Inhibition of Anterior Pituitary Estrogen-Receptor Complex Formation by Low-Affinity Interaction with 5 α-Dihydrotestosterone

A possible role for 5α-dihydrotestosterone in the anterior pituitary of the rat has been investigated by determining the influence of this androgen upon the binding of 17β-estradiol to its cytoplasmic receptor. Under equilibrium binding conditions, both testosterone and 5α-dihydrotestosterone are very poor competitors for the estrogen binding sites, as compared to estrogenic compounds. 5α-Dihydrotestosterone, however, inhibits the initial rate of formation of the estradiolreceptor complex in a concentration-dependent manner. Steroidal specificity of this inhibition is indicated by the failure of progesterone to elicit the same effect. The androgen inhibition appears to involve low-affinity interaction with the estrogen receptor, since no high-affinity binding of 5αdihydrotestosterone could be detected. Kinetic analysis indicated that the inhibition is competitive, involving interaction at the estrogen-binding site of the receptor.(Endocrinology97: 231, 1975)