Possible interactions between leptin,gonadotrophin-releasing hormone (GnRH-I and II) and human chorionic gonadotrophin (hCG)

Leptin is a metabolic signal to the reproductive axis, where it increases the plasma levels of luteinising hormone (LH) and follicle stimulating hormone (FSH). Since the placental regulation of human chorionic gonadotrophin (hCG) mimics that of the pituitary LH, we undertook this study to see if leptin could be involved in the secretion and synthesis of hCG in first-trimester trophoblast. We incubated cytotrophoblastic cells (CTB) with GnRH-I or GnRH-II, for 4 or 48 h and collected the media at different times thereafter. GnRH-II was more potent than GnRH-I when incubated for 4 h with CTB. Leptin secretion, as measured at 4 h, was significantly stimulated by GnRH-II. When measured at 24 h leptin values were also increased as compared to controls. Neither GnRH-I, nor GnRH-II had any effect on leptin secretion when incubated for 48 h with CTB. Leptin was also added to perifused placental explants, and samples (in which hCG was measured) were collected every 3 min. Leptin significantly stimulated hCG secretion by explants and induced a pulse of hCG immediately (within 6 min) after its injection, increasing significantly the area under the curve (P=0.04) and the amplitude (P=0.02) of hCG pulses. We conclude that GnRH-II is more effective than GnRH-I in stimulating leptin secretion. This difference could be explained by the existence of two different types of placental GnRH receptors or two different pathways of GnRH degradation. Furthermore, we observe that leptin has a significant stimulatory effect on hCG pulsatility.