Impact of a constitutively active luteinizing hormone receptor on testicular gene expression and postnatal Leydig cell development

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:298

Article

Coonce, Mary M.¹  Rabideau, Amanda C.¹  McGee, Stacey¹  Smith, Keriayn²  Narayan, Prema¹ 

[1] So Illinois Univ, Dept Physiol, Sch Med, Carbondale, IL 62901 USA

[2] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA

关键词: Luteinizing hormone receptor;    Constitutive activation;    Gene expression;    Leydig cell development;   

DOI  :  10.1016/j.mce.2008.10.016

来源: Elsevier

【 摘 要 】

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 17 alpha-hydroxylase,17 beta-hydroxysteroid dehydrogenase3 and 5 alpha-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. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

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