Effect of FK506 on rat Leydig cell function--in vivo and in vitro study.
FK506, a macrolide antibiotic, is a potent immunosuppressant and has a biological effect similar to that of cyclosporin A (CsA). In this study, the in vivo and in vitro effects of FK506 on rat Leydig cell function were investigated. In vivo, basal testosterone levels and secretion in response to human chorionic gonadotropin (hCG) stimulation in ACl rats treated with intramuscular (IM) injections of FK506 at a dosage of 1 or 2 mg/kg/d for 14 days were not different from those of age-matched normal controls. Testicular weights (g) from rats treated with 14 injections of 1 mg/kg/d FK506 (1.08 +/- 0.08, n = 14) were similar to weights from age-matched controls (1.04 +/- 0.08, n = 14). Similarly, Wistar (Wi) rats treated with FK506 at a dosage of 1 mg/kg/d for 2 weeks showed basal testosterone and luteinizing hormone (LH) levels and secretion in response to hCG stimulation similar to those of normal controls. Histologically, the Leydig cells and germ cells in FK506-treated animals appeared normal. In vitro, basal testosterone production and response to hCG stimulation by both ACI and Wi rat Leydig cells exposed to overnight treatment of FK506 (10 to 1,000 ng/mL) were not significantly different from those of control Leydig cells. Furthermore, the viability of the Leydig cells cultured for 3 days in FK506 was not significantly different from that of controls, and they continued to secrete testosterone at a rate similar to that of controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Tai
J
J
Department of Pathology, University of British Columbia, Vancouver, Canada.
Tze
W J
WJ
Murase
N
N
Starzl
T E
TE
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D007273:Injections, Intramuscular; D007985:Leydig Cells / Q000187:drug effects*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011912:Rats, Inbred ACI; D017208:Rats, Wistar; D012016:Reference Values; D016559:Tacrolimus / Q000494:pharmacology*; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D006063:Chorionic Gonadotropin; D013739:Testosterone; D007986:Luteinizing Hormone; D016559:Tacrolimus