| Autor: |
Prahalada S; Merck Research Laboratories, Merck & Company, Inc., West Point, Pennsylvania 19486., Majka JA, Soper KA, Nett TM, Bagdon WJ, Peter CP, Burek JD, MacDonald JS, van Zwieten MJ |
| Jazyk: |
angličtina |
| Zdroj: |
Fundamental and applied toxicology : official journal of the Society of Toxicology [Fundam Appl Toxicol] 1994 Feb; Vol. 22 (2), pp. 211-9. |
| DOI: |
10.1006/faat.1994.1025 |
| Abstrakt: |
Finasteride is a selective inhibitor of the enzyme 5 alpha-reductase which is responsible for the conversion of testosterone (T) to dihydrotestosterone (DHT). Finasteride is indicated for the treatment of benign prostatic hyperplasia in man (approximately 0.1 mg/kg/day). The effect of long-term treatment was studied in mice given high doses (2.5, 25, and 250 mg/kg/day) of finasteride for 83 weeks. In finasteride-treated mice, increased incidences of testicular Leydig cell hyperplasia (52% compared to 24% in control group) at doses equal to or greater than 25 mg/kg/day and Leydig cell adenomas (32% compared to 0.5% in control group) at 250 mg/kg/day were observed. There were no drug-related effects on the seminiferous tubules. Since luteinizing hormone (LH) is a trophic hormone for Leydig cells, short-term studies (5 to 14 weeks) were done to investigate the relationship between Leydig cell hyperplasia and serum LH levels in finasteride-treated mice. In these studies, there was a positive correlation between the drug-related increased incidence of Leydig cell hyperplasia and a statistically significant (p < or = 0.05) increase in serum LH levels in finasteride-treated (250 mg/kg/day) mice. Furthermore, studies in castrated male mice showed that the suppression of serum LH levels by T is reversible by inhibition of conversion of T to DHT with finasteride (250 mg/kg/day), supporting the hypothesis that DHT is involved in the regulation of LH release in mice.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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