REGULATION OF ESTROGEN-RECEPTOR CONCENTRATIONS IN THE RAT-BRAIN - EFFECTS OF SUSTAINED ANDROGEN AND ESTROGEN EXPOSURE

To determine whether estrogen and androgens either alone or in combina tion downregulate estrogen receptors in the brain, ovariectomized/adre nalectomized female rats received one of the following four treatments : (I) one subcutaneously placed Silastic capsule containing 10% estrad iol in cholesterol, (2) one capsule containing 10% estradiol and two c apsules containing 100% 5 alpha-dihydrotestosterone (DHT), (3) two cap sules containing DHT, or (4) empty Silastic capsules (control animals) . Animals were killed 4 or 8 days after capsule insertion and the occu pied, unoccupied and total estrogen receptor content in specific brain nuclei was determined by quantitative in vitro autoradiography. To de termine if the effects of the androgen were reversible, DHT capsules w ere removed after 4 days from half of the estradiol + DHT-treated rats , and the animals were killed 4 days later. Estradiol downregulated es trogen receptor expression in the periventricular preoptic area, media l preoptic area, bed nucleus of the stria terminalis (BNST), arcuate n ucleus (ARC), ventromedial nucleus (VMN), and medial and cortical amyg dala, decreasing receptor content by 30-41% in animals treated for 4 d ays, and by 44-60% in animals treated for 8 days with estradiol alone. DHT treatment in combination with estradiol further decreased estroge n receptor content in the BNST, ARC and VMN, relative to the estradiol -only animals. DHT in the absence of estrogen was without effect. In a nimals in which the DHT capsules were removed after 4 days of exposure , allowing the estradiol to remain for a further 4 days, estrogen rece ptor levels were indistinguishable from those measured in control anim als treated for 8 days with estradiol alone. These results demonstrate that sustained estrogen exposure downregulates levels of estrogen rec eptor in the brain and confirm that DHT synergizes with estrogen in in ducing this response in some, but not all, target neuronal groups.