Regulation of pulsatile luteinizing hormone secretion in experimental uremia

Previous studies have shown that male rats with experimental uremia manifest profound suppression of circulating LH and testosterone levels, yet, paradoxically, after castration gonadotropin levels are elevated greatly above those of nonuremic castrate control rats. To investigate further this phenomenon, we characterized pulsatile LH secretion in experimental uremia. Mature orchidectomized male Wistar rats with subtotal nephrectomy demonstrated a 43% reduction of LH pulse frequency, but a 157% increase in pulse amplitude and a 335% increase in mean LH levels compared with sham-operated controls. All pulse parameters were highly correlated with plasma creatinine (r = 0.53-0.75). To determine the mechanism of the increased pulse amplitude, we tested responsiveness of the postcastration uremic pituitary to exogenous GnRH (0.01-10 micrograms/kg) in a Latin square design. Plasma LH response was linearly related to the logarithm of the GnRH dose in uremic and control rats, but was markedly increased in uremic rats. We conclude that the uremia causes decreased LH pulse frequency independent of testicular feedback. Pituitary hypersensitivity to GnRH magnifies LH pulse amplitude and thereby is the major factor causing the paradoxical LH hyperelevation after castration.