Testicular function in experimental uremia.

A model for the study of testicular function in experimental uremia induced by subtotal nephrectomy in mature male rats is described. Glomerular filtration rate was reduced by 87%, resulting in stable uremia for up to 13 weeks with characteristic biochemical changes and reduction in weight of testes, prostate, seminal vesicles, and epididymis but not of heart, liver, spleen, or epididymal fat-pads in comparison with pair-fed and sham-operated, ad libitum-fed littermate controls. Basal serum LH, FSH, and testosterone were reduced and PRL levels increased in chronic uremic rats compared with pair-fed and sham-operated controls. Intratesticular and peripheral venous testosterone levels were reduced by 73-85%, whereas spermatic vein testosterone levels were reduced by 47% suggesting a reduction in blood flow to the uremic rat testis. Sensitivity of uremic Leydig cells to human CG stimulation was normal to increased both in vivo and in vitro without changes in LH receptor affinity or numbers. Fertility was markedly impaired in uremic rats but was restored to normal by either human CG or testosterone treatment. Spermatogenesis was minimally depressed after up to 3 months of uremia. These studies suggest that this experimental paradigm is a suitable model for studying the pathogenesis of early changes in uremic hypogonadism. The predominant early changes of uremic hypogonadism are due to central defects in regulation of pituitary LH secretion with consequent testicular and peripheral hypoandrogenism but initial preservation of spermatogenesis.