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.

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The biological activity of several 3:5-diiodo-3'- and 3':5'-alkyl and arylthyronines as well as of some 3:5-diiodo-3'-isopropylthyroacetic acid analogues was determined following their subcutaneous administration to adult male rats. l(+) 3:5:3'-triiodothyronine (l-triiodothyronine) was used as the reference compound. l(+) 3:5-Diiodo-3'-isopropylthyronine was the only compound in this series found to be more active than l-triiodothyronine in all of the assays that were performed. It exhibited twice the calorigenic, 1.3 times the cholesterol-lowering, 1.8 times the antigoitrogenic, and 1.4 times the heart weight-increasing activity of the reference agent. This is the first thyromimetic substance reported to be more active in rats than the endogenous thyroid hormones. Each experiment consisted of injecting at least four doses of the agent to be assayed as well as of l-triiodothyronine to different groups of rats. The resulting data were evaluated statistically. Photographs of Courtald atomic models of several alkyl thyronines are presented for the purpose of indicating the possible importance of the relative "bulk" of the alkyl constituents compared to that of the iodine atom in the 3'-position.

Benzoyluracil (V) (0.075 g., 0.25 mole) was added to a solution of potassium borohydride (0.037 g.) in 2 ml. of water. The mixture was stirred vigorously for about 10 min. at room temperature and then for a further 5 min. at 100°. On acidifying with 3 .V hydrochloric acid and cooling in ice there was obtained 0.03 g. (40%) of a white solid.