title: Differential effects of hypothalamic IGF-I on gonadotropin releasing hormone neuronal activation during steroid-induced LH surges in young and middle-aged female rats.
abstract: Interactions between brain IGF-I receptors and estrogen receptors regulate female reproductive physiology and behavior. The present study investigated potential mechanisms by which IGF-I receptors in the neuroendocrine hypothalamus regulate GnRH neuronal activation and LH release in young and middle-aged female rats under estradiol (E2) positive feedback conditions. We infused vehicle, IGF-I, or JB-1, a selective antagonist of IGF-I receptors, into the third ventricle of ovariectomized female rats primed with E2 and progesterone or vehicle. In young females, blockade of IGF-I receptors attenuated the steroid hormone-induced LH surge, reduced the percent of GnRH neurons expressing c-fos on the day of the LH surge, and decreased the total number of neurons expressing c-fos in the preoptic area. Middle-aged females had fewer GnRH neurons expressing c-fos during the LH surge than young females, and the LH surge amplitude was attenuated. Infusion of an IGF-I dose previously shown to increase LH surge amplitude did not increase the percent of GnRH neurons expressing c-fos in middle-aged females. Brain IGF-I receptor blockade did not modify E2 induction of progestin receptor-immunoreactive neurons in the preoptic area, arcuate, or ventromedial hypothalamus of young rats. These findings indicate that brain IGF-I receptors are required for E2 activation of GnRH neurons in young rats and for robust GnRH release from axon terminals in middle-aged females. IGF-I likely exerts its effects by actions on E2-sensitive neurons that are upstream of GnRH neurons and terminals.
authors.affiliation: Department of Obstetrics/Gynecology and Women's Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Ullmann 1211, Bronx, New York 10461, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Brigitte J
authors.initials: BJ
authors.lastname: Todd
authors.forename: Kimberly
authors.initials: K
authors.lastname: Thornton
authors.forename: Anne M
authors.initials: AM
authors.lastname: Etgen
authors.forename: Genevieve
authors.initials: G
authors.lastname: Neal-Perry
mesh_terms: D000367:Age Factors; D000818:Animals; D002452:Cell Count; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000097:blood*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D011980:Receptors, Progesterone; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone; D017526:Receptor, IGF Type 1