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    • Albert Einstein College of Medicine: Doctoral Dissertations
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    • Albert Einstein College of Medicine (AECOM)
    • Albert Einstein College of Medicine: Doctoral Dissertations
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    Estrogen regulation of noradrenergic receptor signaling in the female rat brain

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    Date
    2000
    Author
    Ansonoff, Michael A.
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    Abstract
    The goal of this thesis is to identify key molecular mechanisms by which estrogen regulates noradrenergic receptor signaling in the brain. These mechanisms underlie estrogen facilitation of reproductive behavior and gonadotropin release. Specific studies examine the mechanism by which estrogen promotes uncoupling of noradrenergic receptors from G protein and whether estrogen regulates protein kinase C (PKC) in the hypothalamus (HYP) and preoptic area (POA), brain regions which mediate estrogenic control of female reproductive function.;Estrogen may facilitate reproductive function in part by attenuating alpha 2- and beta-adrenoceptor function in the HYP and POA, both of which can inhibit reproductive function. Presynaptic alpha2-adrenoceptors in the HYP act as autoreceptors that mediate negative feedback inhibition of NE release. Estrogen elevates NE release in the HYP in part by reducing alpha 2-adrenoceptor function, and this is correlated with reduced coupling of alpha2-adrenoceptors to G protein.;Because receptor phosphorylation reduces receptor coupling to G protein, experiments investigated whether estrogen promotes uncoupling of alpha 2- and beta-adrenoceptors by increasing receptor phosphorylation. Female rats were ovariectomized and subsequently injected with either vehicle or 2 mug of estradiol benzoate 48 and 24 hr before killing. These physiological levels of hormone replacement are sufficient to reinstate reproductive behavior and gonadotropin release. Activation of endogenous serine/threonine phosphatases via protamine stimulation or application of exogenous alkaline phosphatase restores alpha2-adrenoceptor coupling to G protein in HYP membranes from estrogen-exposed female rats.;Because phosphorylation of G protein coupled receptors often leads to receptor internalization, other experiments determined whether estrogen treatment modifies the subcellular localization of alpha2- and beta-adrenoceptors in the HYP and POA. Estrogen treatment significantly reduces the percent of internalized alpha2-adrenoceptors in the HYP and of beta-adrenoceptors in the HYP and POA.;Estrogen increases the expression of alpha1b-adrenoceptors in the HYP-POA, and these receptors facilitate reproductive behavior and gonadotropin release. alpha1b-Adrenoceptors activate phospholipase C, stimulating intracellular calcium release and PKC. Because stimulation of PKC is a key element in alpha1b-adrenoceptor signaling, estrogenic regulation of PKC was examined in HYP-POA. Estrogen significantly elevates PKC activity in the POA, but not in the HYP or cortex. The reduction in PKC activity in the POA is not accompanied by detectable alterations in protein levels of PKC isoforms. The elevation of PKC activity in the POA by estrogen has functional significance.;These data suggest two possible mechanisms of estrogen action in the HYP and POA, which may contribute to facilitation of reproductive physiology and behavior. (Abstract shortened by UMI.).
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    https://yulib002.mc.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:9985218
    https://hdl.handle.net/20.500.12202/3919
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    • Albert Einstein College of Medicine: Doctoral Dissertations [1674]

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