Gonadotrophins inhibit and activin induces expression of inhibin/activin beta(B) subunit mRNA in cultured human granulosa-luteal cells

During the human menstrual cycle, serum inhibin concentrations fluctuate in a cyclic fashion. To examine the regulation of inhibin/activin beta (B) su bunit gene expression in ovarian granulosa-luteal cells, the levels of beta (B), subunit mRNA were determined in primary cultures of human granulosa-l uteal cells treated with gonadotrophins and protein kinase modulators. Gran ulosa cells were obtained from women undergoing an IVF programme. The cells were enzymatically dispersed, separated from red blood cells, and maintain ed in culture for 5-10 days before addition of different agents. Northern b lot analysis with specific oligonucleotide probes was performed to study in hibin/activin beta (B) subunit mRNA levels. Both LH and FSH reduced the acc umulation of beta (B) subunit mRNA in a dose-dependent manner. The protein kinase A activator, (Bu)(2)cAMP, and the protein kinase inhibitor staurospo rine also inhibited beta (B) subunit mRNA expression dose-dependently. Acti vin A increased dose-dependently beta (B) subunit mRNA expression. Our stud y suggests that activin-induced and gonadotrophin-inhibited beta (B) subuni t expression in granulosa cells might be key factors in the transition from inhibin B to inhibin A dominance during the menstrual cycle.