A functional bone morphogenetic protein system in the ovary

Bone morphogenetic proteins (BMPs) comprise a large group of polypeptides i n the transforming growth factor beta superfamily with essential physiologi cal functions in morphogenesis and organogenesis in both vertebrates and in vertebrates, lit present, the role of BMPs in the reproductive system of an y species is poorly understood. Here, we have established the existence of a functional BMP system in the ovary, replete with ligand receptor, and nov el cellular functions. In situ hybridization histochemistry identified stro ng mRNA labeling for BMP-4 and -7 in the theca cells and BMP receptor types IA IB, and II in the granulosa cells and oocytes of most follicles in ovar ies of normal cycling rats, To explore the paracrine function of this BMP s ystem, ne examined the effects of recombinant BMP-4 and -7 on FSH (follicle -stimulating hormone)-induced rat granulosa cytodifferentiation in serum-fr ee medium. Bath BMP-4 and -7 regulated FSH action in positive and negative ways. Specifically, physiological concentrations of the BMPs enhanced and a ttenuated the stimulatory action of FSH on estradiol and progesterone produ ction, respectively, These effects were dose- and time-dependent. Furthermo re, the BMPs increased granulosa cell sensitivity to FSH, Thus, BMPs have n ow been identified as molecules that differentially regulate FSH-dependent estradiol and progesterone production in a,way that reflects steroidogenesi s during the normal estrous cycle. As such, it can be hypothesized that BMP s might be the long-sought "luteinization inhibitor" in Graafian follicles during their growth and development.