Hillier S G, Tetsuka M
Department of Obstetrics and Gynaecology, University of Edinburgh, UK.
Baillieres Clin Obstet Gynaecol. 1997 Jun;11(2):249-60. doi: 10.1016/s0950-3552(97)80036-3.
Androgens are products of progestogen metabolism, intermediates in oestrogen biosynthesis and local regulators of ovarian function. Current understanding of intraovarian androgen formation, metabolism and action is reviewed, highlighting the contribution of androgens to the paracrine regulation of follicular maturation and atresia. Any factor that alters intracellular cAMP levels is a potential modulator of granulosa cell differentiation, and hence follicular development. Androgen appears to modulate gonadotrophin action on granulosa cells through amplification of cAMP-mediated post-receptor signalling. Here it is argued that during intermediate stages of follicular development, locally produced androgen acts via granulosa cell androgen receptors (AR) to promote follicle-stimulating hormone (FSH)-induced granulosa cell differentiation through amplifying cAMP-mediated post-receptor signalling. During late pre-ovulatory follicular development, higher concentrations of cAMP caused by stimulation with luteinizing hormone (LH) suppress granulosa cell proliferation and down-regulate some of the genes induced by FSH at earlier stages of pre-ovulatory development, including aromatase activity. Other granulosa cell functions, including progesterone synthesis, are enhanced by the high concentrations of cAMP induced by LH. There is experimental evidence from studies of rat and non-human primate (common marmoset) ovaries that AR levels in granulosa cells decline during pre-ovulatory follicular maturation. Since androgens augment FSH-induced cAMP formation and action, loss of AR could be a means of avoiding inappropriately high cAMP levels and hence avoiding premature activation of 'high-tone' cAMP-response genes that lead to atresia. Negative regulation of the granulosa cell AR could be part of the intra-ovarian mechanism that determines which follicle(s) becomes dominant and secretes oestrogen in the normal menstrual cycle.
雄激素是孕激素代谢产物、雌激素生物合成的中间产物以及卵巢功能的局部调节因子。本文综述了目前对卵巢内雄激素生成、代谢及作用的认识，着重强调了雄激素对卵泡成熟和闭锁旁分泌调节的作用。任何改变细胞内cAMP水平的因素都是颗粒细胞分化的潜在调节因子，进而影响卵泡发育。雄激素似乎通过放大cAMP介导的受体后信号来调节促性腺激素对颗粒细胞的作用。本文认为，在卵泡发育的中间阶段，局部产生的雄激素通过颗粒细胞雄激素受体（AR）发挥作用，通过放大cAMP介导的受体后信号来促进促卵泡激素（FSH）诱导的颗粒细胞分化。在排卵前卵泡发育后期，促黄体生成素（LH）刺激导致的较高浓度cAMP会抑制颗粒细胞增殖，并下调排卵前发育早期FSH诱导的一些基因，包括芳香化酶活性。LH诱导的高浓度cAMP会增强颗粒细胞的其他功能，包括孕酮合成。对大鼠和非人灵长类动物（普通狨猴）卵巢的研究有实验证据表明，在排卵前卵泡成熟过程中，颗粒细胞中的AR水平会下降。由于雄激素会增强FSH诱导的cAMP形成和作用，AR的丧失可能是避免cAMP水平过高以及避免导致闭锁的“高调”cAMP反应基因过早激活的一种方式。颗粒细胞AR的负调节可能是卵巢内机制的一部分，该机制决定了在正常月经周期中哪些卵泡会成为优势卵泡并分泌雌激素。
