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Vol. 87, No. 3, 2008
Issue release date: April 2008
Section title: GnRH, Gonadotropins, Gonadal Steroids and Reproduction
Neuroendocrinology 2008;87:142–150
(DOI:10.1159/000112421)

Interplay between Dose and Frequency of GnRH Administration in Determining Pituitary Gonadotropin Responsiveness

Hughes V.A. · Boepple P.A. · Crowley, Jr. W.F. · Seminara S.B.
Harvard Reproductive Endocrine Sciences Center and Reproductive Endocrine Unit, Department of Medicine and Department of Pediatrics, Massachusetts General Hospital, Boston, Mass., USA

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Article / Publication Details

First-Page Preview
Abstract of GnRH, Gonadotropins, Gonadal Steroids and Reproduction

Received: 8/30/2007
Published online: 12/7/2007

Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 3

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN

Abstract

Background/Aims: The dose, frequency and contour of GnRH stimulation of the pituitary gonadotrope have been shown to be independent variables influencing pituitary LH secretion. The dynamic interaction between these variables during physiological and pathophysiological states has yet to be examined. Methods: Twelve men with GnRH deficiency and idiopathic hypogonadotropic hypogonadism undergoing GnRH therapy participated in a series of studies in which 2 log orders of GnRH doses (2.5–250 ng/kg) were administered at frequencies varying from 0.5 to 8 hourly. Pituitary responses were characterized by pulse amplitudes and nadirs. The relative sensitivity of the gonadotrope to GnRH was defined as that dose of GnRH capable of eliciting an LH pulse amplitude equal to the mean LH amplitude in normal men. Results: As GnRH stimulation of the gonadotrope slowed from 0.5 to 8 hourly, pulse amplitudes of LH increased whereas mean nadirs decreased (p < 0.05). Unique, curvilinear dose-response curves were found for each frequency that demonstrated an increasing slope (p < 0.03) as the frequency of GnRH stimulation slowed. Thus, the relative sensitivity of the gonadotrope increased as the frequency of GnRH stimulation decreased over the range of physiological frequencies tested. Conclusions: We conclude that a delicate interplay exists between the dose and frequency of GnRH stimulation of the gonadotrope that determines pituitary LH gonadotropin responsiveness in the human. Slower frequencies favor increased LH release largely due to decreasing LH nadirs and improved sensitivity of the gonadotropes to GnRH stimulation.


Article / Publication Details

First-Page Preview
Abstract of GnRH, Gonadotropins, Gonadal Steroids and Reproduction

Received: 8/30/2007
Published online: 12/7/2007

Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 3

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN


Copyright / Drug Dosage

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 or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
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 goverment 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.

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