Androgen control of cytosol progesterone receptor levels in the MT-W9B transplantable mammary tumor in the rat.
The effect of androgen on the levels of the cytosol progesterone receptor was examined in the transplantable rat mammary tumor MT-W9B and in the normal uteri of inbred WF rats. Progesterone receptor levels were barely detectable in tumors grown in male WF rats but were increased after castration or administration of 17 beta-estradiol. Both effects were blocked by testosterone. In tumors grown in intact female rats, both testosterone and dihydrotestosterone decreased progesterone receptor levels in a dose-dependent manner, and testosterone completely blocked the estradiol-induced increase in progesterone receptor levels in tumors from ovariectomized rats. The inhibitory effect of testosterone in female rats was blocked by the antiandrogen flutamide, suggesting an androgen receptor-dependent mechanism. Neither dihydrotestosterone nor testosterone had any effect on basal levels of progesterone receptor in tumors from ovariectomized rats. In uterus, up to 5 mg dihydrotestosterone/kg did not affect progesterone receptor levels, and a dose of 5 mg/kg was also uterotropic. This fact plus the finding that testosterone only partially blocked the estradiol-induced increase in uterine progesterone receptor levels suggested stimulation of different cell types by testosterone and estradiol. This did not appear to be the case in the tumor, however. Androgen is suggested to act as a negative modulator of progesterone receptor levels, which might have clinical relevance in terms of hormone therapy of breast cancer.
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002369:Castration; D003600:Cytosol / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000032:analysis / Q000378:metabolism*; D009368:Neoplasm Transplantation; D051381:Rats; D011920:Rats, Inbred WF; D011980:Receptors, Progesterone / Q000032:analysis / Q000378:metabolism*; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology; D014599:Uterus / Q000032:analysis / Q000378:metabolism
D000728:Androgens; D011980:Receptors, Progesterone; D013196:Dihydrotestosterone; D013739:Testosterone; D004958:Estradiol; D005485:Flutamide