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.