Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12202/554
Title: Functional interaction between estrogen and insulin -like growth factor-I in the regulation of adrenergic signaling and female reproductive function
Authors: Quesada, Arnulfo
Keywords: Neurosciences.
Issue Date: 2001
Publisher: ProQuest Dissertations & Theses
Citation: Source: Dissertation Abstracts International, Volume: 63-01, Section: B, page: 1140.;Advisors: Anne M. Etgen.
Abstract: We are interested in estradiol (E2) regulation of noradrenergic G-protein coupled receptor signal transduction in the preoptic area (POA) and hypothalamus (HYP); brain areas that govern female reproductive function. E2 action in these brain regions modifies several cellular and molecular components of norepinephrine (NE) neurotransmission, including NE receptor expression and coupling to intracellular effectors. The mechanism(s) by which E2 regulates adrenergic receptor (AR) signal transduction in the POA and HYP is/are still unclear. E2 also regulates protein tyrosine kinases (PTKs) in cell cultures and reproductive tissues. Furthermore, these PTKs can influence signaling by NE receptors. Insulin-like growth factor-I (IGF-I), IGF-I receptors, which are PTKs, and IGF-I binding proteins are locally synthesized by glia and neurons of the HYP and can be regulated by E 2. Given that E2 modulates both NE receptor-mediated signaling and IGF-I function, we hypothesized that E2 action on NE signaling might involve IGF-I action in the POA and HYP. Adult Spraque-Dawley female rats were ovariohysterectomized and treated in vivo with E2 for two days prior to testing. Pharmacological modulation of cAMP levels in brain slices was used as the marker of intracellular interactions among E2, IGF-I, and NE receptors. IGF-I enhances NE-stimulated cAMP accumulation via modulation of alpha1-AR potentiation of adenylyl cyclase, but only if slices are derived from E2-primed rats. E2 priming significantly increases [125]I-IGF-I binding density in POA and HYP. E2 increases alpha1B-AR expression in POA and HYP of female rats; these receptors are believed to mediate the excitatory component of NE action on sexual behavior. Because modulation of alphal-AR signaling by IGF-1 and the level of alpha 1B-AR expression in the POA and HYP are both E2-regulated events, we examined the possibility that E2-induced expression of alpha1B-AR in the POA and HYP might be IGF-1R mediated. In vivo blockade of IGF-IR during E2 priming prevents alpha 1B-adrenoceptor expression, LH release, significantly inhibits sexual behavior and blocks IGF-I modulation of alpha1-AR signaling, all of which are E2 regulated events. Therefore, we can speculate that the changes in noradrenergic signal transduction resulting from E 2 and IGF-I action in the brain control reproductive function.
URI: https://ezproxy.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:3039071
https://hdl.handle.net/20.500.12202/554
Appears in Collections:Albert Einstein College of Medicine: Doctoral Dissertations

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.