This project deals with factors and mechanisms involved in regulating the growth and development of ovarian follicles. This novel intraovarian growth factor is a member of the TGF-beta superfamily. Within the ovary GDF-9 is produced exclusively by oocytes and has been shown to be essential for follicles to grow beyond the primary follicle stage. Molecular biology techniques are being used to produce recombinant GDF-9 so that intraovarian binding sites and mechanisms of action can be identified. Most of this early embryonic wastage is due to insufficient secretion of progesterone.
Progesterone is required for normal pregnancy in all mammalian species.
Therefore, studies in our laboratory are focused upon the molecular mechanisms which control the synthesis and secretion of progesterone. After years of investigation, it appears that the step in the progesterone biosynthesis pathway that is both rate limiting and regulated by second messengers is the transport of the precursor for all steroidogenesis, cholesterol, from the outer to the inner mitochondrial membrane, where conversion of cholesterol to progesterone is initiated. Phosphorylation by PKA stimulates cholesterol binding and transport, while phosphorylation by PKC is proposed to inhibit both cholesterol binding and interaction of StAR with the mitochondrial membranes. Hypothetical model for the interactions of StAR, PBR and endozepine in cholesterol transport across the mitochondrial membrane. The relationship between StAR, PBR and endozepine is not clear, but they all appear to be involved in cholesterol transport.