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      Differential Sensitivity to ACTH, but Not Stress, in Two Sources of Outbred Sprague-Dawley Rats

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          Abstract

          Adrenocorticotropic hormone (ACTH) is the major regulator of adrenocortical steroidogenesis in mammals. By comparing the sensitivity to ACTH of isolated adrenocortical cells from two sources of the same strain (Sprague-Dawley, SD) of outbred rats, we have identified a source of rat with low sensitivity to ACTH in vitro. Cells isolated from Holtzman SD rats had a high sensitivity to ACTH (minimal effective concentration 50 pg/ml), whereas Taconic SD rats had a low sensitivity (minimal effective concentration 250 pg/ml; maximal steroidogenesis <50% of Holtzman cells). The responsiveness to analogues of cyclic adenosine monophosphate and cholesterol was also significantly lower in Taconic SD rats. Taconic adrenals were smaller, had significantly more mitochondria per cell, but approximately 20% less total lipid droplet volume per cell. There was no difference in latency to ACTH in vitro; however, steroidogenesis plateaued in Taconic cells after 25 min, while Holtzman cells secreted corticosterone almost linearly for at least 120 min. By contrast, the cyclic adenosine monophosphate secretion increased at the same rate for at least 120 min in cells from both sources. There were no differences between cells from the two sources in immunoreactive steroidogenic enzyme content. In vivo, the magnitude of the ACTH and corticosterone responses to two types of stress were similar in both sources. The thymus glands of Holtzman rats were significantly larger than those of Taconic rats. It is concluded that: (1) reduced sensitivity to ACTH in vitro in Taconic SD rats results from differences in the later stages of the steroidogenic pathway; (2)  factors in addition to ACTH are required for maximal steroidogenesis in Taconic SD rats; (3) a comparison of the steroidogenic pathways in adrenal cells from these two sources of outbred rats should be useful in further delineating the relative importance of putative intracellular signalling mechanisms involved in initiation and maintenance of steroidogenesis, and (4) these data suggest that different sources of the same strain of rats sufficiently diverge over time to become separate strains (‘substrains’). Overreliance on a single source of laboratory rodent may obscure natural variability in endocrine responses to stress and provide a misleading indication of homogeneity of responses.

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          Most cited references 6

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          Maternal Care, Hippocampal Glucocorticoid Receptors, and Hypothalamic-Pituitary-Adrenal Responses to Stress

           D. Liu (1997)
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            Maternal regulation of the hypothalamic-pituitary-adrenal axis in the infant rat: the roles of feeding and stroking

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              Peripheral-type benzodiazepine/diazepam binding inhibitor receptor: biological role in steroidogenic cell function

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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                1998
                June 1998
                19 June 1998
                : 67
                : 6
                : 403-411
                Affiliations
                Department of Biology, Boston University, Boston, Mass., USA
                Article
                54339 Neuroendocrinology 1998;67:403–411
                10.1159/000054339
                9662720
                © 1998 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
                Pages: 9
                Categories
                Corticotropin and Pro-Opiomelanocortin

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