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Laboratory of Mammalian Reproductive Biology and Genomics (Y.K., Q.L., G.W.S.), Departments of Animal Science (Y.K., F.J.-K., Q.L., J.Y., R.H., J.J.I., P.M.C., G.W.S.) and Physiology (J.Y., J.J.I., G.W.S.), and Center for Animal Functional Genomics (J.Y., J.J.I., P.M.C., G.W.S.), Michigan State University, East Lansing, Michigan 48824
Address all correspondence and requests for reprints to: Dr. George W. Smith, Department of Animal Science, Michigan State University, 1230 Anthony Hall, East Lansing, Michigan 48824. E-mail: smithge7{at}msu.edu.
We recently obtained evidence that cocaine- and amphetamine-regulated transcript (CART), a potent anorectic neuropeptide, is expressed in the bovine ovary. The objectives of this study were to characterize bovine ovarian CART and determine its localization, regulation, and regulatory role during follicular development. CART mRNA was detected in stroma of adult ovaries and in large follicles, but was undetectable in several peripheral tissues, fetal ovaries, and corpora lutea. Within the ovary, CART mRNA and peptide were localized to the granulosal layer of some, but not all, antral follicles, with low, but detectable, expression in oocytes and cumulus cells. CART mRNA was undetectable in granulosal cells of dominant ovulatory follicles collected before and after the preovulatory gonadotropin surge, but was detected in the granulosal layer of adjacent subordinate follicles. In addition, amounts of CART mRNA and follicular fluid concentrations of CART peptide were greater in subordinate follicles vs. dominant follicles of the first follicular wave. Furthermore, CART treatment inhibited basal estradiol production, but not progesterone production, by granulosal cells in a dose-dependent fashion, and the effect was dependent on stage of cell differentiation. We conclude that granulosal cell CART expression is temporally regulated and potentially associated with follicle health status, and CART can inhibit granulosal cell estradiol production. Thus, CART may be a novel local regulator of follicular atresia in the bovine ovary.
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  L. Lv, F. Jimenez-Krassel, A. Sen, A. Bettegowda, M. Mondal, J. K. Folger, K.-B. Lee, J. J. Ireland, and G. W. Smith Evidence Supporting a Role for Cocaine- and Amphetamine-Regulated Transcript (CARTPT) in Control of Granulosa Cell Estradiol Production Associated with Dominant Follicle Selection in Cattle Biol Reprod, September 1, 2009; 81(3): 580 - 586. [Abstract] [Full Text] [PDF]
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J.J. Ireland, A.E. Zielak-Steciwko, F. Jimenez-Krassel, J. Folger, A. Bettegowda, D. Scheetz, S. Walsh, F. Mossa, P.G. Knight, G.W. Smith, et al. Variation in the Ovarian Reserve Is Linked to Alterations in Intrafollicular Estradiol Production and Ovarian Biomarkers of Follicular Differentiation and Oocyte Quality in Cattle Biol Reprod, May 1, 2009; 80(5): 954 - 964. [Abstract] [Full Text] [PDF]
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 A. Sen, L. Lv, N. Bello, J. J. Ireland, and G. W. Smith Cocaine- and Amphetamine-Regulated Transcript Accelerates Termination of Follicle-Stimulating Hormone-Induced Extracellularly Regulated Kinase 1/2 and Akt Activation by Regulating the Expression and Degradation of Specific Mitogen-Activated Protein Kinase Phosphatases in Bovine Granulosa Cells Mol. Endocrinol., December 1, 2008; 22(12): 2655 - 2676. [Abstract] [Full Text] [PDF]
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 A. Sen, A. Bettegowda, F. Jimenez-Krassel, J. J. Ireland, and G. W. Smith Cocaine- and Amphetamine-Regulated Transcript Regulation of Follicle-Stimulating Hormone Signal Transduction in Bovine Granulosa Cells Endocrinology, September 1, 2007; 148(9): 4400 - 4410. [Abstract] [Full Text] [PDF]
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