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      Neonatal Imprinting and Regulation of Estrogen Receptor Alpha and Beta mRNA Expression by Estrogen in the Pituitary and Hypothalamus of the Male Rat

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          Abstract

          In male rodents, complete reproductive function is critically dependent on adequate estrogen action at different levels of the hypothalamic-pituitary-testicular axis. However, administration of high doses of estrogen during the critical period of neonatal differentiation results in multiple defects in the reproductive axis that disrupt male fertility, the molecular mechanism(s) behind such a phenotype remaining poorly characterized. The aim of this study was twofold: (1) to characterize the effects of neonatal estrogenization upon the pattern of estrogen receptors ERα and ERβ mRNA expression in the pituitary and hypothalamus of the male rat, and (2) to evaluate the ability of estrogen to acutely regulate pituitary and hypothalamic ERα and ERβ mRNA expression in the male rat. To achieve the first goal, groups of male rats were treated on the first day of life with estradiol benzoate (EB; 500 µg/rat), and pituitary and hypothalamic expression of ERα and ERβ mRNA levels were assayed by semiquantitative RT-PCR at different ages from the neonatal period until adulthood (days 1–75 of life). In addition, the mechanism(s) of altered pituitary expression of ERα and ERβ messages in neonatally estrogenized rats was explored by comparison of the effects of neonatal treatment with estrogen or a potent gonadotropin-releasing hormone (GnRH) antagonist. For the second goal, the acute effects of a single dose of EB (12.5–25 µg/rat) on hypothalamic and pituitary ERα and ERβ mRNA expression were assessed in prepubertal and adult male rats. Neonatal estrogenization permanently decreased pituitary ERα and ERβ mRNA expression levels respective to control values at all ages studied. This pattern of response was similar to the short-term effects of neonatal blockade of endogenous GnRH actions. In contrast, neonatal exposure to estrogen transiently increased the hypothalamic expression levels of ERα and ERβ messages. This effect was detected in neonatal (5-day-old), infantile (15-day-old) and prepubertal (30-day-old) rats, and it disappeared at puberty. In addition, estrogen was able to acutely regulate mRNA expression levels of its cognate receptor subtypes in the pituitary and hypothalamus of intact male rats. In adult (75-day-old) males, EB administration (25 µg/rat) induced a significant time-dependent decrease in pituitary ERα and ERβ mRNA levels. In contrast hypothalamic expression of ERα and ERβ messages was increased after acute exposure to EB (12.5 µg/rat) in prepubertal males (30 days old); yet differences in the time course of the response to estrogen were noticed between targets. In conclusion, our data indicate that estrogen is able to neonatally imprint and acutely regulate mRNA expression levels of ERα and ERβ in the pituitary and hypothalamus of the male rat. Regulation of pituitary and hypothalamic ERα and ERβ gene expression by the cognate ligand represents a novel mechanism whereby estrogen modulates its own biological actions upon different levels of the male reproductive axis throughout the life span.

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          Most cited references 10

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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2001
                January 2001
                30 January 2001
                : 73
                : 1
                : 12-25
                Affiliations
                aDepartment of Physiology, University of Córdoba, Córdoba, Spain; bDepartment of Physiology,University of Turku, Turku, Finland
                Article
                54616 Neuroendocrinology 2001;73:12–25
                10.1159/000054616
                11174013
                © 2001 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 7, References: 58, Pages: 14
                Categories
                Neuroendocrine Regulation of Brain Receptor Expression

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