ACUTE STIMULATION OF HUMAN CHORIONIC-GONADOTROPIN SECRETION BY RECOMBINANT HUMAN ACTIVIN-A IN 1ST TRIMESTER HUMAN TROPHOBLAST

Inhibin and activin are synthesized by the placenta, raising questions as to their functions in this tissue. The possibility of local regulation of other placental hormones critical during pregnancy was investigated by examining the effects of recombinant human inhibin-A and activin-A on hCG secretion. Potential interactions with GnRH-stimulated hCG secretion were also explored. First trimester human placental tissue was physically dissociated to isolate trophoblast cells. Cells were cultured on microcarrier beads for 7-10 days and loaded into 1.5-ml chambers in a perifusion system. After a 1-h control period, hormone treatments were administered in the perifusion medium for 5 min, and perifusate was collected for an additional 55 min. Perifusate fractions were analyzed for hCG concentration by RIA. Both activin and GnRH stimulated a rapid and transient hCG secretory response in the perifusion system. Unlike the effect of GnRH, the activin-stimulated hCG response was not blocked by concomitant treatment with a GnRH antagonist. The hCG RIA results were confirmed by preliminary experiments using a novel hCG bioassay. This suggested that activin did not facilitate hCG secretion by stimulation of endogenous GnRH release. Inhibin alone did not affect hCG secretion or GnRH-stimulated hCG secretion. However, treatment with inhibin and activin in combination resulted in a transient increase in hCG, followed by a decrease in hCG secretion to below pretreatment levels. The results suggested that in addition to GnRH, activin may play a role in the regulation of hCG secretion in first trimester placenta.