The Effects of GnRH Agonist on Steroidogenesis in the Rat Ovary

Abstract

The effects of GnRH agonist (buserelin) on in vitro ovarian steroidogenesis were studied using DES-treated immature rats and PMS-treated immature rats. The estradiol and progesterone secreted by the cultured ovarian cells and the activities of various enzymes of steroid-metabolism were examined with or without gonadotropins (FSH or hCG), and the effects of 10^-6-10^-12M of buserelin on those indices were observed for 3-72 hours. In addition, the kinetic study of ovarian GnRH receptor was performed using ¹²⁵I-labelled buserelin and crude ovarian cell membrane fraction of PMS-treated rats. The Scatchard analysis revealed the specific high affinity and low capacity ovarian GnRH receptor (Kd=0.92nM and Bmax=0.57fmol/mg tissue). The FSH-stimulated cholesterol side chain cleavage enzyme (CSCC) activity of the DES-treated rats was suppressed in a dose-dependent manner by buserelin. Estradiol release and aromatase activity were increased by 10^-8M buserelin within 48 hours from the beginning of the incubation of the PMS-treated rat ovarian cells, but were suppressed after 48 hours. Buserelin increased basal progesterone secretion and both activities of CSCC and of 3 β-hydroxysteroid dehydrogenase of PMS-treated rat ovarian cells incubated without hCG, which were suppressed by buserelin co-incubated with 100IU/ml of hCG. These results suggested that GnRH plays a physiological role in ovarian steroidogenesis binding the specific receptor and that GnRH promotes the development of the follicle through increased estrogen synthesis in the early stage of the folliculogenesis and the luteinization in the late stage of the follicular development through increased progesterone and decreased estradiol production and the luteolysis in the luteinized cells by hCG through decreased progesterone secretion.