Evidence for a modulation of human chorionic gonadotropin (hCG) subunit messenger ribonucleic acid levels and hCG secretion by gamma-aminobutyric acid in human first trimester placenta in vitro.

The cytotrophoblasts are the site of production of liberins and statins in human placenta, whereas the syncytiotrophoblasts synthesize tropic hormones. These placental cell layers seem to interact like the hypothalamus and pituitary. In the central nervous system, gamma-aminobutyric acid (GABA)-ergic neurons represent one important control mechanism that seems to influence the lutropin biosynthesis indirectly (via gonadoliberin) and directly. It was the objective of the present study to find out whether GABA also may influence the biosynthesis and secretion of hCG by human first trimester placenta. Already one single pulse of GABA (1 h; 0.01-100 microM) stimulated hCG secretion significantly (P less than 0.0001). GABA also induced a marked increase in the mRNA levels of both subunits, with an optimum at 10 microM. The effect on hCG secretion was mimicked by the GABA-A receptor agonist muscimol (P less than 0.002), but under the experimental conditions used (multiple pulses; 1 microM), only the beta mRNA was increased. The GABA-A receptor antagonist bicuculline (two pulses; 10 microM) suppressed basal hCG secretion (P less than 0.001) and abolished the episodic secretion pattern observed in the control cultures. Applying a combination of equimolar amounts of GABA and bicuculline, hCG secretion and the episodic secretion pattern were similar as in control cultures. The data seem to suggest a regulation of hCG biosynthesis in human first trimester placenta in which GABA is involved, probably acting via GABA-A-like receptor sites.