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      Progesterone Promotes Rapid Desensitization of α 1-Adrenergic Receptor Augmentation of cAMP Formation in Rat Hypothalamic Slices

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          Abstract

          We previously demonstrated that norepinephrine (NE) induction of cAMP accumulation in slices of the preoptic area (POA) and middle hypothalamus (MH) is reduced by in vivo administration of progesterone to estradiol-primed rats, apparently by eliminating α<sub>1</sub>-receptor augmentation of β-receptor-stimulated cAMP formation. The present studies examined whether in vitro exposure to progesterone would also depress NE-stimulated cAMP synthesis. POA and MH slices from estradiol-primed females were incubated with 20 n M progesterone for 5-30 min prior to addition of 100 µ M NE. Pre-incubation of slices with progesterone for as little as 5 min significantly suppressed NE-stimulated cAMP formation by greater than 60%. This effect was estrogen-dependent in that progesterone in vitro did not inhibit NE-stimulated cAMP accumulation in slices from ovariectomized rats not pretreated with estradiol. Isoproterenol, a β-adrenergic agonist, elevated cAMP to the same extent in slices from estradiol-primed females incubated with and without progesterone in vitro; however, the α<sub>1</sub>-agonist, phenylephrine, was unable to augment cAMP formation in slices incubated in vitro with progesterone for 5 min prior to drug challenge. To determine whether the rapid effects of progesterone may be exerted at the level of the plasma membrane, we employed progesterone conjugated to bovine serum albumin at carbon 3 (P-3-BSA). Slices from estradiol-primed rats incubated with P-3-BSA for 5 min did not exhibit an α<sub>1</sub>-receptor augmentation of β-receptor-stimulated cAMP accumulation. These data indicate that progesterone may have rapid, non-genomic effects on α<sub>1</sub>-adrenergic receptor coupling to second-messenger systems in the hypothalamus of female rats.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1992
          1992
          07 April 2008
          : 55
          : 1
          : 1-8
          Affiliations
          Departments of Psychiatry and Neuroscience, Albert Einstein College of Medicine, Bronx, N.Y., USA
          Article
          126089 Neuroendocrinology 1992;55:1–8
          10.1159/000126089
          1319002
          c0b55bd9-491e-4e8b-9d1d-533d30c4e7a3
          © 1992 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.

          History
          : 21 January 1991
          : 24 April 1991
          Page count
          Pages: 8
          Categories
          Original Paper

          Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
          Norepinephrine Progesterone cAMP,Hypothalamus Preoptic area α1-Adrenergic receptor, desensitization

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