Summary
To investigate interactions between estrogens and calcitonin (CT), we have studied the effect of oophorectomy and estrogen replacement on plasma CT in female rats in response to an acute intravenous calcium stimulus and to hypercalcemia induced by dietary phosphorus deprivation.
Plasma CT 5 min after an intravenous calcium stimulus (10 mg Ca/kg) was 176±11 pg/ml (mean ± SEM) in rats subjected to oophorectomy compared with 244±15 pg/ml in sham-operated control rats (P<.001). Administration of estradiol benzoate (10 µg/kg/day) for 14 days restored the stimulated plasma CT concentration to 221±15 pg/ml (P<.02 compared with oophorectomy). On regression of plasma CT against calcium, including both basal and stimulated values, the slopes (± standard error of estimate) were 23.7±5.0 pg CT/mg Ca for controls, 16.1±4.0 after oophorectomy, and 26.0 ± 3.2 after estrogens. Rats placed on a low phosphorus diet demonstrated a fall in plasma phosphorus, a rise in plasma calcium, a decrease in plasma parathyroid hormone (PTH), and a rise in plasma CT after phosphorus depletion. In male rats, plasma CT was maximal on day 2 of phosphorus depletion (109±15 pg/ml vs 47±4 pg/ml for controls,P<.001), and continued phosphorus deprivation was associated with a significantly decreased plasma CT response to an intravenous calcium stimulus (mean 167±9 vs 284±21 pg/ml,P<.001). There was an inconsistent effect of oophorectomy in lowering CT levels on day 2 of phosphorus depletion and no effect on day 15 (94±19 pg/ml vs 82±9 pg/ml).
We conclude that estrogens increase the plasma CT response to an acute intravenous calcium stimulus. We examined the effect of phosphorus depletion on CT as a model for endogenous hypercalcemia. Phosphorus deprivation was found to be a potent stimulus to plasma CT, but we could not consistently demonstrate an effect of endogenous estrogens on plasma CT under these conditions (estrogen-hypophosphatemia-calcitonin).
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References
Orimo H, Fujita T, Yoshikawa M (1972) Increased sensitivity of bone to parathyroid hormone in ovariectomized rats.Endocrinology 90:760–763
Gallagher JC, Wilkinson R (1973) The effect of ethinyloestradiol on calcium and phosphorus metabolism of post-menopausal women with primary hyperparathyroidism. Clin Sci Mol Med 45:785–802
Gallagher JC, Nordin BEC (1972) Treatment with oestrogens of primary hyperparathyroidism in post-menopausal women. Lancet 1:503–5
Pak CYC, Stewart A, Kaplan R, Bone H, Notz C, Browne R (1975) Photon absorptiometric analysis of bone density in primary hyperparathyroidism. Lancet 2:7–8
Werner JA, Gorton SJ, Raisz LG (1972) Escape from inhibition of resorption in cultures of fetal bone treated with CT and parathyroid hormone. Endo 90:752–759
Atkins D, Peacock M (1975) A comparison of the effects of the calcitonins, steroid hormones, and thyroid hormones of the response of bone to parathyroid hormone in tissue culture. J Endocrinol 64:573–583
Kalu DN (1977) Acute and long-term effects of thyroidectomy on plasma calcium in rats. Endocrinology 101:1665–1669
Roos BA, Cooper CW, Frelinger AL, Deftos LJ (1978) Acute and chronic fluctuations of immunoreactive and biologically active plasma calcitonin in the rat. Endocrinology 103:2180–2186
Peng T-C, Cooper CW, Garner SC, Volpert EM (1978) Hypercalcitoninism and C-cell hyperplasia in rats with goiters produced by a low iodine diet or propylthiouracil. J Pharmacol Exp Ther 206:710
Roos BA, Deftos LJ (1976) Radioimmunoassay of calcitonin in plasma, normal thyroid, and medullary thyroid carcinoma of the rat. J Lab Clin Med 88:173
Bone HG, Onishi T, Miller M, Deftos LJ (1980) Acute, subacute, and chronic alterations of rat parathyroid hormone levels: application and validation of a radioimmunoassay. Proc Second Annual Meeting of the Amer Soc for Bone and Mineral Res, Abstract 30, p 27A
Roos BA, Deftos LJ (1979) Parathyroid hormone. In: Jaffe, BM, Behrman HR (eds) Methods of hormone radioimmunoassay. Academic Press, Inc., New York, pp 401–420
Barraclough LA (1978) Sex steroid regulation of reproductive neuroendocrine processes. In: Greep, RO, Astwood EB (eds) Handbook of Physiology. Section 7, Volume 2—“Female Reproductive System,” American Physiology Society, Washington, D.C. p 50
Hillyard CJ, Stevenson JC, MacIntyre I (1978) Relative deficiency of plasma calcitonin in normal women. Lancet 1:961
Morimoto S, Tsuji M, Okada Y, Onishi T, Kumahara Y (1980) The effect of estrogens on human calcitonin secretion after calcium infusion in elderly female subjects. Clin Endocrinol (Oxf) 13:135–144
Deftos LJ, Weisman MH, Williams GH, Karpf DB, Frumer AM, Davidson BH, Parthemore JG, Judd HL (1980) Influence of age and sex on plasma calcitonin in human beings. New Engl J Med 302:1351–1353
Heath H III, Sizemore GW (1977) Plasma calcitonin in normal man. Differences between men and women. J Clin Invest 60:1135–1140
Parthemore JG, Deftos LJ (1978) Calcitonin secretion in normal human subjects. J Clin Endocrinol Metab 47:184–188
Cressent M, Bouizar Z, Moukhtar MS, Milhaud G (1981) Effect of ovariectomy on circulating calcitonin levels in the rat. Proc Soc Exp Biol Med 166:92
Chen TL, Feldman D (1978) Distinction between alphafetoprotein and intracellular estrogen receptors: evidence against the presence of estradiol receptors in rat bone. Endocrinology 102:236
Baksi SN, Kenny AD (1977) Vitamin D3 metabolism in immature Japanese quail: effects of ovarian hormones. Endocrinology 101:1216–1220
Tanaka Y, Castillo L, DeLuca HF (1976) Control of renal vitamin D hydroxylase in birds by sex hormones. Proc Natl Acad Sci USA 73:2701–2705
Bar A, Hurwitz S (1979) The interaction between dietary calcium and gonadal hormones in their effect on plasma calcium, bone, 25-hydroxycholecalciferol-1-hydroxylase, and duodenal calcium-binding protein, measured by a radioimmunoassay in chicks. Endocrinology 104:1455–1460
Gallagher JC, Riggs BL, DeLuca HF (1980) Effect of estrogen on calcium absorption and serum vitamin D metabolites in postmenopausal osteoporosis. J Clin Endocrinol Metab 51:1359–1364
Christy NP, Shaver JC (1974) Estrogens and the kidney. Kidney Int 6:366–374
Gruin WJ, Baylink DJ, Wergedal JE (1975) Acute inhibition of mineralization and stimulation of bone resorption mediated by hypophosphatemia. Endocrinology 96:394–399
Baxter LA, DeLuca HF (1976) Stimulation of 25-hydroxy-vitamin D3-1α-hydroxylase by phosphate depletion. J Biol Chem 251:3158–3161
Gray RW, Wilz DR, Caldas AE, Lemann J Jr (1977) The importance of phosphate in regulating plasma 1,25(OH)2-vitamin D levels in humans: studies in healthy subjects, in calcium-stone formers, and in patients with primary hyperparathyroidism. J Clin Endocrinol Metab 45:299–306
Rader JE, Baylink DJ, Hughes MR, Safilian EF, Haussler MR (1979) Calcium and phosphorus deficiency in rats: effects on PTH and 1,25-dihydroxyvitamin D3. Am J Physiol 236:E118–122
Gray RW (1981) Dietary phosphate deprivation and plasma 1,25(OH)2 vitamin D concentration in the rat: the effect of hypophysectomy. Proc Am Soc for Bone and Mineral Research, Abstract 121, p 35A
Deftos LJ (1982) Calcitonin secretion. In: Bronner F, Coburn J (eds) Disorders of Mineral Metabolism Academic Press, New York
Lambert PL, Heath HH III, Sizemore GW (1979) Pre-and post-operative studies of plasma calcitonin in primary hyperparathyroidism. J Clin Invest 63:602–608
Becker KL, Silva OL, Wisneski LA, Cyrus J, Snider RH, Moore CF, Higgins GA (1980) Limited calcitonin reserve in hyperparathyroidism. Am J Med Sci 280:11–15
First BP, Larsen M, Deftos LJ (1980) Vitamin D3 induced hypercalcemia in the rat: the role of calcitonin and demonstration of sex differences in homeostasis. Proc of the VII Internal Conf on Calcium-Regulating Hormones, Estes Park, Colorado
Peng TC, Garner SC (1980) Sex difference in serum calcitonin level in rats as related to feeding, fasting, and age. Endocrinology 107:289–293
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Catherwood, B.D., Onishi, T. & Deftos, L.J. Effect of estrogens and phosphorus depletion on plasma calcitonin in the rat. Calcif Tissue Int 35, 502–507 (1983). https://doi.org/10.1007/BF02405084
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DOI: https://doi.org/10.1007/BF02405084