Evaluation of androgen antagonism of estrogen effect by dihydrotestosterone.
The antagonism of estrogen effect on the immature rat uterus by dihydrotestosterone (DHT) was evaluated in vivo. One-hundred micrograms of DHT which has been shown by previous workers [4] to saturate the androgen receptor but not bind or translocate estrogen receptor was injected daily into immature rats with or without 5 micrograms of 17 beta estradiol (E2) for three consecutive days. The animals were sacrificed on the fourth day, the uteri were excised and the uterine wet weight, cytosol protein content, [3H]-leucine and [3H]-UTP incorporation into TCA-precipitable material, and cytosol and nuclear levels of estrogen and progesterone receptors were measured. When DHT was given in conjunction with estradiol, estrogen induced uterine growth as measured by increases in uterine weight, cytosol protein content, and [3H]-leucine incorporation was significantly reduced. However, cytosol and nuclear concentrations of estrogen receptors and cytosol progesterone receptor concentration were not significantly affected, whereas progesterone treatment significantly reduced estrogen and progesterone receptor concentrations in both the cytosol and the nucleus. DHT administration did not change the binding affinity of the estrogen receptor populations and the ratio between the higher (Kd = 10(-10) M) and lower (Kd = 10(-9) M) affinity components of estrogen receptor remained unchanged. DHT treatment was also shown to significantly reduce estrogen-induced [3H]-UTP incorporation. These findings suggest that the mechanism of DHT antagonism of estrogen effect in this organ system does not involve inhibition of synthesis of estrogen receptor as has been shown for progesterone, but appears to occur by decreasing estrogen-induced RNA transcription at a point subsequent to estrogen receptor binding.
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000096:biosynthesis; D013196:Dihydrotestosterone / Q000494:pharmacology; D004965:Estrogen Antagonists; D005260:Female; D014176:Protein Biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
D000728:Androgens; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013196:Dihydrotestosterone; D012321:DNA-Directed RNA Polymerases