title: Impact of a constitutively active luteinizing hormone receptor on testicular gene expression and postnatal Leydig cell development.
abstract: The actions of luteinizing hormone (LH) mediated through its receptor (LHR) are critical for testicular steroidogenesis and Leydig cell differentiation. We have previously characterized transgenic mice expressing a genetically engineered, constitutively active yoked hormone-receptor complex (YHR), in which a fusion protein of human chorionic gonadotropin (hCG) was covalently linked to LHR. Elevated testosterone levels were detected in male mice expressing YHR (YHR(+)) at 3 and 5 weeks of age, accompanied by decreases in testicular weight and serum levels of LH and follicle stimulating hormone (FSH). Here we report a temporal study to identify testicular genes whose expression is altered in YHR(+) mice during postnatal development. The mRNA expression levels for the steroidogenic enzymes, P450 17alpha-hydroxylase, 17beta-hydroxysteroid dehydrogenase3 and 5alpha-reductase1 were down-regulated in 3- and 5-week-old YHR(+) testis. This result coupled with an immunohistochemical analysis of Leydig cell specific proteins and quantification of Leydig cell numbers identified a decrease in adult Leydig cells in YHR(+) mice. Surprisingly, no change was detected for cytochrome P450 side-chain cleavage or steroidogenic acute regulatory protein RNA levels between WT and YHR(+) mice. In contrast, mRNA levels for insulin-like growth factor binding protein 3 were up-regulated in 3- and 5-week-old YHR(+) mice. The mRNA levels for several germ cell-specific proteins were up-regulated at 5 weeks of age in both WT and YHR(+) mice. We conclude that premature high levels of testosterone alter the expression of a select number of testicular genes and impair the differentiation of adult Leydig cells in mice.
authors.affiliation: Department of Physiology, School of Medicine, Southern Illinois University, Carbondale, IL 62901, USA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Coonce
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Rabideau
authors.forename: Stacey
authors.initials: S
authors.lastname: McGee
authors.forename: Keriayn
authors.initials: K
authors.lastname: Smith
authors.forename: Prema
authors.initials: P
authors.lastname: Narayan
mesh_terms: D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D006063:Chorionic Gonadotropin / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D007985:Leydig Cells / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046210:Microfluidic Analytical Techniques; D008954:Models, Biological; D009928:Organ Specificity / Q000235:genetics; D011974:Receptors, LH / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013737:Testis / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*
chemical_list: D006063:Chorionic Gonadotropin; D011974:Receptors, LH; D011993:Recombinant Fusion Proteins; C102587:yoked hormone receptor, recombinant