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Publication : Failure of normal adult Leydig cell development in androgen-receptor-deficient mice.

First Author  O'Shaughnessy PJ Year  2002
Journal  J Cell Sci Volume  115
Issue  Pt 17 Pages  3491-6
PubMed ID  12154079 Mgi Jnum  J:78785
Mgi Id  MGI:2386152 Doi  10.1242/jcs.115.17.3491
Citation  O'Shaughnessy PJ, et al. (2002) Failure of normal adult Leydig cell development in androgen-receptor-deficient mice. J Cell Sci 115(Pt 17):3491-6
abstractText  During testicular development, fetal and adult populations of Leydig cells arise sequentially. Previous studies have shown that androgen action is required for normal steroidogenic activity in the mouse testis. Therefore, to determine the role of androgens in regulating fetal and adult Leydig cell differentiation and function, Leydig development has been measured in mice lacking functional androgen receptors (AR-null). The Leydig cell number was normal on day 5 after birth in AR-null mice but failed to increase normally thereafter and was about 30% of the control level on day 20 and about 60% of control level in adult animals. Levels of 15 different mRNA species expressed specifically in Leydig cells were measured by real-time PCR in AR-null and control animals. Expression levels of all mRNA species were normal on day 5 when only fetal Leydig cells are present. In older animals, which contain predominantly adult Leydig cells, five of the mRNA species (3beta-hydroxysteroid dehydrogenase (3betaHSD) type 1, cytochrome P450scc, renin, StAR protein and luteinising hormone receptor) were expressed at normal or increased levels in AR-null mice. All other mRNA species measured showed significantly reduced expression in older animals, and three of these mRNA species (17beta-hydroxysteroid dehydrogenase type III, prostaglandin D (PGD)-synthetase and 3betaHSD type VI), which are only expressed in the adult population of Leydig cells, were barely detectable in the adult AR-null mouse. The results show that in the absence of androgen receptors, fetal Leydig cell function is normal, but there is a developmental failure of adult Leydig cell maturation, with cells only aquiring partial characteristics of the adult population.
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