Effect of bone morphogenetic protein-7 on folliculogenesis and ovulation in the rat

We have previously established the presence of a functional bone morphogene tic protein (BMP) system in the ovary by demonstrating the expression of BM P ligands and receptors as well as novel cellular functions. Specifically, BMP-4 and BMP-7 are expressed in theca cells, and their receptors by granul osa cells. These BMPs enhanced and attenuated the stimulatory action of FSH on estradiol and progesterone production, respectively. To investigate the underlying mechanism of the differential regulation, we analyzed mRNA leve ls for key regulators in the steroid biosynthetic pathways by RNase protect ion assay. BMP-7 enhanced P450 aromatase (P450(arom)) but suppressed steroi dogenic acute regulatory protein (StAR) mRNAs induced by FSH, whereas mRNAs encoding further-downstream steroidogenic enzymes, including P450 side-cha in cleavage enzyme and 3 beta -hydroxysteroid dehydrogenase, were not signi ficantly altered. These findings suggest that BMP-7 stimulation and inhibit ion of P450(arom) and StAR mRNA expression, respectively, may play a role i n the mechanisms underlying the differential regulation of estradiol and pr ogesterone production. To establish the physiological relevance of BMP func tions, we investigated the in vivo effects of injections of recombinant BMP -7 into the ovarian bursa of rats. Ovaries treated with BMP-7 had decreased numbers of primordial follicles, yet had increased numbers of primary, pre antral, and antral follicles, suggesting that BMP-7 may act to facilitate t he transition of follicles from the primordial stage to the pool of primary , preantral, and antral follicles. In this regard, we have also found that BMP-7 caused an increase in DNA synthesis and proliferation of granulosa ce lls from small antral follicles in vitro. In contrast to the stimulatory ac tivity, BMP-7 exhibited pronounced inhibitory effects on ovulation rate and serum progesterone levels. These findings establish important new biologic al activities of BMP-7 in the context of ovarian physiology, including foll iculogenesis and ovulation.