Disturbance or relatively important actions of antihypertensives, antifungal agent and opiate antagonist to the testicular steroidogenesis in rat.
Some of antihypertensives, opiate antagonist and antifungal agent can interfere with sexual function in both men and women. Drug-related effects on sexual function may be difficult to distinguish from the direct action of gonadal function. Clinically well known those agents to have sexual dysfunction were selected and examined the direct effect on rat's testicular steroidogenesis in vitro. Donryu rats were decapitated at 11 weeks old and isolated testes were decapsulated and preincubated with Krebs-Ringer-phosphate buffer (KRP) added with 1 micrograms/flask of LH for 60 min at 37 degrees C. Then, incubation was made with prazosin (1 micrograms), clonidine (5 micrograms), verapamil (10 micrograms), naloxone (5 micrograms) and ketoconazole (150 micrograms), 37 degrees C for 180 min in fresh KRP-buffer, respectively. Steroids were analysed with RIA, and microfluorometry after purification with quantitative thin layer chromatography. Prazosin had a tendency to produce dihydrotestosterone (DHT) indicating a facilitation of 5 alpha-reductase, and clonidine showed a significant production of estradiol (E2) with a slight production of DHT indicating a significant facilitation of aromatase. Verapamil had a action to produce significantly E2 with a slight production of DHT, and naloxone showed a significant production of both DHT and E2. Thus, these two agents showed facilitation of both 5 alpha-reductase and aromatase. Ketoconazole had a significant production of both delta 4-androstenedione (delta 4-A) and E2 while it had a significant inhibition of DHT-production, thus this had a significant production of both aromatase and C17,20-lyase while had a significant inhibitory action of 5 alpha-reductase. These findings indicates that comparatively large doses of central-nervous system depressants are one of the factors that interfere with sexual function, but it is not necessary to have direct action to testicular function, however present study revealed that some of them can cause gonadal damage and consequently progressive loss of libido.
Masubuchi
Y
Y
Department of Pharmacology, St. Marianna University School of Medicine, Kanagawa, Japan.
Akaike
M
M
Kumai
T
T
Tanaka
M
M
Watanabe
M
M
Hirai
M
M
D000735:Androstenedione / Q000378:metabolism*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism; D007654:Ketoconazole / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D013737:Testis / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D000935:Antifungal Agents; D000959:Antihypertensive Agents; D009292:Narcotic Antagonists; D009270:Naloxone; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D014700:Verapamil; D003000:Clonidine; D007654:Ketoconazole; D011224:Prazosin