Multiple endocrine regulation by bone morphogenetic protein system

Bone morphogenetic proteins (BMPs) were originally identified with regard to their actions to regulate ectopic formation of bone and cartilage and early embryonic development. Subsequently, our research program has investigated a BMP system that exists in the mammalian ovary and plays roles in regulating numerous granulosa cell functions. BMP ligands including BMP-2, -4, -6, -7 and -15 were found to inhibit gondotropin-dependent progesterone synthesis by granulosa cells, which led to the hypothesis that BMPs are a physiological luteinization inhibitor in growing ovarian follicles during the follicular phase of the ovarian cycle. The physiological importance of the BMP system for normal mammalian reproduction has been further recognized by the discovery of aberrant reproductive phenotypes of female sheep and humans having mutated genes encoding BMP-15. Physiological roles of BMPs in the pituitary, hypothalamus, adrenal and other tissues have also been discovered. Here we discuss recent advances in the understanding of autocrine/paracrine actions of BMPs in the systemic regulation of endocrine function.