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Division of Reproductive Biology, Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205
Address all correspondence and requests for reprints to: Dr. Haolin Chen, Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205. E-mail: hchen{at}jhsph.edu.
The wealth of knowledge about the function and regulation of adult Leydig cells, the cells within the mammalian testis that produce testosterone, make these cells ideal for studying principles and mechanisms of aging. A hallmark of mammalian aging is decreased serum testosterone concentration. In the Brown Norway rat, this has been shown to be associated with the reduced ability of aged Leydig cells to produce testosterone in response to LH. Herein, we demonstrate that culturing the aged cells with dibutyryl cAMP, a membrane-permeable cAMP agonist that bypasses the LH receptor-adenlyly cyclase cascade, restores testosterone production to levels comparable to those of young cells and also restores steroidogenic acute regulatory protein and P450scc, the proteins involved in the rate-limiting steps of steroidogenesis. These results strongly suggest that signal transduction deficits are responsible for reduced steroidogenesis by aged Leydig cells and that bypassing signal transduction reverses the steroidogenic decline by the aged cells.
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  H. Chen, A. S. Pechenino, J. Liu, M. C. Beattie, T. R. Brown, and B. R. Zirkin Effect of Glutathione Depletion on Leydig Cell Steroidogenesis in Young and Old Brown Norway Rats Endocrinology, May 1, 2008; 149(5): 2612 - 2619. [Abstract] [Full Text] [PDF]
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K. Shiraishi and M. Ascoli Lutropin/Choriogonadotropin Stimulate the Proliferation of Primary Cultures of Rat Leydig Cells through a Pathway that Involves Activation of the Extracellularly Regulated Kinase 1/2 Cascade Endocrinology, July 1, 2007; 148(7): 3214 - 3225. [Abstract] [Full Text] [PDF]
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B. R. Zirkin Cyclooxygenase-2 and Reduced Steroidogenesis in the Aging Male Endocrinology, October 1, 2005; 146(10): 4200 - 4201. [Full Text] [PDF]
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 L. Luo, H. Chen, and B. R. Zirkin Temporal Relationships Among Testosterone Production, Steroidogenic Acute Regulatory Protein (StAR), and P450 Side-Chain Cleavage Enzyme (P450scc) During Leydig Cell Aging J Androl, January 1, 2005; 26(1): 25 - 31. [Abstract] [Full Text] [PDF]
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