Walter J. Henderson

Parathyroid hormone secretion: Effect of estradiol and progesterone

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.

Effect of Ethanol on Parathyroid Hormone and Calcitonin Secretion in Man

Summary Ingestion of 0.8 g/kg ethanol in 1 hr by normal man caused significant increases in both serum PTH and plasma CT concentrations, with peak values of 139% of baseline at 2 hr for PTH and of 138% at 3 hr for CT. Serum Ca did not change during the period of observation. Incubation of bovine parathyroid slices in 1.25 mM Ca Eagle media with 0.05% or 0.3% ethanol caused significant increases in PTH secretion to 122% and 166% of baseline respectively. Therefore: (1) in vitro, ethanol can be demonstrated to directly stimulate PTH secretion, (2) in vivo, ethanol ingestion induces an increase in PTH without detectable hypocalcemia, suggesting (a) prompt PTH secretion and action to compensate for a hypocalcemic effect of ethanol, so that actual hypocalcemia is not detectable, and/or (b) direct parathyroid stimulation. Though the exact mechanisms are unclear, the data indicate that ethanol, in amounts often ingested by social drinkers, increases both PTH and CT secretion, and therefore may modify Ca homeostasis.

Mechanisms of Glucocorticoid-Induced Osteopenia: Role of Parathyroid Glands

Summary Intact and PTX rats previously injected with 45Ca received cortisol, 5 mg/kg/day, for 17 weeks. Bone resorption as determined by serum and fecal 45Ca and bone 45Ca specific activity were reduced by cortisol in the PTX rats and showed a similar tendency in intact rats. In spite of this, the bone mass, as determined by ash content, was reduced by cortisol in both the intact and PTX animals. The data show that (i) cortisol, 5 mg/kg/day, produces osteopenia by inhibition of bone formation, and (ii) the presence of parathyroid glands is not essential for the production of this osteopenia. The authors thank Roberta A. Weber for her technical assistance, and Joanne C. Vaccaro for her secretarial assistance in the preparation of this manuscript.

Evidence for thyrocalcitonin in man.

Summary and conclusions The response to a hypercalcemic stimulus was studied in normal subjects and in treated hypo thyroid patients. There was no difference between the groups in the fasting plasma calcium or the plasma calcium increment immediately following the calcium infusion. However, the disappearance of the plasma calcium increment was markedly prolonged in the treated hypo-thyroid patients. These observations are interpreted as indirect evidence for the presence and homeostatic function of thyrocalcitonin in man, and a deficiency of thyrocalcitonin in patients with reduced or absent functional thyroid tissue. The full physiological significance of thyrocalcitonin in human calcium homeostasis is not clear.

Effects of vitamin D and cortisone on intestinal absorption of calcium in the rat.

Summary Using an in vitro gut sac technic, active transport of calcium through the intestinal wall of the rat has been demonstrated. In the presence of physiologic amounts of Vit. D, active calcium transport is confined to the upper portion of the small intestine. In this area, large amounts of Vit. D increase, and cortisone decreases, calcium transport. In the jejunal and ileal areas, active transport occurs only when large amounts of Vit. D are present, and this transport is not reduced by cortisone.

Effect of Hyperthyroidism on Intestinal Absorption of Calcium in the Rat.

Summary and conclusions Intestinal active transport of calcium was studied by an in vitro gut sac technic in rats with induced hyperthyroidism. An excess of thyroid hormone resulted in a prompt and persistent decrease in calcium transport, and also in a decrease of trabecular bone. The mechanism of this action of thyroid hormone and its physiologic significance is yet to be determined. It is suggested that decreased calcium absorption may be a significant factor in the negative calcium balance and bone changes found in some hyper thyroid patients.

Calcium absorption in the rat in relation to excessive vitamin D and cortisone.

Summary Calcium absorption studied in vivo was not increased by excessive Vit. D, nor decreased (actually increased) by concomitant cortisone or corticosterone administration. Active calcium transport studied in vitro was confined to the proximal small intestine, which was increased by excessive Vit. D and decreased by concomitant cortisone or corticosterone. Therefore, with the drugs, dosages, and time relationships used in this study, the in vitro intestinal sac technic is not considered a valid index of net calcium absorption in the intact animal.

Effect of the parasympathetic system on secretion of parathyroid hormone

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.

Role of endogenous somatostatin in the secretion of parathyroid hormone and calcitonin

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.

Vitamin B12 binding capacity of serum in B12 deficiency.

Summary 1. Human serum has been found to have a limited binding capacity for Vit. B12. The B12 binding protein, a seromucoid fraction, appears to be normally only approximately 30-40% saturated. In Vit. B12 deficiency the unsaturated binding capacity is normal but total binding capacity is diminished. 2. It is postulated that; the slower than normal disappearance of Co57-B12 from the plasma of B12 deficient individuals is caused by diminished binding capacity in the tissues. The authors wish to express their appreciation to Medical Illustration Service, VA West Side Hospital and to Mr. Lemuel Hall for technical assistance.