Ghizzoni L, Mastorakos G, Vottero A, Barreca A, Furlini M, Cesarone A, Ferrari B, Chrousos G P, Bernasconi S
Department of Pediatrics, University of Parma, Italy.
Endocrinology. 1997 Nov;138(11):4806-11. doi: 10.1210/endo.138.11.5474.
The presence of immunoreactive CRH was recently demonstrated in human ovaries. CRH immunoreactivity was localized by immunohistochemistry in the cytoplasm of thecal cells surrounding the ovarian follicles, in luteinized cells of the stroma, and in large granulosa-derived luteinized cells of developing corpora lutea. Also, CRH and its receptors were identified in Leydig cells of the testis where CRH was shown to inhibit testosterone biosynthesis. To examine the role of CRH in the ovary, we studied its effect on estradiol (E2) and progesterone (P4) release by human granulosa cells obtained from women undergoing in vitro fertilization for male factor infertility or uni- or bilateral tubal impatency. In all subjects, superovulation was induced by treatment with gonadotropins. The effects of graded doses of ovine CRH (10[-11]-10[-6] mol/liter) were evaluated in the conditioned medium obtained after 24 h incubation of the cells. All CRH concentrations employed except for the lowest one (10[-11] mol/liter) caused a significant decrease of media E2 and P4 levels. Maximal inhibition for both E2 and P4 production was obtained by 10[-6] mol/liter CRH concentration, which decreased hormone production by 39% and 34%, respectively. The alpha-helical CRH9-41 antagonist at 10(-6) and 10(-7) mol/liter blocked the suppressive effect of 10(-9) mol/liter CRH on both E2 and P4 secretion, while it had no effect when added to the culture media without CRH. Since interleukin (IL-1)-1 mediates certain actions of CRH on leukocytes, we examined whether the CRH effect on ovarian steroidogenesis was IL-1-mediated. Interleukin-1 receptor antagonist at 10(-7) and 10(-6) mol/liter blocked the inhibitory effects of CRH on E2 and P4 secretion, while it had no effect in the absence of CRH. In conclusion, CRH exerts a CRH- and IL-1 receptor-mediated inhibitory effect on ovarian steroidogenesis and might be actively involved in the still enigmatic processes of follicular atresia and luteolysis.
最近在人类卵巢中发现了免疫反应性促肾上腺皮质激素释放激素（CRH）。通过免疫组织化学方法，CRH免疫反应性定位于卵巢卵泡周围的膜细胞、基质的黄体化细胞以及发育中的黄体中由颗粒细胞衍生的大型黄体化细胞的细胞质中。此外，在睾丸的间质细胞中也鉴定出了CRH及其受体，其中CRH被证明可抑制睾酮的生物合成。为了研究CRH在卵巢中的作用，我们研究了其对从因男性因素不育或单侧或双侧输卵管不通而接受体外受精的女性获得的人颗粒细胞释放雌二醇（E2）和孕酮（P4）的影响。在所有受试者中，通过促性腺激素治疗诱导超排卵。在细胞培养24小时后获得的条件培养基中评估了不同剂量（10[-11]-10[-6]摩尔/升）的绵羊CRH的作用。除最低剂量（10[-11]摩尔/升）外，所有使用的CRH浓度均导致培养基中E2和P4水平显著降低。10[-6]摩尔/升的CRH浓度对E2和P4产生的抑制作用最大，分别使激素产生减少39%和34%。10(-6)和10(-7)摩尔/升的α-螺旋CRH9-41拮抗剂可阻断10(-9)摩尔/升CRH对E2和P4分泌的抑制作用，而将其添加到不含CRH的培养基中则无作用。由于白细胞介素（IL-1）-1介导CRH对白细胞的某些作用，我们研究了CRH对卵巢类固醇生成的作用是否由IL-1介导。10(-7)和10(-6)摩尔/升的白细胞介素-1受体拮抗剂可阻断CRH对E2和P4分泌的抑制作用，而在没有CRH的情况下则无作用。总之，CRH对卵巢类固醇生成具有CRH和IL-1受体介导的抑制作用，可能积极参与卵泡闭锁和黄体溶解这两个仍不清楚的过程。
