No abstract

Abstract. Hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH) has been found to stimulate human chorionic gonadotropin (hCG) secretion by trophoblast cells in vitro. To determine the biological effect of GnRH on the release of hCG in vivo, we studied the effect of the administration of GnRH on the serum levels of human chorionic gonadotropin (hCG) during pregnancy. Serum hCG levels were measured before and 15, 30, and 60 min after the intravenous administration of 100 µg of GnRH to 22 volunteers with normal pregnancy. Nine of the 12 (75%) women responded to GnRH in the first trimester, while only 1 of the 5 women (20%) responded to GnRH in the second trimester. None of the 5 women tested in the third trimester showed a significant response of hCG to the injection of GnRH. The average increase in hCG during the first, second and third trimester was 160.7± 13.5%,111.0±7.4% and 95.0±2.3%, respectively (mean ± SEM). Whereas the pregnant courses of all the cases were uneventful and normal, other abnormal pregnancies were also investigated with informed consents. Three patients with missed abortions also showed a significant response of hCG to GnRH (increase: 136.7±8.5%) when GnRH was administered before curettage of the uterine cavity. However, 4 patients with unruptured ectopic pregnancies did not respond to GnRH stimulation. These findings indicate that GnRH can stimulate the release of hCG by the placenta in vivo, consistent with the previous in vitro study, while the responsiveness depends on gestational age and the implantation site.

No abstract

Insulin-like growth factor (IGF)-I and IGF-II, and their binding proteins (IGFBPs) have been demonstrated to play important roles in follicular development as intraovarian regulators. Previous studies have demonstrated that the follicular fluid of atretic follicles contains high levels of IGFBP-2 and IGFBP-4, which are known to inhibit the action of IGFs. In this study, we identified IGFBP-4 protease activity in the follicular fluid of developing but not atretic follicles. To elucidate the regulation mechanism of IGFBP-4 proteolytic activity in the ovary, cultured luteinized granulosa cells (GCs) were incubated with various hormones, and proteolyzed IGFBP-4 in the medium was analyzed. IGFBP-4 proteolytic activity was increased when GCs were incubated with IGFs, estradiol or follicle-stimulating hormone (FSH) but not with testosterone. We also showed that IGFBP-4 inhibited IGF-I-induced estradiol release by GCs while proteolyzed IGFBP-4 did not. These results suggest that human luteinized GCs produce IGFBP-4 protease, and that FSH and IGFs may stimulate folliculogenesis by modulating IGFBP-4 degradation in the ovary.

The present study was undertaken to elucidate the physiological role and the regulation of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) in human luteinizing granulosa cells. IGFBP-1 abolished IGF-I-stimulated estradiol production by luteinizing granulosa cells in a dose-dependent manner with a 50% inhibitory concentration (IC₅₀) of 0.27 nM. Similarly, IGFBP-1 inhibited ¹²⁵I-IGF-I binding to granulosa cells. IGFBP-1 was identified by Western immunoblot and specific enzyme immunoassay in the granulosa-cell-conditioned medium after 24 h culture. Immunoreactive IGFBP-1 released into the medium was inhibited by both IGF-I and follicle-stimulating hormone dose-dependently with an IC_5o of 0.14 and 0.13 nM, respectively, while human chorionic gonadotropin-stimulated IGFBP-1 release with a 50% effective dose (ED₅₀) of 0.6 nM. These results suggest that IGFBP-1 is involved in follicular development and granulosa cell differentiation in the human ovary and that gonadotropins may influence IGF-I action by modifying IGFBP-1 levels within the ovary.