Spicer L J, Hammond J M
Department of Animal Science, Oklahoma State University, Stillwater 74078.
J Steroid Biochem. 1989 Oct;33(4A):489-501. doi: 10.1016/0022-4731(89)90033-2.
Development of the ovarian follicle(s) destined for ovulation appears to be a process in which antral follicles undergo a recruitment, selection and subsequent dominance phase. Several intraovarian or autocrine/paracrine regulatory mechanisms have been evoked to explain these processes. One of these potential autocrine/paracrine regulators is a catecholestrogen, 2-hydroxy-estradiol (2-OH-E2). Evidence implicating 2-OH-E2 as an autocrine/paracrine regulator of follicular function is reviewed. Studies have shown 2-OH-E2 to be present in nanomolar concentrations in fluid of human and equine follicles. In addition, the enzyme responsible for converting estradiol (E2) into 2-OH-E2, estrogen 2-hydroxylase (E-2-H), is abundant in granulosa and thecal cells (but not corpora lutea) of porcine follicles. Moreover, activity of E-2-H increases during follicular development in pigs. In vitro, the actions of 2-OH-E2 have been compared to those of E2, gonadotropins, catecholamines, and androgens. Studies indicated that the maximal stimulatory effects of 2-OH-E2 on progesterone production were comparable to those of E2 and gonadotropins, and greater than androgens or catecholamines. The effect of 2-OH-E2 was found to be significantly additive to each of the other classes of compounds at maximally effective concentrations, suggesting that the mechanism of action of 2-OH-E2 was different. The mode of action of the several stimulators of progesterone biosynthesis were examined additionally with antihormones for E2, catecholamines, and androgens. In each instance, the hormonal antagonists were able to inhibit the action of the predicted class of effector compounds. However, with the exception of the antiandrogen, hydroxyflutamide, no effects of anti-hormones on the action of 2-OH-E2 were observed. In the aggregate, these studies suggested that the action of 2-OH-E2 is mediated by a mechanism discrete from those of the other classes of hormones examined to date, and that hydroxyflutamide exhibits both antiandrogen and anticatecholestrogen activity. 2-OH-E2 can also enhance the actions of other trophic hormones, epinephrine, LH and FSH, by enhancing hormone-stimulated cAMP production. This effect on epinephrine action appears to be due to a 2-OH-E2-stimulated increase in the density of beta-adrenergic receptors. Whether 2-OH-E2 stimulates an increase in the number of LH and FSH receptors remains to be determined. The precise locus of the stimulatory effect of 2-OH-E2 alone on steroidogenesis is unclear but preliminary data would suggest that 2-OH-E2 may be stimulating side-chain cleavage enzyme activity.(ABSTRACT TRUNCATED AT 400 WORDS)
注定要排卵的卵巢卵泡的发育似乎是一个窦状卵泡经历募集、选择及随后的优势化阶段的过程。人们已经提出了几种卵巢内或自分泌/旁分泌调节机制来解释这些过程。其中一种潜在的自分泌/旁分泌调节因子是儿茶酚雌激素2-羟基雌二醇（2-OH-E2）。本文综述了将2-OH-E2作为卵泡功能自分泌/旁分泌调节因子的相关证据。研究表明，2-OH-E2以纳摩尔浓度存在于人类和马卵泡液中。此外，负责将雌二醇（E2）转化为2-OH-E2的酶——雌激素2-羟化酶（E-2-H），在猪卵泡的颗粒细胞和卵泡膜细胞（但不包括黄体）中大量存在。而且，猪卵泡发育过程中E-2-H的活性会增加。在体外，已将2-OH-E2的作用与E2、促性腺激素、儿茶酚胺和雄激素的作用进行了比较。研究表明，2-OH-E2对孕酮生成的最大刺激作用与E2和促性腺激素相当，且大于雄激素或儿茶酚胺。发现在最大有效浓度下，2-OH-E2的作用与其他各类化合物的作用具有显著的相加性，这表明2-OH-E2的作用机制不同。还使用E2、儿茶酚胺和雄激素的抗激素对几种孕酮生物合成刺激剂的作用方式进行了研究。在每种情况下，激素拮抗剂都能够抑制预期的效应化合物类别的作用。然而，除了抗雄激素羟基氟他胺外，未观察到抗激素对2-OH-E2作用的影响。总体而言，这些研究表明，2-OH-E2的作用是由一种与迄今为止所研究的其他激素类别不同的机制介导的，并且羟基氟他胺具有抗雄激素和抗儿茶酚雌激素活性。2-OH-E2还可以通过增强激素刺激的环磷酸腺苷（cAMP）生成来增强其他营养激素、肾上腺素、促黄体生成素（LH）和促卵泡生成素（FSH）的作用。这种对肾上腺素作用的影响似乎是由于2-OH-E2刺激β-肾上腺素能受体密度增加所致。2-OH-E2是否会刺激LH和FSH受体数量增加仍有待确定。2-OH-E2单独对类固醇生成的刺激作用的确切位点尚不清楚，但初步数据表明2-OH-E2可能在刺激侧链裂解酶活性。（摘要截选至400字）
