Reversibility of cyclosporine-induced hypoandrogenism in rats.
In an attempt to determine whether the inhibition of the hypothalamic-pituitary-testicular axis induced by oral cyclosporine (CsA) is reversible, intact adult male rats were treated with 30 mg/kg oral CsA daily for 4 weeks, and then vehicle (orange juice) for the next 4 weeks. A second group of animals (control) was fed orange juice throughout the entire 8 weeks of the experiment. Serum testosterone (T) was decreased significantly (P less than 0.01) after 4 weeks of CsA treatment when compared with controls. After cessation of oral CsA for the next 4 weeks, there was no difference in serum T between the control and CsA-treated groups. Serum LH, intratesticular T, ventral prostate (VP) and seminal vesicle (SV) weights paralleled the serum T levels at 4 and 8 weeks--i.e., all values were decreased in the 4-week CsA-treated group when compared with controls, and these returned to normal at 8 weeks. Intratesticular 17 alpha-hydroxylase and 17,20-desmolase activities were significantly lower after 4 weeks of CsA treatment; following cessation of the CsA, these enzymatic values returned to normal within 4 weeks. These data demonstrate that at the duration of treatment and the dose studied, the CsA-induced inhibition of the hypothalamic-pituitary-testicular axis of the intact adult rat is completely reversible.
Sikka
S C
SC
Department of Surgery, UCLA School of Medicine, Torrance, CA 90509.
Koyle
M A
MA
Swerdloff
R S
RS
Rajfer
J
J
D000728:Androgens / Q000172:deficiency*; D000818:Animals; D003404:Creatinine / Q000097:blood; D003524:Cyclosporins / Q000097:blood / Q000633:toxicity*; D007006:Hypogonadism / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000201:enzymology; D013739:Testosterone / Q000097:blood
D000728:Androgens; D003524:Cyclosporins; D013739:Testosterone; D003404:Creatinine