Murase Mariko, Uemura Tsuguo, Kondoh Yoshihito, Funabashi Toshiya, Hirahara Fumiki
Department of Obstetrics and Gynecology, Yokohama City University School of Medicine, Yokohama, Japan.
Endocrine. 2002 Aug;18(3):255-60. doi: 10.1385/ENDO:18:3:255.
The physiologic role of corticotropin-releasing hormone (CRH) was examined in the ovary. We investigated the effects of CRH on steroidogenesis in rat and human granulosa cells in vitro as well as the direct effects of CRH on the ovary in vivo. We further examined the gene expression of CRH in human granulosa cells. CRH significantly inhibited the production of estradiol (E2) and progesterone (P4) in rat and human granulosa cells in vitro. These inhibitory effects were completely abolished by alpha-helical CRH, a CRH receptor antagonist. Forskolin-induced increase in E2 and P4 production was attenuated by CRH. On the other hand, CRH significantly increased serum concentrations of E2 and corticosterone in vivo in hypophysectomized rats, but this increase was completely blocked by adrenalectomy. It is probable that these effects did not result from a direct action on the ovary but were an indirect effect via the adrenal gland. Finally, by reverse transcriptase polymerase chain reaction we demonstrated that CRH mRNA was expressed in human granulosa cells. Our findings indicate that CRH exerts inhibitory effects on steroidogenesis in rat and human granulosa cells, acting through the CRH receptor. These effects are attributed to cellular events downstream of cyclic adenosine monophosphate generation. CRH seems to modulate steroidogenesis via autocrine or paracrine actions in the ovary.
我们研究了促肾上腺皮质激素释放激素（CRH）在卵巢中的生理作用。我们调查了CRH对大鼠和人颗粒细胞体外类固醇生成的影响，以及CRH对体内卵巢的直接作用。我们进一步检测了人颗粒细胞中CRH的基因表达。CRH在体外显著抑制大鼠和人颗粒细胞中雌二醇（E2）和孕酮（P4）的产生。这些抑制作用被CRH受体拮抗剂α-螺旋CRH完全消除。福斯可林诱导的E2和P4产生增加被CRH减弱。另一方面，CRH在体内显著增加了垂体切除大鼠的E2和皮质酮血清浓度，但这种增加被肾上腺切除术完全阻断。这些作用可能不是直接作用于卵巢，而是通过肾上腺的间接作用。最后，通过逆转录聚合酶链反应，我们证明CRH mRNA在人颗粒细胞中表达。我们的研究结果表明，CRH通过CRH受体对大鼠和人颗粒细胞的类固醇生成发挥抑制作用。这些作用归因于环磷酸腺苷生成下游的细胞事件。CRH似乎通过卵巢中的自分泌或旁分泌作用调节类固醇生成。
