Differential effects of hypothalamic IGF-I on gonadotropin releasing hormone neuronal activation during steroid-induced LH surges in young and middle-aged female rats

Yan Sun, Brigitte J. Todd, Kimberly Thornton, Anne M. Etgen, Genevieve Neal-Perry

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 Gn RH neurons in young rats and for robustGnRHrelease 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.

Original languageEnglish (US)
Pages (from-to)4276-4287
Number of pages12
JournalEndocrinology
Volume152
Issue number11
DOIs
StatePublished - Nov 2011

Fingerprint

Insulin-Like Growth Factor I
Gonadotropin-Releasing Hormone
IGF Type 1 Receptor
Steroids
Neurons
Preoptic Area
Hypothalamus
Brain
Reproductive Behavior
Third Ventricle
Presynaptic Terminals
Progesterone Receptors
Estrogen Receptors
Progesterone
Estradiol
Hormones

ASJC Scopus subject areas

  • Endocrinology

Cite this

Differential effects of hypothalamic IGF-I on gonadotropin releasing hormone neuronal activation during steroid-induced LH surges in young and middle-aged female rats. / Sun, Yan; Todd, Brigitte J.; Thornton, Kimberly; Etgen, Anne M.; Neal-Perry, Genevieve.

In: Endocrinology, Vol. 152, No. 11, 11.2011, p. 4276-4287.

Research output: Contribution to journalArticle

Sun, Yan ; Todd, Brigitte J. ; Thornton, Kimberly ; Etgen, Anne M. ; Neal-Perry, Genevieve. / Differential effects of hypothalamic IGF-I on gonadotropin releasing hormone neuronal activation during steroid-induced LH surges in young and middle-aged female rats. In: Endocrinology. 2011 ; Vol. 152, No. 11. pp. 4276-4287.
@article{92a9e5831fed44c48d07d9eea9939c9a,
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 Gn RH neurons in young rats and for robustGnRHrelease 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.",
author = "Yan Sun and Todd, {Brigitte J.} and Kimberly Thornton and Etgen, {Anne M.} and Genevieve Neal-Perry",
year = "2011",
month = "11",
doi = "10.1210/en.2011-1051",
language = "English (US)",
volume = "152",
pages = "4276--4287",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "11",

}

TY - JOUR

T1 - Differential effects of hypothalamic IGF-I on gonadotropin releasing hormone neuronal activation during steroid-induced LH surges in young and middle-aged female rats

AU - Sun, Yan

AU - Todd, Brigitte J.

AU - Thornton, Kimberly

AU - Etgen, Anne M.

AU - Neal-Perry, Genevieve

PY - 2011/11

Y1 - 2011/11

N2 - 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 Gn RH neurons in young rats and for robustGnRHrelease 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.

AB - 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 Gn RH neurons in young rats and for robustGnRHrelease 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.

UR - http://www.scopus.com/inward/record.url?scp=80054945592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054945592&partnerID=8YFLogxK

U2 - 10.1210/en.2011-1051

DO - 10.1210/en.2011-1051

M3 - Article

C2 - 21914776

AN - SCOPUS:80054945592

VL - 152

SP - 4276

EP - 4287

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 11

ER -