We compared in vivo and in vitro Leydig cell function in chronically uremic adult male rats (4 weeks after 5/ 6 nephrectomy) with that in healthy controls. Levels of serum urea nitrogen (SUN) were higher in nephrectomized animals than in controls [62 ± 6 vs. 13 ± 1 mg 5/dl (mean ± SEM), P < 0.01]; serum testosterone (T) levels were lower (135 ± 25 vs. 440 ± 64 ng 5/dl; P < 0.01). Serum LH was significantly lower in the uremic rats, being at or below the limits of detection of the assay. After in vitro exposure to various concentrations of hCG for 120 min, the mean T responses of Leydig cells from uremic rats were diminished at each dose of hCG employed (P < 0.01). Both basal levels and peak responses were reduced by approximately 50%. The apparent potency of hCG, as judged by T response, was reduced in Leydig cells from uremic rats to 3% of that in cells from normals, but showed partial recovery with increased duration of in vitro exposure to hCG, uremic cells having relative potencies of 5% (95% confidence limits, 2-12%) compared to controls at 60 min, 9% (4-19%) at 120 min, and 49% (31-72%) at 180 min. Maximum steroid responses from uremic cells remained lower at all times. The relative potency of dibutyryl cAMP after 60 min of incubation with uremic Leydig cells was 24% (9-64%) of that in controls. The number of membrane gonadotropin-binding sites per Leydig cell from uremic rats was 2900 ± 500 vs. 5700 ± 580 from controls, a reduction of 49% (P < 0.01). No significant difference in binding affinity (Ka) was found. We conclude that uremic rats have one or more defects in the sequence of events leading to Leydig cell T production. At least one of these derangements appears to be located distal to the cAMP production step. This phenomenon may be related to chronic gonadotropin understimulation or to direct effects of uremia on the Leydig cell.
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