Effects of Estradiol and Progesterone on Calcitonin Secretion*

Abstract

Estrogen therapy has been used to inhibit bone resorption and prevent osteoporosis in postmenopausal women. Previous studies have disagreed as to whether the mechanism of estrogen action involves stimulation of calcitonin (CT) secretion. We evaluated the direct effects of 17 beta-estradiol (E2) and progesterone (Prog) on CT secretion from the thyroid C cells of 8-day-old rats in vitro. Both E2 and Prog caused a significant stimulation of CT secretion within 1 h, which was progressive for the 3-h observation period. The responses were dose related from 10(-7) to 5 X 10(-10) M. There was no CT response to 10(-7) M alpha-estradiol, estriol, 3-methoxyestriol, estrone, testosterone, or 20 alpha-hydroxyprogesterone, indicating specificity of the responses to E2 and Prog. There was a minimal CT secretory response to 10(-6) M cortisol. The E2 receptor antagonist tamoxifen did not inhibit the E2 effect on CT secretion. This observation plus the rapid CT response suggest that this hormonal effect may not be via the conventional intracellular E2 receptor. Therefore, E2 and Prog can stimulate CT secretion by rapid, direct, and specific effects on the thyroid C cell. The gonadal hormones may, therefore, be important in inhibiting bone resorption via their direct stimulatory effect on CT secretion.

Estrogen receptors and biologic response in rat parathyroid tissue and C cells.

“…The action of estradiol to increase the expression of the PTH and calcitonin genes, and the presence ofthe estrogen receptor mRNA and protein in the parathyroid and C cells, as shown in this study, together with the earlier reports of a direct effect of estrogens to increase PTH and calcitonin secretion (16)(17)(18)(19) establish that these two organs are target organs for estrogens.…”

“…Our results, together with the earlier in vitro reports of a direct effect of estrogens on PTH and calcitonin secretion (16)(17)(18)(19), indicate that the effect of estrogens to increase PTH and calcitonin levels is a direct effect ofestrogens on the parathyroid and C cells, respectively. In addition we have preliminary data with bovine parathyroid cells in primary culture, and a calcitonin producing cell line, that estrogens in vitro increase PTH and calcitonin mRNA levels, respectively (Naveh-Many, T., and J.…”

“…Estrogens might also have an indirect effect on bone by regulating the production of the calcium regulating hormones. In vitro studies have shown that estrogens increase the secretion of PTH from both bovine and human parathyroid tissue, and increase the secretion ofcalcitonin from a medullary carcinoma cell line (16)(17)(18)(19). We have now studied the regulation of PTH and calcitonin gene expression in vivo in the rat, and the presence ofthe estrogen receptor mRNA and protein in the rat parathyroid and C cells.…”

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)

“…The dose of 17(3-estradiol used in the present in vitro studies (100 nmol/I) was shown to achieve a maximal increase of CT secretion by thyroparathyroid gland complexes of 8-d-old rat pups (Greenberg et al, 1986) (Naveh-Many et al, 1992), and also with the fact that estradiol given to ovariectomized animals prevents the decrease in CT mRNA levels (Naveh-Many et al, 1992;Lamari et al, 1994 (Russo et al, 1988;Collignon et al, 1992) and enhances the biosynthesis and release of both CT and CGRP (Lamari et al, 1994) in CA-77 C cells has already been reported. All-trans-retinoic acid also was shown to decrease both CT and CGRP mRNAs in CA-77 C cells and the secretion of both peptides (Lamari et al, 1994).…”

“…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). In contrast, in the human C cell carcinoma cell line (TT) with well-documented estrogen receptors, estradiol induces a dose-dependent inhibition of CT secretion (Lazaretti-Castro et al, 1991).…”