The human first-term placenta in vitro: regulation of hCG secretion by GnRH and its antagonist

Gonadotropin releasing hormone (GnRH) has been proposed to play a role in the regulation of human chorionic gonadotropin (hCG) release from the human placenta. To test this assumption, we utilized an in vitro perifusion system, together with cultures of placental explants, to investigate short- and long-term effects of GnRH and its respective antagonist on the hCG secretion from the early human placenta. Tissue slices of human placenta (100 mg), obtained from first-trimester terminations of pregnancies, were continuously perifused and the effluent collected in fractions of 2-20 min. After initial perifusion periods of 30-40 min, either GnRH, a GnRH antagonist (SB-75; Asta Pharma, Frankfurt, Germany) or both compounds at equimolar concentrations were added to the perifusion medium at final concentration of 10(-4)-10(-8) mol/l). Administration was effected either continuously or intermittently in 10-min pulses. Further, 50-mg pieces of placental tissue explants were cultured in tissue culture plates for up to 6 days. During the perifusions, hCG (determined by enzymeimmunoassay) was found to be released spontaneously in a pulsatile fashion. Pulse amplitudes and frequencies of this episodic hCG secretion were increased in response to GnRH, but not affected by GnRH antagonist. Also, GnRH stimulated the hCG secretion during cultures of placental explants. When pharmacological doses of GnRH (10(-4) mol/l) were utilized, this stimulatory effect of GnRH was no longer evident, while perifusion with medium containing GnRH antagonist at identical concentrations stimulated the hCG secretion, indicating an intrinsic agonistic activity of the antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)