title: Comparison of age- and sex-related changes in cell nuclear estrogen-binding capacity and progestin receptor induction in the rat brain.
abstract: Previous studies have suggested parallels between the mechanisms underlying sexual differentiation and age-related loss of reproductive cyclicity in the female rat. Both appear to involve the actions of estrogen on the brain and are associated with a reduction in hypothalamic estrogen sensitivity. In this study the effects of sex and aging on cell nuclear estrogen receptor-binding capacity and cytosol progestin receptor induction in the pituitary gland, periventricular preoptic area (PVP), medial preoptic area (mPO), bed nucleus of the stria terminalis, arcuate median eminence region (ARC), ventromedial nucleus (VMN), and corticomedial amygdala were directly compared. Young (2.5 months old) and middle-aged (8-10 months old) male and female and old (19 months old) female rats were gonadectomized 14 days before adrenalectomy (ADX). For comparison of cell nuclear estrogen receptor-binding capacity, animals received a saturating dose of estradiol (36.0 micrograms/kg BW) 3 days after ADX and 1 h before death. Cell nuclear estrogen binding was measured by an in vitro exchange assay. For comparison of estrogen-induced progestin receptors, animals received a sc placed Silastic capsule containing 10% 17 beta-estradiol at the time of ADX and were killed 3 days later. Cytosol progestin binding was measured by an in vitro binding assay. Cell nuclear estrogen-binding capacities and cytosol progestin receptor induction were lower in the PVP, mPO, and VMN of the young male than in the young female. In the female, the level of progestin receptor induction in the pituitary and brain was unaffected by age; however, cell nuclear estrogen-binding capacity in the mPO, VMN, ARC, and pituitary gland was lower in old than in middle-aged females. These results demonstrate that the effects of sexual differentiation and aging on the hypothalamus involve similar, but not identical, region-specific reductions in cell nuclear estrogen receptor-binding capacity. The consequences of these reduced estrogen receptor binding levels in terms of the induction of progestin receptor in response to estrogen exposure are, however, very different in the male compared to those in old female rats.
authors.affiliation: Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: T J
authors.initials: TJ
authors.lastname: Brown
authors.forename: N J
authors.initials: NJ
authors.lastname: MacLusky
authors.forename: M
authors.initials: M
authors.lastname: Shanabrough
authors.forename: F
authors.initials: F
authors.lastname: Naftolin
mesh_terms: D000315:Adrenalectomy; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D002467:Cell Nucleus / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D008297:Male; D009919:Orchiectomy; D010052:Ovariectomy; D010902:Pituitary Gland / Q000254:growth & development / Q000378:metabolism; D011301:Preoptic Area / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012727:Sex Characteristics; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004958:Estradiol