Factors controlling spontaneous human chorionic gonadotrophin in superfused first trimester placental explants

Abstract

We have recently reported that secretion of human chorionic gonadotrophin (HCG) by placental explants in superfusion is pulsatile. In this study, the factors involved in regulation of spontaneous pulsatility were examined. In superfusion, observed secretion of HCG by isolated cells was continuous, without spontaneous episodic hormonal secretion. However, this was not due to diminished viability of the cells since these cells continued to secrete sex steroids. In addition, the stimulatory response of HCG to a highly effective dose of 10(-9) M gonadotrophin releasing hormone (GnRH) analogue was also maintained. Preincubation of explants with low concentrations of cycloheximide (10(-6)M) markedly reduced baseline HCG levels as well as pulse amplitude, suggesting that episodic hormone secretion is in part dependent on protein synthesis. Moreover, preincubation of explants with labelled leucine has shown that the secretion of placental proteins is also episodic in superfusion. The pattern was similar but not identical to that of HCG. Addition of 1 min pulses of CaCl2 caused a significant release of HCG by superfused explants, suggesting that HCG secretion occurs through the release of storage granules. It was concluded that for the expression of spontaneous pulsatile secretion of HCG cell to cell contact/communication is necessary. HCG secretion is likely to reflect exocytosis of storage granules. HCG pulsatility is partly dependent on protein synthesis and this intermittent type of secretion can be documented by overall protein secretion by the superfused explant.