Greenberg C, Kukreja S C, Bowser E N, Hargis G K, Henderson W J, Williams G A
Endocrinology. 1986 Jun;118(6):2594-8. doi: 10.1210/endo-118-6-2594.
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.
雌激素疗法已被用于抑制绝经后女性的骨吸收并预防骨质疏松症。以往的研究对于雌激素作用机制是否涉及刺激降钙素(CT)分泌存在分歧。我们在体外评估了17β-雌二醇(E2)和孕酮(Prog)对8日龄大鼠甲状腺C细胞CT分泌的直接影响。E2和Prog在1小时内均显著刺激CT分泌,在3小时的观察期内这种刺激呈进行性。在10^(-7)至5×10^(-10) M范围内,反应呈剂量相关。对于10^(-7) M的α-雌二醇、雌三醇、3-甲氧基雌三醇、雌酮睾酮或20α-羟孕酮无CT反应,表明对E2和Prog反应具有特异性。对于10^(-6) M皮质醇,CT分泌反应极小。E2受体拮抗剂他莫昔芬不抑制E2对CT分泌的作用。这一观察结果加上快速的CT反应表明,这种激素效应可能不是通过传统的细胞内E2受体介导的。因此,E2和Prog可通过对甲状腺C细胞的快速、直接和特异性作用刺激CT分泌。因此,性腺激素可能通过其对CT分泌的直接刺激作用在抑制骨吸收方面发挥重要作用。