Oestrogen induction of progestin receptors in the rat brain and pituitary gland: quantitative and kinetic aspects

Abstract

The processes of oestrogen-receptor binding, translocation and nuclear processing in the pituitary gland, preoptic area (POA), mediobasal hypothalamus (MBH) and amygdala were explored in relation to the induction of cytosol progestin receptors (PR_c). Ovariectomized rats were injected i.v. with a single saturating dose (3·6 μg/kg body wt) of oestradiol-17β (OE₂). At various times thereafter cytosol (ER_c) and salt-extractable nuclear (ER_n) oestrogen-receptor concentrations were determined by exchange assay. In all four tissues at 1 h after injection ER_c fell and ER_n increased, suggesting translocation of ER_c into the nucleus. The extent of ER_c depletion, however, was not identical in all tissues: substantially less depletion was observed in the amygdala (34%) and POA–MBH (56%) than in the pituitary gland (74%). Depletion of ER_c was followed by a phase of replenishment, restoring ER_c to preinjection values by 24 h. Concentrations of ER_n in all tissues declined between 1 and 24 h, concomitant with the replenishment of ER_c. Concentrations of PR_c in the pituitary gland and POA–MBH increased during the first 12 h after injection of OE₂ to a plateau value between 12 and 24 h, then declined to control values by 72 h. No induction of PR_c was seen in the amygdala. A second injection of OE₂ 2 h after the first injection refilled the nuclear binding sites, restoring ER_n to levels indistinguishable from those seen 1 h after a single OE₂ treatment. The extent of ER_c depletion after two injections with OE₂ was, however, proportionately less than that seen after a single treatment with OE₂. The second OE₂ injection raised PR_c concentrations above those seen after a single injection in the POA–MBH but not in the pituitary gland. When the two OE₂ injections were more widely spaced (14 h apart) the PR_c response in both the pituitary gland and POA–MBH was greater than after a single OE₂ injection, and was comparable to that seen in animals given a very large dose (360 μg/kg body wt) of OE₂. These results confirm the existence of differences between the pituitary gland, POA–MBH and amygdala in the ER_c and PR_c responses to oestrogen treatment. In addition, they suggest that the PR_c response of the pituitary gland and POA–MBH to OE₂ is influenced by previous exposure to OE₂.