Hypothalamic Insulin-like Growth Factor-I Receptors Are Necessary for Hormone-dependent Luteinizing Hormone Surges: Implications for Female Reproductive Aging

Overview

Journal Endocrinology

Publisher Oxford University Press

Specialty Endocrinology

Date 2010 Jan 26

PMID 20097715

Citations 15

Authors

Brigitte J Todd

Zaher O Merhi

Jun Shu

Anne M Etgen

Genevieve S Neal-Perry

Affiliations

Soon will be listed here.

Abstract

Brain IGF-I receptors are required for maintenance of estrous cycles in young adult female rats. Circulating and hypothalamic IGF-I levels decrease with aging, suggesting a role for IGF-I in the onset of reproductive senescence. Therefore, the present study investigated potential mechanisms of action of brain IGF-I receptors in the regulation of LH surges in young adult and middle-aged rats. We continuously infused IGF-I, the selective IGF-I receptor antagonist JB-1, or vehicle into the third ventricle of ovariectomized young adult and middle-aged female rats primed with estradiol and progesterone. Pharmacological blockade of IGF-I receptors attenuated and delayed the LH surge in young adult rats, reminiscent of the LH surge pattern that heralds the onset of reproductive senescence in middle-aged female rats. Infusion of IGF-I alone had no effect on the LH surge but reversed JB-1 attenuation of the surge in young females. In middle-aged rats, infusion of low doses of IGF-I partially restored LH surge amplitude, and infusion of JB-1 completely obliterated the surge. Intraventricular infusion of IGF-I or JB-1 did not modify pituitary sensitivity to exogenous GnRH or GnRH peptide content in the anterior or mediobasal hypothalamus in either young or middle-aged rats. These findings support the hypothesis that brain IGF-I receptor signaling is necessary for GnRH neuron activation under estrogen-positive feedback conditions and that decreased brain IGF-I signaling in middle-aged females contributes, in part, to LH surge dysfunction by disrupting estradiol-sensitive processes that affect GnRH neuron activation and/or GnRH release.

Citing Articles

Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain.

Jurkowski M, Bettio L, Woo E, Patten A, Yau S, Gil-Mohapel J Front Cell Neurosci. 2020; 14:576444.

PMID: 33132848 PMC: 7550688. DOI: 10.3389/fncel.2020.576444.

A Prospective Study of Dairy-Food Intake and Early Menopause.

Purdue-Smithe A, Whitcomb B, Manson J, Hankinson S, Rosner B, Troy L Am J Epidemiol. 2018; 188(1):188-196.

PMID: 30239575 PMC: 6321800. DOI: 10.1093/aje/kwy212.

Nasal delivery of nerve growth factor rescue hypogonadism by up-regulating GnRH and testosterone in aging male mice.

Luo J, Yang Y, Zhang T, Su Z, Yu D, Lin Q EBioMedicine. 2018; 35:295-306.

PMID: 30131307 PMC: 6161474. DOI: 10.1016/j.ebiom.2018.08.021.

Neuroanatomical Framework of the Metabolic Control of Reproduction.

Hill J, Elias C Physiol Rev. 2018; 98(4):2349-2380.

PMID: 30109817 PMC: 6170978. DOI: 10.1152/physrev.00033.2017.

The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1).

Wolfe A, Divall S, Wu S Front Neuroendocrinol. 2014; 35(4):558-72.

PMID: 24929098 PMC: 4175134. DOI: 10.1016/j.yfrne.2014.05.007.

References

Werther G, Hogg A, Oldfield B, McKinley M, Figdor R, Mendelsohn F . Localization and Characterization of Insulin-Like Growth Factor-I Receptors in Rat Brain and Pituitary Gland Using in vitro Autoradiography and Computerized Densitometry* A Distinct Distribution from Insulin Receptors. J Neuroendocrinol. 2009; 1(5):369-77. DOI: 10.1111/j.1365-2826.1989.tb00131.x. View

Wise P, Smith M, Dubal D, Wilson M, Rau S, Cashion A . Neuroendocrine modulation and repercussions of female reproductive aging. Recent Prog Horm Res. 2002; 57:235-56. DOI: 10.1210/rp.57.1.235. View

Gottsch M, Cunningham M, Smith J, Popa S, Acohido B, Crowley W . A role for kisspeptins in the regulation of gonadotropin secretion in the mouse. Endocrinology. 2004; 145(9):4073-7. DOI: 10.1210/en.2004-0431. View

Smith J, Cunningham M, Rissman E, Clifton D, Steiner R . Regulation of Kiss1 gene expression in the brain of the female mouse. Endocrinology. 2005; 146(9):3686-92. DOI: 10.1210/en.2005-0488. View

Maffucci J, Walker D, Ikegami A, Woller M, Gore A . NMDA receptor subunit NR2b: effects on LH release and GnRH gene expression in young and middle-aged female rats, with modulation by estradiol. Neuroendocrinology. 2007; 87(3):129-41. PMC: 2671961. DOI: 10.1159/000111136. View

Chung Y, Shin C, Joo K, Kim M, Cha C . Region-specific alterations in insulin-like growth factor receptor type I in the cerebral cortex and hippocampus of aged rats. Brain Res. 2002; 946(2):307-13. DOI: 10.1016/s0006-8993(02)03041-x. View

Naftolin F, Garcia-Segura L . Phasic synaptic remodeling of the rat arcuate nucleus during the estrous cycle depends on insulin-like growth factor-I receptor activation. J Neurosci Res. 1999; 55(3):286-92. DOI: 10.1002/(SICI)1097-4547(19990201)55:3<286::AID-JNR3>3.0.CO;2-4. View

Le W, Wise P, Murphy A, Coolen L, Hoffman G . Parallel declines in Fos activation of the medial anteroventral periventricular nucleus and LHRH neurons in middle-aged rats. Endocrinology. 2001; 142(11):4976-82. DOI: 10.1210/endo.142.11.8470. View

Quesada A, Etgen A . Insulin-like growth factor-1 regulation of alpha(1)-adrenergic receptor signaling is estradiol dependent in the preoptic area and hypothalamus of female rats. Endocrinology. 2001; 142(2):599-607. DOI: 10.1210/endo.142.2.7946. View

10.

Cappola A, Xue Q, Ferrucci L, Guralnik J, Volpato S, Fried L . Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women. J Clin Endocrinol Metab. 2003; 88(5):2019-25. DOI: 10.1210/jc.2002-021694. View

11.

van der Beek E, van Oudheusden H, Buijs R, van der Donk H, Van Den Hurk R, Wiegant V . Preferential induction of c-fos immunoreactivity in vasoactive intestinal polypeptide-innervated gonadotropin-releasing hormone neurons during a steroid-induced luteinizing hormone surge in the female rat. Endocrinology. 1994; 134(6):2636-44. DOI: 10.1210/endo.134.6.8194489. View

12.

LIEBERMAN M, Maurer R, Gorski J . Estrogen control of prolactin synthesis in vitro. Proc Natl Acad Sci U S A. 1978; 75(12):5946-9. PMC: 393093. DOI: 10.1073/pnas.75.12.5946. View

13.

Kovacs P, Parlow A, Karkanias G . Effect of centrally administered insulin on gonadotropin-releasing hormone neuron activity and luteinizing hormone surge in the diabetic female rat. Neuroendocrinology. 2003; 76(6):357-65. DOI: 10.1159/000067585. View

14.

Matsui H, Takatsu Y, Kumano S, Matsumoto H, Ohtaki T . Peripheral administration of metastin induces marked gonadotropin release and ovulation in the rat. Biochem Biophys Res Commun. 2004; 320(2):383-8. DOI: 10.1016/j.bbrc.2004.05.185. View

15.

Messager S, Chatzidaki E, Ma D, Hendrick A, Zahn D, Dixon J . Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc Natl Acad Sci U S A. 2005; 102(5):1761-6. PMC: 545088. DOI: 10.1073/pnas.0409330102. View

16.

Bartke A, Chandrashekar V, Dominici F, Turyn D, Kinney B, Steger R . Insulin-like growth factor 1 (IGF-1) and aging: controversies and new insights. Biogerontology. 2003; 4(1):1-8. DOI: 10.1023/a:1022448532248. View

17.

Gerhold L, Rosewell K, Wise P . Suppression of vasoactive intestinal polypeptide in the suprachiasmatic nucleus leads to aging-like alterations in cAMP rhythms and activation of gonadotropin-releasing hormone neurons. J Neurosci. 2005; 25(1):62-7. PMC: 6725194. DOI: 10.1523/JNEUROSCI.3598-04.2005. View

18.

Rubin B, Bridges R . Alterations in luteinizing hormone-releasing hormone release from the mediobasal hypothalamus of ovariectomized, steroid-primed middle-aged rats as measured by push-pull perfusion. Neuroendocrinology. 1989; 49(3):225-32. DOI: 10.1159/000125121. View

19.

Arias P, Carbone S, Szwarcfarb B, Feleder C, Rodriguez M, Scacchi P . Effects of aging on N-methyl-D-aspartate (NMDA)-induced GnRH and LH release in female rats. Brain Res. 1996; 740(1-2):234-8. DOI: 10.1016/s0006-8993(96)00862-1. View

20.

Mora O, Cabrera M, Sanchez-Criado J . Hormonal pattern of the pheromonal restoration of cyclic activity in aging irregularly cycling and persistent-estrus female rats. Biol Reprod. 1994; 51(5):920-5. DOI: 10.1095/biolreprod51.5.920. View