating test meal is known to stimulate endogenous secretin release (4), 3) the test meal increased both serum iPTH and iCT in normal man, an effect nullified by simultaneous antacid ingestion, and 4) the test meal caused no increase in either iPTH or iCT in achlorhydric patients, we conclude that endogenous secretin possibly mediates this effect of test meal and, therefore, may play a physiological role in modulating the secretion of PTH and CT.

Effects of somatostatin on basal and low calcium-, isoproterenol- or dibutryl cyclic AMP (DBcAMP)-stimulated parathyroid hormone (PTH) secretion were evaluated in vitro with bovine parathyroid tissue. Low calcium, isoproterenol or DBcAMP alone significantly stimulated PTH secretion. Somatostatin 1 or 4 microgram/ml significantly inhibited these stimulated PTH secretions. Inhibition of isoproterenol-stimulated PTH secretion was more complete than was the inhibition of low calcium- or DBcAMP-stimulated secretion. The studies indicate that somatostatin inhibits PTH secretion by an action distal to cAMP generation. The more complete inhibition of isoproterenol-stimulated PTH secretion suggests that somatostatin may also have additional effects on or proximal to the formation of cyclic AMP.

This study evaluated the effect of parasympathetic agonists and antagonists on immunoreactive (i) PTH secretion in vitro and on serum iPTH in vivo in rats. In in vitro studies pilocarpine or bethanechol significantly inhibited PTH secretion. This inhibition was blocked by the simultaneous addition of atropine to the incubation medium. In in vivo studies, the cholinergic agonists pilocarpine and bethanechol and the cholinergic antagonist atropine were administered to rats by IV infusion. Blood was obtained before and again after two hours of infusion for analysis of iPTH. Pilocarpine or bethanechol significantly decreased serum iPTH. This inhibition by either agent was blocked by the simultaneous administration of atropine. Administration of atropine alone significantly increased serum iPTH above baseline. This stimulation of basal serum iPTH by parasympathetic blockade suggests that even basal PTH secretion may be influenced by endogenous parasympathetic tone. Therefore, the following conclusions were reached: (1) parasympathetic influences inhibit PTH secretion, and (2) endogenous parasympathetic tone may be an inhibitory modulator of basal secretion of PTH.

A radioimmunoassay for rhesus monkey and human immunoreactive parathyrin was developed in which a selected anti-bovine parathyrin antiserum, radioiodinated purified bovine parathyrin tracer, and human parathyroid tissue-culture media standards were used. The resulting data indicate that (a) the method is sensitive, specific, accurate and reproducible; (b) it is valid for both the rhesus monkey and the human; (c) the serum immunoreactive parathyrin concentration of the monkey is essentially the same as that in man; (d) monkey immunoreactive parathyrin responds to changes in serum calcium concentration similarly to that in man; and (e) the rhesus monkey is therefore a suitable species in which to study parathyroid physiology, from which conclusions can be applied to the human.

Serum immunoreactive parathyroid hormone (iPTH) response to beta-adrenergic blockade by propranolol infusion was determined in 11 normal subjects and 6 patients with primary hyperparathyroidism (PHPT) before and again after the surgical removal of abnormal parathyroid tissue. Propranolol infusion in PHPT patients before surgery resulted in no significant decrease in serum iPTH except at 2 h, when the mean value was 83 +/- 4.4% of baseline. After surgery and achieving a euparathyroid state, the same patients showed a significant propranolol-induced decrease in serum iPTH from baseline at all time periods tested, reaching the nadir value of 57 +/- 7.5% of baseline at 2 h after the start of the propranolol infusion. This response in PHPT patients after surgery was very similar to the response seen in normal subjects. Therefore, this impaired suppressibility of serum iPTH in PHPT is corrected after removal of the abnormal parathyroid tissue. The studies indicate that abnormal parathyroid tissue (either per se or via a metabolic state induced by it) is responsible for the impaired response to beta-adrenergic blockade. It therefore appears unlikely that the impaired beta-adrenergic responsiveness is involved in the pathogenesis of PHPT.

Infusion of calcium gluconate (15 mg Ca++/kg body weight in 4 h) to 6 patients with secondary hyperparathyroidism (due to mild renal insufficiency) decreased serum parathyroid hormone (PTH) levels to the same degree (on a percent basis) as in normal subjects. Serum PTH values at 4 h were 60 +/- 4.5 (SEM)% of baseline in the patients and 59 +/- 2.9% of baseline in the normal subjects. Infusion of propranolol (1 mg i.v. bolus followed by an infusion of 60 micrograms/min for 2 h) to 7 additional patients with secondary hyperparathyroidism also decreased serum PTH to the same degree as in normal subjects. Serum PTH values at 2 h were 68 +/- 10.4% of baseline in the patients and 68 +/- 3.3% of baseline in the normal subjects. The studies indicate normal responsiveness of serum PTH to calcium or beta-adrenergic blockade in secondary hyperparathyroidism due to mild renal insufficiency.

Release of the calcitropic hormones parathyroid hormone (PTH) and calcitonin (CT) in-response to provocative stimuli was assessed in pregnant rhesus monkeys tested three times during gestation (corresponding to the end of each trimester) and again 6 weeks post partum. In the case of PTH, although basal levels were higher during pregnancy than post partum and tended to increase with advancing gestation, similar to observations in human subjects, the incremental response of the hormone to a hypocalcemic stimulus was diminished in pregnant animals and tended to lessen with advancing gestation. Basal CT levels were also increased during pregnancy but, in contrast to PTH, the incremental CT response to a provocative stimulus was generally greater during pregnancy than post partum and tended to increase with advancing gestation. The explanation of these findings may lie in differing degrees of hormone storage. These adjustments in maternal endocrine physiology regulating calcium metabolism would have the net effect of tending to preserve the maternal skeleton by protecting it from excessive resorption at times of hypocalcemia and promoting increased calcium storage during episodes of hypercalcemia.

This study evaluated the effect of somatostatin on immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) secretion in vivo in rats and monkeys and on iPTH secretion in vitro by normal bovine parathyroid tissue and by a human parathyroid adenoma. Somatostatin infusion promptly (within 0.5 h) suppressed both iPTH and iCT in both species studied in vivo, the suppression being progressive during the infusion period. In in vitro studies, somatostatin caused significant dose-related decreases in basal, low Ca-stimulated, and high Ca-suppressed PTH secretion from normal bovine parathyroid tissue and from basal and low Ca-stimulated PTH secretion from a human parathyroid adenoma. Therefore, somatostatin 1) suppresses both PTH and CT secretion in vivo; 2) acts directly on the parathyroid cell and presumably directly on the C-cell also; 3) acts upon normal and adenomatous parathyroid tissue; 4) suppresses basal, low Ca-stimulated and high Ca-suppressed PTH secretion; and 5) has a dose-related effect. The possible role of somatostatin in the physiological control of PTH and CT secretion (and therefore in Ca homeostasis), and in the pathogenesis of abnormalities of Ca homeostasis, requires further evaluation.

In vitro incubation studies with bovine parathyroid gland slices compared the relative responsiveness of parathyroid hormone (PTH) secretion to isoprotherenol, epinephrine or norepinephrine. Isoproterenol was the most potent and norepinephrine the least potent of the three stimuli, suggesting a beta 2 type of an adrenergic response. However in this in vitro system, tazalol, a selective beta 1 adrenergic agonist significantly stimulated PTH secretion, whereas terbutaline, a selective beta 2 agonist had no effect. In addition, practolol, a selective beta 1 adrenergic antagonist blocked isoproterenol- or tazolol-stimulated PTH secretion. In vivo studies in normal human subjects showed that injection of te nonselective beta agonist, isoproterenol, (0.15 mg s.c.) significantly increased, whereas injection of the selective beta 2 agonist, terbulatine (0.3 mg s.c.) had no effect on serum PTH levels. These latter studies with putative selective beta adrenergic agents suggest that the beta adrenergic receptor mediating PTH secretion is of the beta 1 type (in contrast to the studies above with nonselective agents). The studies suggest that the beta adrenergic receptor mediating PTH secretion apparently differs from the classical beta 1 receptor described in th myocardium or the classical beta 2 receptor described in the bronchial smooth muscle.

The effect of vincristine on immunoreactive parathyroid hormone (iPTH) release and parathyroid cell microtubular structures was evaluated in intact, unanaesthetized, and unrestrained rats with indwelling catheters. In overnight fasted rats, blood samples were collected before and at 30, 60 and 120 min after iv vincristine administration in low dosage (0.15 mg/kg) or in higher dosage (0.5 mg/kg) or vehicle (controls) for serum iPTH and calcium determinations. Mean baseline serum iPTH and calcium concentrations were similar in the vincristine-treated and the control rat. Following the low dose vincristine treatment, serum iPTH slightly but significantly declined to 89 +/- 5% at 30 min and remained at this low level at 60 and 120 min as compared to those observed in control rat. Similarly, iPTH concentrations after higher doses of vincristine were also significantly decreased to 87 +/- 4% at 30 min and to 83 +/- 4% at 60 min, and 86 +/- 7% at 120 min as compared to those observed in the control rat. Serum calcium concentrations were similar in the vincristine-treated and control rats. In the next study, each of the rats received vincristine and vehicle in a random order, 10 days apart. In this study also, mean serum iPTH significantly declined to 85 +/- 7% at 60 and 120 min during vincristine treatment as compared with those observed during the vehicle treatment in the same rats. Parathyroid glands were removed from rats between 60 and 120 min after vincristine or vehicle treatments for electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of histamine and histamine H2 receptors on secretion off parathyroid hormone (PTH) was evaluated by 1) adding histamine phosphate (with or without the histamine H2 receptor antagonist, cimetidine) to the medium in in vitro incubation studies with bovine parathyroid tissue, 2) infusing histamine into rats, and 3) infusing the histamine H1 receptor antagonist, diphenhydramine, or cimetidine into normal men and patients with primary hyperparathyroidism. In vitro, histamine (10(-5)-10(-7) M) caused a dose-related significant stimulation of immunoreactive PTH (iPTH) secretion; this was blocked by the simultaneous addition of cimetidine (10(-5) M). Intravenous infusion of histamine significantly increased serum iPTH in rats. In normal man, infusion of diphenhydramine had no effect, but cimetidine (300 or 450 mg) significantly decreased serum iPTH. However, cimetidine had no effect on serum iTh in primary hyperparathyroid patients. The in vitro observations indicate that histamine can stimulate iPTH secretion by a direct effect on the parathyroid cell and that this is probably a specific effect via histamine H2 receptors because the effect was blocked by the H2 receptor antagonist, cimetidine. The observed inhibition of basal PTH concentration by cimetidine induced histamine H2 receptor blockade (but not by H1 blockade) in normal human subjects suggests that endogenous histamine with H2 receptor activation stimulates even basal PTH secretion and may serve as a modulator of PTH secretion in normal man. Loss of this modulating effect of H2 receptors on PTH secretion is a characteristic of primary hyperparathyroidism.

The role of adrenergic stimuli in the secretion of parathyroid hormone (PTH) in man was evaluated. Intradermal injections of isoproterenol, 0.15 mg, or epinephrine, 0.3 mg, caused significant prompt increases in serum PTH levels. These increases were not accompanied by any changes in serum calcium (Ca) during the period of observation. Phenylephrine, 1.5 mg, intradermally, did not cause any significant changes in serum PTH or serum Ca. Propranolol infusion alone significantly inhibited the basal secretion of PTH. This inhibition by propranolol was overcome by isoproterenol administration. The results indicate that 1) beta adrenergic agents increase PTH secretion whereas alpha adrenergic agents have no effect, 2) beta adrenergic stimuli probably play an important physiological role in basal PTH secretion in man.

Previous studies have shown that estrogen therapy in postmenopausal women results in an increase in serum immunoreactive parathyroid hormone (iPTH) levels. It has been assumed that this effect of estrogen on PTH secretion is indirect, being mediated via mild hypocalcemia resulting from an inhibition of bone resorption. We evaluated the direct effect of 17 beta-estradiol (E2) and of progesterone (Prog) on secretion of PTH from bovine parathyroid tissue in vitro. Both E2 and Prog caused a significant stimulation of PTH secretion within one hour, which was progressive for the three-hour observation period. The responses were dose-related from 10(-7) to 5 X 10(-10) mol/L. There was no PTH response to 10(-7) mol/L alpha-E2, 3-methoxy estriol, estrone, testosterone, or 20-alpha-hydroxy progesterone, indicating specificity of the responses to E2 and Prog. There was a minimal PTH secretory response to 10(-6) mol/L cortisol and 10(-6) mol/L estrone. The E2 receptor antagonist tamoxifen did not inhibit the E2 effect on PTH secretion. This observation plus the rapid PTH response suggests that this hormonal effect may not be via the conventional intracellular E2 receptor. Therefore, E2 and Prog can stimulate PTH secretion by rapid, direct, and specific effects on parathyroid cells. These gonadal hormones may, therefore, be important in calcium homeostasis via their direct stimulatory effect on PTH secretion.

Our previous in vitro and in vivo studies demonstrated that exogenous somatostatin inhibited secretion of both parathyroid hormone (PTH) and calcitonin (CT). This study evaluates the possible role of endogenous somatostatin in PTH and CT secretion. Rats receiving somatostatin antiserum i.v. had significantly greater circulating levels of serum immunoreactive PTH (iPTH) and CT (iCT) than rats receiving normal rabbit serum. In in vitro studies with bovine parathyroid tissue, the addition of somatostatin antiserum to the medium significantly increased PTH secretion from basal, low calcium-stimulated and high calcium-suppressed parathyroid tissue. These combined observations strongly suggest that endogenous somatostatin must have a suppressive effect on PTH and CT secretion. The in vitro observations with isolated parathyroid tissue suggest that somatostatin is synthesized by cells within this tissue. These data strongly suggest that somatostatin is a locally-synthesized hormone that has a role in modulation of both PTH and CT secretion.

The effect of vitamin A, a membrane surface-active agent, on parathyroid hormone secretion was studied in vitro, using bovine parathyroid tissue, and in vivo in man. Parathyroid tissues were incubated with vitamin A (retinol), retinoic acid, and calcium, and with hydrocortisone and vitamin E, agents that antagonize the membrane effects of vitamin A. The stimulation of parathyroid hormone release by vitamin A, 10(-6) to 10(-9) mol/1 in vitro, was dose and time dependent. Retinoic acid did not stimulate secretion. High calcium concentration, hydrocortisone, 10(-5) mol/1 and 10(-6) mol/1, and vitamin E, 10(-5) mol/1, antagonized vitamin A-induced parathyroid hormone secretion. Vitamin A increased the lysosomal cathepsin D activity of parathyroid tissues. In human studies, eleven healthy men received two intramuscular injections of vitamin A palmitate, 25 000 units each, within 24 h. In every subject, serum parathyroid hormone increased after vitamin A administration. Our studies indicate that: (1) vitamin A stimulates parathyroid hormone secretion in vitro, possibly through modification of the cell or secretion granule membrane, or through stimulation of lysosomal proteolytic activity, and (2) vitamin A increases serum parathyroid hormone in vivo, and this effect may be important in clinical states of vitamin A excess.