title: Ovariectomy-induced increases in hypothalamic serotonin-1A receptor function in rats are prevented by estradiol.
abstract: The present study investigated the effects of long-term estradiol withdrawal (ovariectomy) on hypothalamic serotonin-1A (5-HT(1A)) receptor signaling. Changes in neuroendocrine responses to the 5-HT(1A) agonist 8-OH-DPAT and levels of G(z) protein in the hypothalamus were used to examine 5-HT(1A) receptor signaling. Five days following ovariectomy, rats received daily injections of either 2 microg of beta-estradiol 3-benzoate or vehicle (subcutaneously) for 2, 4 or 14 days. Twenty-four hours after the last injection, and 15 min prior to sacrifice, rats were injected with (+/-)8-OH-DPAT (50 micro;g/kg, s.c.) or saline. Estradiol treatment did not alter basal corticotropin (ACTH) or oxytocin levels. Injection of (+/-)8-OH-DPAT produced significant increases in plasma ACTH and oxytocin levels. In the vehicle-treated rats, hormone responses to 8-OH-DPAT were enhanced in rats that received injections for 14 days compared with rats that received injections for either 2 or 4 days. Estradiol treatment for 4 or 14 days blunted this enhanced ACTH response to 8-OH-DPAT, whereas the oxytocin response to 8-OH-DPAT was only blunted after 14 daily injections of beta-estradiol 3-benzoate. The treatment with beta-estradiol 3-benzoate (2 microg/rat) did not reduce membrane-associated G(z) protein levels in the paraventricular nucleus of the hypothalamus. Hence, the inhibitory influence of a low dose of beta-estradiol 3-benzoate on 5-HT(1A) receptor signaling in the hypothalamus is not accompanied by a change in the levels of G(z) protein in the paraventricular hypothalamic nucleus. Results from the present study indicate a supersensitivity of 5-HT(1A) receptors after withdrawal of estradiol and suggest that estradiol suppresses 5-HT(1A) receptor signaling.
authors.affiliation: Center for Serotonin Disorders Research, Stritch School of Medicine, Loyola University Chicago, Maywood, Ill., USA.
authors.forename: Dani K
authors.initials: DK
authors.lastname: Raap
authors.forename: Lydia L
authors.initials: LL
authors.lastname: DonCarlos
authors.forename: Francisca
authors.initials: F
authors.lastname: Garcia
authors.forename: Yahong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Muma
authors.forename: George
authors.initials: G
authors.lastname: Battaglia
authors.forename: Louis D
authors.initials: LD
authors.lastname: Van de Kar
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects; D000818:Animals; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D015151:Immunoblotting; D010052:Ovariectomy; D010121:Oxytocin / Q000097:blood / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; C074283:estradiol 3-benzoate; D004958:Estradiol; D010121:Oxytocin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000324:Adrenocorticotropic Hormone; D019204:GTP-Binding Proteins