In vivo pretreatment with human chorionic gonadotropin fails to reverse the dysfunction of isolated Leydig cells from chronically uremic rats

P. D. Tsitouras, M. A. Kowatch, G. R. Briefel, J. H. Kalbfleisch, S. M. Harman, M. R. Blackman

Research output: Contribution to journalArticlepeer-review

Abstract

In order to further investigate the previously reported hypogonadal state of chronically uremic rats, we examined the effects of in vivo pretreatment with human chorionic gonadotropin (hCG) on in vivo and in vitro Leydig cell function, comparing paired intact rats with rats made chronically uremic by 5/6 nephrectomy. The in vitro testosterone (T) secretory responses to varying concentrations of hCG or dibutyryl cAMP and the number of gonadotropin receptors were determined following hemicastration. The rats were then treated with hCG for 3 days and the remaining testes were removed and studied as before. Compared with intact rats, the uremic rats had higher serum concentrations of urea nitrogen (P<0.001); serum T concentrations were lower in uremic rats before (P<0.001), but not after (P>0.6) treatment. Treatment produced increases in serum T only in uremic rats (P<0.001). Serum LH was lower in uremic rats before treatment (P<0.001) and was reduced (P<0.001) to similar levels (P>0.8) in both groups after treatment. Baseline in vitro T secretion was lower (P<0.001) from Leydig cells of uremic rats than intact rats both before and after treatment. Analysis of variance of dose-response curves showed pre- and post-treatment T secretory responses to hCG or dibutyryl cAMP in vitro to be less from Leydig cells of uremic rats (P<0.01). Before treatment, Leydig cell gonadotropin receptor number was lower in uremic than intact rats (P<0.01). Down-regulation of receptor number was observed after hCG treatment in both groups (P<0.01), but receptor number remained significantly lower on cell membranes from the uremic rats (P<0.01). The coexistent finding of reduced levels of serum luteinizing hormone and T in uremic rats and reversibility of hypoandrogenemia by in vivo hCG treatment would suggest that the hypogonadism of uremic rats is due to effects of uremia on hypothalamic-pituitary function. However, our findings that Leydig cells from chronically uremic rats exhibit marked deficits in basal and stimulated in vitro T secretion, not reversed by 3 days of in vivo gonadotropin administration, and decreased numbers of gonadotropin receptors suggest that uremia may produce one or more intrinsic derangements of Leydig cell function, independent of its effects on gonadotropin secretion.

Original languageEnglish (US)
Pages (from-to)781-789
Number of pages9
JournalBiology of reproduction
Volume33
Issue number4
DOIs
StatePublished - 1985
Externally publishedYes

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

Fingerprint

Dive into the research topics of 'In vivo pretreatment with human chorionic gonadotropin fails to reverse the dysfunction of isolated Leydig cells from chronically uremic rats'. Together they form a unique fingerprint.

Cite this