Effect of estrogens and phosphorus depletion on plasma calcitonin in the rat

Abstract

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

The thyroid C cells of ovariectomized rats treated with estradiol

“…These results suggest that estrogen has a positive effect on C cell secretory activity. Other studies also confirmed that ovariectomized animals have diminished basal CT secretion and that estrogen supplement therapy throughout the period of estrogen deficiency prevents a reduction of CT secretion (Catherwood et al 1983;Yamazaki and Kinoshita 1986;Grauer et al 1993). Moreover, Greenberg et al (1986) showed that 17b estradiol promptly stimulated CT secretion from rat thyroid glands in vitro in a dose-related manner.…”

“…On the contrary, morphometric data and subcellular organization of C cells in castrated pigs suggested stimulation of specific protein synthesis (Sekulić and Lovren 1995). Nevertheless, estrogen treatment of ovariectomized (Ovx) rats and women was found to have a stimulatory effect on secretion of CT (Catherwood et al 1983;Yamazaki and Kinoshita 1986;Isaia et al 1992;Grauer et al 1993). However, other authors showed no effect of estrogen replacement therapy (Selby and Peacock 1986) or inducement of a slight reduction in basal CT levels in postmenopausal women (Body 1993).…”

The effects of sex steroids on thyroid C cells and trabecular bone structure in the rat model of male osteoporosis

“…On the other hand, several studies have shown that estrogen treatment stimulates CT secretion in Ovx rats (Catherwood et al. ; Filipović et al. ) and women (Isaia et al.…”

Effects of 17β-estradiol on calcitonin and calcitonin-gene-related peptide secretions and contents in a murine medullary thyroid carcinoma C-cell line (CA-77)

“…Several investigators have shown that the circulating concentrations of CT are decreased in the oophorectomized or postmenopausal state (Milhaud et al, 1978), and that estrogen increases CT secretion (Morimoto et al, 1980). In oophorectomized rats, the plasma CT response to a calcium challenge is impaired and can be restored to normal levels by estrogen replacement therapy (Catherwood et al, 1983). Rat pup thyroid incubation studies demonstrate that estradiol can stimulate CT secretion in vitro (Greenberg et al, 1986).…”