Characterization of androgen receptors in 7,12-dimethylbenz(a)-anthracene-induced and transplantable rat mammary tumors.

Androgenreceptorshave been documentedand char acterized in the 7,12-dimethybbenz(a)anthracene-induced rat mammarytumor and in a series of transplantablerat mammary tumors, (MTW-9A, MTW-9B, and MTW-9D). In all cases specific binding of [3H]dihydrotestosterone (DHT) to tumor cytosol was saturable, and Scatchard analysisshoweda singleclassof high-affinity,bow-capac ity binding sites. Bound [3HJDHT sedimented at —75in sucrosegradientsand was completelydisplacedby cold DHT. By means of competition studies, the androgen receptor in the 7,12-dimethylbenz(a)anthracenetumor could be distinguishedfrom that for other steroid hor mones.Neitherdexamethasonenorcortlsolcompetedfor DHTbinding,indicatingthat bindingwas not to the gluco corticoid receptor or to the cortlsol-blndingglobulin of serum. Estradiol,however,was an excellentcompetitor, but because diethylstibbestroldid not compete for [3H]DHT binding, the androgen receptor could be distin guishedfromthe estrogenreceptor. Aithoughtestosteronehasbeenshownto causeregres sion of the estrogen-dependent 7,12-dimethylbenz(a)anthracene tumor, the estrogen-independentMTW-9B and MTW-9Dtumorsdid not regressfollowingandrogen therapy, and the growth of the MTW-9B was actually slightlyenhanced.This suggeststhat the pharmacologi cal effects of androgen in mediating tumor regression may require a functionalestrogen receptorand that the androgen receptor may render the tumor sensitive to the growth-promotingeffects of androgen.