Prostaglandin E2 induces inhibin α- and βA-subunit mRNA and secretion of dimeric inhibin A in cultured human granulosa-luteal cells

Prostaglandins (PG) E-2 and F-2 alpha, are produced by the human corpus luteum in significant amounts and they are known to exert local luteotrophic and luteolytic effects respectively. The present study determined how PGF(2 alpha) and PGF(2 alpha )are involved in the regulation of inhibin A, a granulosa cell-derived glycoprotein hormone that has an endocrine inhibitory effect on hypophyseal gonadotrophin production and a local stimulatory action on thecal cell androgen secretion. The effects of PGE(2) and PGF(2 alpha )on inhibin alpha- and beta(A)-subunit mRNAs levels and on the secretion of dimeric inhibin A were studied in cultures of human granulosa-luteal cells obtained from patients undergoing an in-vitro fertilization programme. We found that PGE(2) induced mRNA of inhibin alpha- and beta(A)-subunits in a time- and concentration dependent manner, whereas PGF(2 alpha) had no clear effect. In contrast to the rapidly and transiently induced IS A -subunit mRNA, alpha-subunit mRNA accumulation was stimulated with slower kinetics by PGE(2) in a protein synthesis-dependent manner; this was also observed for the mRNA of the cytochrome P450scc enzyme. In the medium of cells cultured for 24 h with PGE(2) (1x10(-6) M), a 1.3-1.6-fold increase (P <0.05) above basal values in secreted dimeric inhibin A was observed. The results suggest that PGE(2) is an important inducer of inhibin A production in granulosa cells and that a local action of PGE(2) may partially explain the increase in circulating inhibin A observed during the midluteal phase of the human menstrual cycle.