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/xg/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).Keywords: Estradiol --Hypercalcemia --Calcitonin --Oopherectomy.Estrogen and calcitonin (CT) are known to modulate bone metabolism. Estrogens antagonize the effects of parathyroid hormone in the rat [1] and in man [2-4]; CT causes hypocalcemia by inhibition of bone resorption [5,6]. Endogenous CT in the rat is effective also in controlling plasma calcium in the face of dietary calcium intake [7]. The possibility of interactions between estrogens and CT is suggested by the observation that plasma CT is greater in female than in male rats [8,9]. Therefore, we felt it was of interest to study the effect of estrogens on CT in this species. In this paper, we report our studies of the effect of oophorectomy and estradiol on plasma CT response to acute and chronically induced hypercalcemia.
Materials and MethodsSprague-Dawley rats (approximately 200 g) were alternately assigned to groups by ascending weight. Bilateral gonadectomies or sham procedures were performed under pentobarital (30-40 mg/kg) and ketamine (50 mg/kg) anesthesia. Experiments were