Effect of estrogen on androgen receptor dynamics in female rat pituitary

We examined the role of estrogen in regulating the number of androgen receptors (AR) in the pituitary gland of the female rat. Female Sprague-Dawley rats (240-280 g) that were ovariectomized for 3 days were used in this study. AR numbers were determined in pituitary cytosol and nuclear fractions by binding and exchange assays using the synthetic ligand 17 alpha-methyl-3H-trienolone. The administration of a single dose of estradiol benzoate [(EB) 10 micrograms/100 g BW] to ovariectomized female rats resulted in a 60% increase in cytosolic AR which was significantly (P less than 0.01) elevated above that of oil-treated controls by 12 h post EB. Cytosolic AR levels remained elevated for as long as 48 h post EB (213% of controls). Saturation analysis of pituitary cytosolic AR revealed a single, high affinity binding site for 17 alpha-methyl-3H-trienolone exhibiting an apparent dissociation constant (Kd) of 0.5 X 10(-10) M in both EB- and oil-treated animals. The administration of cycloheximide (1 mg/kg BW) before EB administration prevented the EB-induced rise in AR when measured 8 h post EB. When dihydrotestosterone (1.5 mg) was injected 24 h after EB or oil, there was a rapid increase in nuclear AR accompanied by a rapid decrease in cytosolic AR. The increase in nuclear AR was significantly greater (P less than 0.05) in EB-pretreated animals vs. oil-treated controls. These observations show that a potential synergism exists between androgen and estrogen in the female rat pituitary and suggest that androgens may play an important role in regulating cyclic pituitary hormone release.