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 (PRc). 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 (ERc) and salt-extractable nuclear (ERn) oestrogen-receptor concentrations were determined by exchange assay. In all four tissues at 1 h after injection ERc fell and ERn increased, suggesting translocation of ERc into the nucleus. The extent of ERc 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 ERc was followed by a phase of replenishment, restoring ERc to preinjection values by 24 h. Concentrations of ERn in all tissues declined between 1 and 24 h, concomitant with the replenishment of ERc. Concentrations of PRc 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 PRc was seen in the amygdala. A second injection of OE2 2 h after the first injection refilled the nuclear binding sites, restoring ERn to levels indistinguishable from those seen 1 h after a single OE2 treatment. The extent of ERc depletion after two injections with OE2 was, however, proportionately less than that seen after a single treatment with OE2. The second OE2 injection raised PRc 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 PRc 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 ERc and PRc responses to oestrogen treatment. In addition, they suggest that the PRc response of the pituitary gland and POA–MBH to OE2 is influenced by previous exposure to OE2.