A characterization of estrogen's influence on anterior pituitary androgen receptor: Effect of bromocriptine treatment

The action of gonadal steroids are mediated through the binding to specific intracellular receptors. Our recent studies have demonstrated that estrogen (E) treatment will increase the concentration of cytosolic androgen receptor (AR) in the anterior pituitary (AP) gland perhaps reflecting in increased sensitivity of this tissue circulating androgen. However, chronic E treatment also increases AP weight and cell number. Consequently, the following studies were performed to determine the relationship between increases in AP cytosolic AR and increases in AP weight following chronic E treatment. Gonadectomized male and female Fischer 344 (F344) rats were implanted with a 5-mm Silastic capsule of 17β-estradiol. Control animals were sham implanted. Animals were sacrificed at 1, 3, 7 and 21 days after the commencement of E treatment and AP glands were weighed and processed for cytosolic AR and nuclear estrogen receptor (ER) content. AR and ER were determined by in vitro binding assays using ³H-dihydrotestosterone and ³H-estradiol, respectively. AP weight increased significantly by 3 days of E treatment in females and by 7 days in males (p < 0.05). However, AP weight of E-treated males was significantly less than females throughout (p < 0.05). Significant increases in AP cytosolic AR content (fmol bound/gland) were detected within 1 day of E treatment to female rats but not until 7 days in male rats. AP cytosolic AR content peaked at 7 days of E treatment in females and 21 days in males. AP cytosolic AR concentration (expressed as per milligram cytosol protein) peaked 3 days after E at which time there were significant E effects in both males and females. AR concentration was not elevated following 21 days of E treatment to female rats. These data suggested that the increases in AP weight following 21 days of E treatment were masking the effects of E on AP cytosolic AR when expressed on a per milligram protein basis. Consequently, we inhibited E-induced AP growth by the simultaneous administration of bromocriptine (BR). BR was administered concurrently with E to female F344 rats by the implantation of a constant release pellet of BR (25 mg/animal/21 days). Animals were sacrificed 21 days following E treatment. Concurrent BR treatment significantly reduced AP weight and plasma prolactin levels following E treatment and increased the concentration but not the content of AR (p < 0.05). These data demonstrate that increases in AR number in the AP as a result of E exposure is not a consequence of AP growth. This suggests that E-induced increases in AR are not related to lactotroph proliferation.