REGULATION OF THE PROGESTERONE-RECEPTOR GENE BY GONADOTROPINS AND CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE IN RAT GRANULOSA-CELLS

We have examined the effects of the pituitary gonadotropins on express ion of the progesterone receptor (PR) gene in rat ovary and in granulo sa cell cultures. Both gonadotropins (LH/hCG and FSH) rapidly induce P R mRNA expression in the granulosa cells of preovulatory follicles in vivo. Gonadotropins also effectively induce PR mRNA expression in prim ary cultures of rat granulosa cells, and this action can be mimicked b y agents that elevate intracellular cAMP (forskolin or 8-bromo-cAMP). Estrogen does not induce PR mRNA expression in these cells. The cAMP-i nduced PR mRNA expression in rat granulosa cells is blocked by an inhi bitor of transcription, but not by an inhibitor of protein synthesis. Structural characterization of the rat PR gene 5'-flanking region indi cates that the proximal promoter does not contain a consensus cAMP res ponse element. However, when luciferase fusion genes containing a 1375 -basepair rat PR gene prometer were transiently transfected into rat g ranulosa cells, luciferase activity could be stimulated several-fold b y hCG or forskolin, but not by estrogen. These results indicate that g onadotropins, most likely acting through a pathway mediated by cAMP, a re able to stimulate transcription of the PR gene in rat granulosa cel ls and suggest a mechanism for regulating the intraovarian actions of progesterone.