LH AND TESTOSTERONE MODULATE MERCURIC CHLORIDE-INDUCED ACUTE-RENAL-FAILURE IN MALE-RATS - THE IMPLICATION OF STRESS-INDUCED HYPOGONADISM

The significance of stress-induced hypogonadism remains unclear. Since plasma testosterone and LH have renotropic activity that is other tha n reproductive, we hypothesize that stress-induced hypogonadism is an adaptive response to protect the kidney. To examine this hypothesis, w e prepared hypogonadal male rats with different levels of LH and testo sterone through orchiectomy (castration), through chronic treatment wi th a slowly secreted form of gonadotropin-releasing hormone agonist (G nRH(A); GnRH(A) pretreatment), or through both treatments concomitantl y (castration with GnRH(A) pretreatment). Castrated rats had undetecta ble plasma testosterone and high plasma LH. GnRH(A)-pretreated rats ha d low plasma testosterone and normal plasma LH. Castrated rats with Gn RH(A) pretreatment had undetectable plasma testosterone and normal pla sma LH. We compared their sensitivity to HgCl2 nephrotoxicity and foun d that, when a low dose of HgCl2 (1.5 mg/kg body weight (BW)) was inje cted s.c. to induce acute renal failure, endogenous creatinine clearan ce (Ccr) decreased from 390 +/- 30 to 94 +/- 17 ml/h per kg BW in inta ct (unpretreated) rats. Such a decrease in Ccr was completely prevente d in castrated rats (388 +/- 30 ml/h per kg BW) and partially prevente d in GnRH(A)-pretreated rats (216 +/- 40 ml/h per kg BW). When a high dose of HgCl2 (2.25 mg/kg BW) was injected, half of the eight intact r ats died but castrated rats and GnRH(A)-pretreated rats survived (P<0. 05). The elevated resistance in castrated rats was reduced when plasma LH was reduced with GnRH(A) pretreatment, but was restored by additio nal pretreatment with ovine LH (40 mu g/day), as evidenced by changes in Ccr. Elevated resistance in castrated rats was also reduced by the administration of testosterone propionate. In conclusion, hypogonadism activated the preventive and defensive mechanisms that protect the ki dney through both decreased plasma testosterone and high or even norma l plasma LH.