Glucocorticoids possess calcitonin-like antihypercalcemic properties in rats.
The interaction among parathyroid hormone (PTH), calcitonin (CT), and glucocorticoids on blood calcium (Ca) was examined. Prior studies had shown that adrenalectomy (ADX) reduced the fall in blood calcium in rats after parathyroidectomy (PTX). Convincing evidence was provided showing that the ADX effect in PTX rats was due to the loss of corticosterone, the major glucocorticoid in rats; restoring physiological blood levels of corticosterone abolished the ADX effect in PTX rats. The initial attempt of the present study was to explain the failure of ADX or exogenous glucocorticoids to alter serum Ca levels in rats with intact thyroid and parathyroid glands or in thyroidectomized rats with functional parathyroid transplants (PTT). We found, as previously reported, that the 5-h level of serum Ca in rats with parathyroid glands was not affected by s.c. hydrocortisone (cortisol) or by ADX. It was also not affected by thyroparathyroidectomy (TPTX) or after both ADX and TPTX in rats with PTT. These results suggested to us that the glucocorticoid effect to lower serum was inhibited by endogenous parathyroid hormone (PTH) from the parathyroid gland and/or by normal levels of blood Ca. Both of these proposed mechanisms were examined and failed to explain the absence of the ADX effect as well as the glucocorticoid effect in normocalcemic parathyroid-intact rats, because an ADX effect was observed in TPTX rats given hypercalcemic doses of rat or bovine PTH 1-34 or calcitriol. Also, administered cortisol restricted the increased hypercalcemia induced by PTH in ADX-TPTX rats. Expanding on the results in TPTX rats with induced hypercalcemia, we found that neither the ADX effect nor the glucocorticoid effect occurred in thyroid-intact rats with or without functional PTT. These as well as previous results show that: 1. Glucocorticoids, like CT, restrict hypercalcemia in TPTX rats. 2. The ADX effect and its reversal by glucocorticoids in rats with induced hypercalcemia occur only in the absence of the thyroid gland (removal of CT). 3. Glucocorticoids, like CT, lower serum calcium during the hypocalcemia after PTX, an effect that occurs in the presence or absence of the thyroid gland. This study did not reveal why neither ADX nor exogenous glucocorticoids altered serum calcium levels in normocalcemic rats with either intact parathyroid glands or PTT. We conclude that under appropriate conditions, glucocorticoids act in a fashion similar to that of CT in restricting hypercalcemia and in lowering blood Ca.
Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27599-7455, USA. pfhirsch@med.unc.edu.us
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Hirsch
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Imai
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Hosoya
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Ode
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Maeda
D000315:Adrenalectomy; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D002118:Calcium / Q000097:blood*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D016105:Parathyroidectomy; D051381:Rats; D019379:Teriparatide / Q000494:pharmacology; D013965:Thyroidectomy
D005938:Glucocorticoids; D010281:Parathyroid Hormone; D019379:Teriparatide; D002116:Calcitonin; D002118:Calcium; D006854:Hydrocortisone