Comparative stimulatory effect of gonadotrophin releasing hormone (GnRH) and GnRH agonist upon pulsatile human chorionic gonadotrophin secretion in superfused placental explants: reversible inhibition by a GnRH antagonist

Abstract

The roles of gonadotrophin releasing hormone (GnRH) and a GnRH agonist (GnRHa) (D-Ala6-Met-Leu7-Pro-N-ethyl-amide) in controlling pulsatile human chorionic gonadotrophin (HCG) secretion by superfused placental explants in the first trimester were examined. One minute pulses of both GnRH and GnRHa had a biphasic effect upon pulsatile HCG secretion. GnRHa was maximally effective at 10(-10) M concentration, at 10(-11) M the effect was mild while at 10(-8) M, no effect was noted. GnRH exerted a maximal stimulatory effect at 10(-8) M; at 10(-10) M no effect was seen, while at 10(-7) M the effect was mildly stimulatory. This was evaluated by carrying out both a between and within channel type of analysis. The effect of a GnRH antagonist GnRH(ant) upon GnRH and GnRHa-induced HCG secretion was examined. Explants were incubated overnight with 10(-8) M GnRH(ant), which was also continuously administered during superfusion. The addition of 1-min pulses of GnRH and GnRHa during the exposure to GnRH(ant) failed to stimulate pulsatile HCG secretion. This effect was reversible since the response to GnRH was restored within 10 min after stopping GnRH(ant) administration. In addition, by the third cycle, co-administration of GnRH(ant) for 2 min together with 10(-10) M GnRHa for 1 min completely blocked the GnRHa-induced effect. Continuous administration of 10(-8) M GnRH(ant) decreased spontaneous HCG pulse amplitude and the area under the curve but failed to modify pulse frequency. In conclusion, GnRH appears to exert a receptor-dependent stimulatory effect upon pulsatile HCG secretion in superfusion in the first trimester placenta.(ABSTRACT TRUNCATED AT 250 WORDS)