Hypogonadotropic hypogonadism in nephrotic rats: increased sensitivity to negative feedback effects of testosterone.
Pituitary-testicular function was examined in adult male rats with aminonucleoside-induced nephrotic syndrome as a model for similar disease in humans. Nephrotic rats developed androgen deficiency, as manifested by decreased prostate and seminal vesicle weights, lower serum total and free testosterone levels, and reduced testosterone release from testes incubated in vitro. Despite hypoandrogenism, the weight and histologic appearance of the testes (light microscopy) were not affected in nephrotic rats. This androgen deficiency seemed to be a consequence of decreased gonadotropin output rather than primary testicular failure, since both pituitary gonadotropin content and serum gonadotropin levels (basally and after luteinizing hormone releasing factor; LHRH) were reduced in nephrotic rats. In addition, the percentage increase in testosterone release by testes incubated in vitro after addition of exogenous gonadotropin was similar in nephrotic and control groups. However, gonadotropin output in nephrotic rats was not impaired in the absence of testis, since no reduction was seen in either post-castration serum gonadotropin levels in vivo or gonadotropin release from pituitaries incubated in vitro. This presumed inhibitory effect of the testis on gonadotropin output in nephrotic rats was confirmed directly by demonstrating an increased sensitivity to testosterone-mediated suppression of gonadotropins in castrate animals in vivo. The presence or absence of albumin also seemed to modulate the suppressive effect of testosterone on gonadotropin output from normal pituitaries incubated in vitro. We conclude that nephrotic male rats develop hypogonadotropic hypogonadism secondary to an increase in sensitivity of the pituitary to the negative feedback effects of testosterone.
D000728:Androgens / Q000172:deficiency; D000818:Animals; D002369:Castration; D005246:Feedback; D005640:Follicle Stimulating Hormone / Q000097:blood; D006065:Gonadotropins, Pituitary / Q000172:deficiency*; D007006:Hypogonadism / Q000209:etiology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009404:Nephrotic Syndrome / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D010901:Pituitary Function Tests; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000503:physiopathology; D013739:Testosterone / Q000097:blood / Q000378:metabolism / Q000502:physiology*
D000728:Androgens; D006065:Gonadotropins, Pituitary; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone