Nuti K M, Karavolas H J
Department of Physiological Chemistry, University of Wisconsin, Madison 53706.
Endocrinology. 1977 Mar;100(3):777-81. doi: 10.1210/endo-100-3-777.
In an effort to determine whether the metabolic conversion of progestrone may be important in the feedback effects of this steroid, serum LH and FSH levels were measured after administration of progesterone, 5 alpha-dihydroprogesterone or 3 alpha-hydroxy-5 alpha-pregnan-20-one to estrogen-primed ovariectomized rats. A single injection of 2 or 4 mg progesterone, 4 mg 5 alpha-dihydroprogesterone, or 4 mg 3 alpha-hydroxy-5 alpha-pregnan-20-one 72 h (Day 3) after estrogen pretreatment induced a highly significant increase in serum LH and FSH 6 h later (1800 h). Although serum gonadotropin levels had begun to decrease 12 h after administration of the progestins, they were still significantly higher than control values and did not return to baseline levels until noon on Day 4. When either progesterone or 3 alpha-hydroxy-5 alpha-pregnan-20-one was administered at noon on Days 3 and 4, there was a significant reduction in LH levels 6 h after the second injection. In contrast, serum LH levels were slightly elevated 3 to 6 h (1500 to 1800 h) after the second injection of 5 alpha-dihydroprogesterone and did not decrease until 2100 h. There was no effect on FSH concentrations after a second injection of any of the progestins. Loss of uterine luminal fluid was observed within 24 h after a single injection of progesterone. Neither of the 5 alpha-reduced metabolites had an effect on uterine ballooning until after the second injection, and, even then, nonfluid-filled uteri were observed in only 20 to 30% of the animals. The results suggest that the conversion of progesterone to 5 alpha-dihydroprogesterone and 3 alpha-hydroxy-5 alpha-pregnan-20-one by neuroendocrine tissues may be necessary for the positive and negative feedback effects of progesterone on gonadotropin secretion. Thus, the diverse effects of progesterone may be due to progesterone per se (e.g., in the uterus) and/or its metabolites (e.g., in the hypothalamus and pituitary).
为了确定孕酮的代谢转化在该类固醇的反馈作用中是否重要，在给雌激素预处理的去卵巢大鼠注射孕酮、5α-二氢孕酮或3α-羟基-5α-孕烷-20-酮后，测量血清促黄体生成素（LH）和促卵泡生成素（FSH）水平。在雌激素预处理72小时（第3天）后单次注射2或4毫克孕酮、4毫克5α-二氢孕酮或4毫克3α-羟基-5α-孕烷-20-酮，6小时后（18:00）血清LH和FSH显著升高。尽管在给予孕激素后12小时血清促性腺激素水平开始下降，但仍显著高于对照值，直到第4天中午才恢复到基线水平。当在第3天和第4天中午给予孕酮或3α-羟基-5α-孕烷-20-酮时，第二次注射后6小时LH水平显著降低。相比之下，第二次注射5α-二氢孕酮后3至6小时（15:00至18:00）血清LH水平略有升高，直到21:00才下降。第二次注射任何一种孕激素后对FSH浓度均无影响。单次注射孕酮后24小时内观察到子宫腔液流失。两种5α-还原代谢物在第二次注射前对子宫膨胀均无影响，即便如此，仅20%至30%的动物观察到非充满液体的子宫。结果表明，神经内分泌组织将孕酮转化为5α-二氢孕酮和3α-羟基-5α-孕烷-20-酮可能是孕酮对促性腺激素分泌产生正负反馈作用所必需的。因此，孕酮的多种作用可能归因于孕酮本身（如在子宫中）和/或其代谢物（如在下丘脑和垂体中）。
