Antiandrogens do not reverse androgen-induced inhibition of sex hormone-binding globulin levels in adult female rhesus monkeys.
Studies were done to determine if changes in plasma sex hormone-binding globulin (SHBG) levels could serve as a specific marker of androgenic and antiandrogenic activities in rhesus monkeys. Treatment of adult female monkeys for 11 days with 17 alpha-methyltestosterone (MeT) produced dose and time-dependent reductions in SHBG levels. However, the non-steroidal antiandrogen flutamide (80 mg/monkey.day) did not inhibit the reduction in SHBG levels when coadministered with MeT, nor did it have an effect on SHBG levels when given alone. In contrast, the steroidal antiandrogens Win 49596 (100 mg/monkey.day) and cyproterone acetate (80 mg/monkey.day) significantly (P less than 0.01) reduced SHBG plasma concentration to about 50% of pretreatment control values whether given alone or in combination with MeT. Furthermore, Win 49596 reduced SHBG levels at doses as low as 4 mg/monkey, whereas cortico-steroid-binding globulin levels were not affected. In ovariectomized monkeys, MeT treatment (4 mg/monkey.day for 15 days) reduced plasma SHBG levels to 42% of pretreatment values and delayed the onset of withdrawal menstrual bleeding compared to that in controls. When administered concurrently with MeT, flutamide (100 mg/monkey.day) antagonized the effect on withdrawal bleeding, but was without effect on SHBG levels. Therefore, plasma SHBG levels cannot be used as a specific indicator of androgenic or antiandrogenic activity and may not be regulated through the classical androgen receptor.
Winneker
R C
RC
Department of Pharmacology, Sterling Research Group, Rensselaer, New York 12144.
Wagner
M M
MM
Shaw
C J
CJ
Snyder
B W
BW
D000726:Androgen Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000728:Androgens / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D003534:Cyproterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017373:Cyproterone Acetate; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D008251:Macaca / Q000097:blood*; D008253:Macaca mulatta / Q000097:blood*; D008777:Methyltestosterone / Q000494:pharmacology; D010052:Ovariectomy; D011278:Pregnanes / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*
D000726:Androgen Antagonists; D000728:Androgens; D015415:Biomarkers; D011278:Pregnanes; D011720:Pyrazoles; D012738:Sex Hormone-Binding Globulin; D017373:Cyproterone Acetate; D005485:Flutamide; D003534:Cyproterone; D008777:Methyltestosterone; C060492:zanoterone