Mark McLean, Ph.D.
Professor of Obstetrics and Gynecology, Department of Obstretrics and Gynecology
- Ph.D., Physiology and Biophysics, University of Illinois, Chicago
- M.S., Cell Biology, Northern Illinois University
Dr. McLean received his Masters degree in cell biology from Northern Illinois University and his Doctor of Philosophy in physiology and biophysics from the University of Illinois in 1986. He completed an NIH training fellowship at the University of Illinois prior to joining USF in 1990. Dr. McLean in a Professor in Obstetrics & Gynecology and Biochemistry & Molecular Biology at the USF College of Medicine where he studies the molecular regulation of the Steroidogenic Acute Regulatory Protein and the High Density Lipoprotein Receptor. He serves on several peer review committees including the National Science foundation Cell Biology Section, the National VA lipid research section, and the American Heart Association grant review panel. Dr. McLean has received research awards from the Endocrine Society, the Society for Gynecologic Investigation, and the American Heart Association.
- Regulation and expression of sterol carrier proteins
In the ovary, transport of cholesterol to the mitochondrial cytochrome P450 side-chain cleavage enzyme (P450scc) is thought to be the rate-limiting step in steroid production. Since cholesterol is insoluble m the cell, it must be transported to the P450scc via a carrier molecule which facilitates the movement of cholesterol across the mitochondrial membrane for steroid production. While the steroidogenic acute regulatory (StAR) protein is theorized to mediate cholesterol transport to the inner mitochondrial membrane, the mechanism for StAR-mediated cholesterol movement and the regulatory factors which control STAR MRNA levels in the ovary are uncertain. Gonadotropins have been shown to enhance STAR expression in NM-10 cells and a recent study by our laboratory has demonstrated that hCG stimulation increases StAR MRNA levels 8 to 9-fold in the ovary within 3 hours of treatment. These results indicate that gonadotropins increase STAR MRNA levels in parallel with an increase in progesterone production. In addition to the positive effects of gonadotropins on ovarian steroid production, altered cholesterol transport to the mitochondria has recently been identified as a key lytic event in the corpus luteum. Studies by Sandhoff and McLean suggest that one antisteroidogenic action of PGF2a is to decrease STAR MRNA levels, which results in a decline in steroid production. Based on these investigations, we hypothesize that STAR transcription is positively regulated by gonadotropins via steroidogenic factor-1, while PGF2cc working through PKC acts either indrectly, by reducing cAMP-mediated STAR gene expression, or directly, by reducing StAR expression via the negative regulatory transcription factor, DAX-1 or the Jun/Fos signal transduction pathway. This study will provide new information concerning ovarian StAR expression and function during luteal development and regression.
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