Mahesh V B, Mills T M, Bagnell C A, Conway B A
Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912.
Adv Exp Med Biol. 1987;219:237-57. doi: 10.1007/978-1-4684-5395-9_12.
In the human, polycystic ovaries are generally accompanied by normal or elevated levels of serum LH, normal or slightly depressed FSH and by high levels of circulating estrogens and androgens. If the excess androgen secretion is reduced by one of several methods, ovulatory cycles are usually restored. Several animal model systems have been proposed for the study of the pathophysiology of the polycystic ovarian syndrome. These include neonatal androgenization, hCG administration to hypothyroid rats, injection of estradiol valerate and maintaining animals in constant light. In a model developed in this laboratory, pubertal or adult rats were treated with the weak androgen, dehydroepiandrosterone (DHA), to induce polycystic ovaries. This treatment also altered the blood levels of LH and FSH but the effect on gonadotropins and on the formation of the degenerative follicles was fully reversed following discontinuation of the androgen injections. The polycystic ovaries of the DHA-treated animals were steroidogenically more active than controls raising the possibility that the DHA was acting directly on the ovary in addition to an action on the pituitary-hypothalamus axis. In order to study the direct effect of androgens on the ovary, another animal model was developed in which immature, hypophysectomized rats were injected with pregnant mare serum gonadotropin (PMSG) to initiate follicular growth followed by a single injection of dihydrotestosterone (DHT). The androgen caused follicular atresia and decreased the number of ova shed in response to ovulation induction with hCG. The suppressive effects of DHT were entirely prevented by concomitant treatment with estradiol. The studies with DHT were continued using another batch of PMSG, but the DHT-induced increase in the rat of atresia and suppression of induced ovulation were no longer seen. However, when this same batch of PMSG was given with estrogen or with the antiandrogen flutamide, there was less atresia and the growth of follicles was actually enhanced. Based on these studies, it was postulated that the second batch of PMSG had greater LH activity than the first preparation and that the LH has stimulated endogenous androgen production. The ovarian follicles which appeared to be most susceptible to this DHT effect were small to medium in size and had a low capacity to synthesize estrogen. This possibility was confirmed in another animal model system in which immature rats were injected with PMSG and 4 separate injections of DHT and then sacrificed at several time points over the next 8 days.(ABSTRACT TRUNCATED AT 400 WORDS)
在人类中，多囊卵巢通常伴有血清促黄体生成素（LH）水平正常或升高、促卵泡生成素（FSH）水平正常或略有降低，以及循环雌激素和雄激素水平升高。如果通过几种方法之一降低雄激素分泌过多的情况，排卵周期通常会恢复。已经提出了几种动物模型系统用于研究多囊卵巢综合征的病理生理学。这些包括新生儿雄激素化、对甲状腺功能减退大鼠注射人绒毛膜促性腺激素（hCG）、注射戊酸雌二醇以及使动物处于持续光照下。在本实验室开发的一个模型中，对青春期或成年大鼠用弱雄激素脱氢表雄酮（DHA）进行处理以诱导多囊卵巢。这种处理也改变了LH和FSH的血液水平，但在停止雄激素注射后，对促性腺激素和退化卵泡形成的影响完全逆转。经DHA处理的动物的多囊卵巢在类固醇生成方面比对照更活跃，这增加了DHA除了对垂体 - 下丘脑轴有作用外还直接作用于卵巢的可能性。为了研究雄激素对卵巢的直接作用，开发了另一种动物模型，其中对未成熟的垂体切除大鼠注射孕马血清促性腺激素（PMSG）以启动卵泡生长，随后单次注射双氢睾酮（DHT）。雄激素导致卵泡闭锁，并减少了用hCG诱导排卵时排出的卵子数量。双氢睾酮的抑制作用通过同时用雌二醇处理而完全被阻止。使用另一批PMSG继续进行双氢睾酮的研究，但不再观察到双氢睾酮诱导的大鼠闭锁增加和诱导排卵的抑制。然而，当将同一批PMSG与雌激素或抗雄激素氟他胺一起给予时，闭锁减少，卵泡生长实际上得到增强。基于这些研究，推测第二批PMSG比第一批制剂具有更高的LH活性，并且LH刺激了内源性雄激素的产生。似乎对这种双氢睾酮作用最敏感的卵巢卵泡大小为小到中等，合成雌激素的能力较低。在另一种动物模型系统中证实了这种可能性，在该系统中，对未成熟大鼠注射PMSG和4次单独的双氢睾酮注射，然后在接下来的8天内的几个时间点处死。（摘要截断于400字）
