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 than reproductive, we hypothesize that stress-induced hypogonadism is an adaptive response to protect the kidney. To examine this hypothesis, we prepared hypogonadal male rats with different levels of LH and testosterone through orchiectomy (castration), through chronic treatment with a slowly secreted form of gonadotropin-releasing hormone agonist (GnRHA; GnRHA pretreatment), or through both treatments concomitantly (castration with GnRHA pretreatment). Castrated rats had undetectable plasma testosterone and high plasma LH. GnRHA-pretreated rats had low plasma testosterone and normal plasma LH. Castrated rats with GnRHA pretreatment had undetectable plasma testosterone and normal plasma LH. We compared their sensitivity to HgCl2 nephrotoxicity and found that, when a low dose of HgCl2 (1.5 mg/kg body weight (BW)) was injected s.c. to induce acute renal failure, endogenous creatinine clearance (Ccr) decreased from 390 +/- 30 to 94 +/- 17 ml/h per kg BW in intact (unpretreated) rats. Such a decrease in Ccr was completely prevented in castrated rats (388 +/- 30 ml/h per kg BW) and partially prevented in GnRHA-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 rats died but castrated rats and GnRHA-pretreated rats survived (P < 0.05). The elevated resistance in castrated rats was reduced when plasma LH was reduced with GnRHA pretreatment, but was restored by additional pretreatment with ovine LH (40 micrograms/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 kidney through both decreased plasma testosterone and high or even normal plasma LH.
Nomura
K
K
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College, Shinjuku-ku, Japan.
Kikuchi
C
C
Ogasawara
M
M
Katayama
M
M
Ujihara
M
M
Toraya
S
S
Demura
H
H
D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D000222:Adaptation, Physiological; D000818:Animals; D003404:Creatinine / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives; D007006:Hypogonadism / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D016729:Leuprolide / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood* / Q000494:pharmacology; D008297:Male; D008627:Mercuric Chloride; D008657:Metabolic Clearance Rate; D009919:Orchiectomy; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000097:blood / Q000150:complications* / Q000378:metabolism; D013739:Testosterone / Q000097:blood* / Q000494:pharmacology
D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D008627:Mercuric Chloride; D007986:Luteinizing Hormone; D003404:Creatinine; D016729:Leuprolide