PMID- 12154079 OWN - NLM STAT- MEDLINE DCOM- 20030416 LR - 20220215 IS - 0021-9533 (Print) IS - 0021-9533 (Linking) VI - 115 IP - Pt 17 DP - 2002 Sep 1 TI - Failure of normal adult Leydig cell development in androgen-receptor-deficient mice. PG - 3491-6 AB - 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. FAU - O'Shaughnessy, Peter J AU - O'Shaughnessy PJ AD - Institute of Comparative Medicine, University of Glasgow Veterinary School, Bearsden Rd, Glasgow G61 1QH, UK. p.j.o'shaughnessy@vet.gla.ac.uk FAU - Johnston, Heather AU - Johnston H FAU - Willerton, Louise AU - Willerton L FAU - Baker, Paul J AU - Baker PJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Cell Sci JT - Journal of cell science JID - 0052457 RN - 0 (RNA, Messenger) RN - 0 (Receptors, Androgen) RN - EC 1.3.99.5 (3-Oxo-5-alpha-Steroid 4-Dehydrogenase) SB - IM MH - 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/metabolism MH - Animals MH - Gene Expression Regulation, Developmental MH - Leydig Cells/cytology/*physiology MH - Male MH - Mice MH - Mice, Inbred Strains MH - Mice, Knockout MH - RNA, Messenger/metabolism MH - Receptors, Androgen/genetics/*metabolism MH - Testis/chemistry/cytology/pathology/physiology EDAT- 2002/08/03 10:00 MHDA- 2003/04/17 05:00 CRDT- 2002/08/03 10:00 PHST- 2002/08/03 10:00 [pubmed] PHST- 2003/04/17 05:00 [medline] PHST- 2002/08/03 10:00 [entrez] AID - 10.1242/jcs.115.17.3491 [doi] PST - ppublish SO - J Cell Sci. 2002 Sep 1;115(Pt 17):3491-6. doi: 10.1242/jcs.115.17.3491.