Inhibition of anterior pituitary estrogen-receptor complex formation by low-affinity interaction with 5...

A possible role for 5alpha-dihydrotestosterone in the anterior pituitary of the rat has been investigated by determining the influence of this androgen upon the binding 17beta-estrasiol to its cytoplasmic receptor. Under equilibrium binding conditions, both testosterone and 5 alpha-dihydrotestosterone are very poor competitors for the estrogen binding sites, as compared to estrogenic compounds. 5alpha-Dihydrotestosterone, however, inhibits the initial rate of formation of the estradiol-receptor complex in a concentration-dependent manner. Steroidal specificity of this incubation 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 5alpha-dihydrotestosterone could be detected. Kinetic analysis indicated that the inhibition is competitive, involving interaction at the estrogen-binding site of the receptor.