The effect of a 5 alpha-reductase inhibitor on androgen physiology in the immature male rat.
To provide insight into the role of 5 alpha-dihydrotestosterone (DHT) in postnatal androgen physiology, we administered the 5 alpha-reductase inhibitor finasteride to male rats from birth through the onset of puberty. In 4-week-old control rats serum testosterone levels averaged 0.21 ng/ml, and DHT levels averaged 0.64 ng/ml. By 7 weeks of age, testosterone levels increased more than 7-fold to 1.57 ng/ml, while the circulating DHT level declined to 0.26 ng/ml. In both the 4- and 7-week-old inhibitor-treated animals, circulating DHT levels were 25-50% of control values, and circulating testosterone levels were higher than control values. In 7-week-old inhibitor-treated rats, the weights of prostate, penis, seminal vesicles, and epididymal tissues were only 30-50% those of the controls. However, DHT formation is apparently not critical for postnatal development of the preputial glands or the androgen-dependent perineal muscles, since the weights of these tissues were not affected by treatment with inhibitor. Treatment with the 5 alpha-reductase inhibitor had no apparent effect on testicular histology or daily sperm production despite the fact that testicular DHT content was lower (70%) and testosterone content was higher (250%) than those in controls. We conclude that DHT formation is important for the normal postnatal growth of the prostate, seminal vesicles, epididymis, and penis and may be important for normal feedback control of testosterone production in rats, but that its formation is not critical for the onset of spermatogenesis or the development of the preputial glands or the androgen-dependent perineal muscles.
George
F W
FW
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas 75235.
Johnson
L
L
Wilson
J D
JD
D058891:5-alpha Reductase Inhibitors; D000736:Androstenes / Q000494:pharmacology*; D000818:Animals; D001378:Azasteroids / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000097:blood*; D018120:Finasteride; D008297:Male; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012741:Sexual Maturation / Q000187:drug effects*; D013091:Spermatogenesis / Q000187:drug effects; D013260:Steroids, Heterocyclic / Q000494:pharmacology*; D013737:Testis / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D013739:Testosterone / Q000097:blood / Q000378:metabolism*
D058891:5-alpha Reductase Inhibitors; D000736:Androstenes; D001378:Azasteroids; D013260:Steroids, Heterocyclic; D013196:Dihydrotestosterone; D013739:Testosterone; D018120:Finasteride