Different Effects of Castration and Estrogen Administration on Glomerular Injury in Spontaneously Hyperglycemic Otsuka Long-Evans Tokushima Fatty (OLETF) Rats

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Aim: Non-insulin-dependent diabetic mellitus model rats, Otsuka-Long-Evans-Tokushima-Fatty (OLETF), develop diabetic nephropathy presenting with mesangial expansion leading to glomerular sclerosis and thickening of the glomerular basement membrane (GBM), especially in elderly males. The effects of sex hormones and castration on the incidence of diabetes mellitus (DM) have been studied in this strain rat. However, there have been no detailed studies on the effects of castration and sex hormone in the development of diabetic nephropathy. Methods: In this study we examine the effect of castration or estrogen on the development of glomerular injury in OLETF rats. Thirty male OLETF rats and 10 male long-Evans Tokushima Otsuka (LETO) rats as a normal control were used. OLETF rats were divided into three groups: group 1 received sham-operation, group 2 was castrated at 6 weeks, and group 3 was administered 0.1 mg estrogen subcutaneously once a month from 6 weeks to 58 weeks of age and LETO rats were assigned to group 4. Body weight, urinary protein and fasting blood glucose, serum albumin and other serum constituents were investigated every 12 weeks from 12 weeks to 60 weeks of age. In groups 1–3, glucose tolerance test was performed at 38 weeks. Each group was studied morphologically at the end of the experiment (60 weeks of age). Results: Castration attenuated proteinuria and glomerular sclerosis accompanied by an amelioration of glucose tolerance, a decrease in mesangial expansion and an attenuation of the GBM thickening. In contrast, although estrogen equally ameliorated glucose tolerance and attenuated the mesangial expansion and the GBM thickening, estrogen failed to attenuate proteinuria and glomerulosclerosis. A significant increase in glomerular tuft volume, and serum levels of growth hormone, total cholesterol and triglycerides was observed in the estrogen-treated rats as compared with the castrated rats. Conclusion: Besides the mechanisms involved in the development of diabetic nephropathy, other mechanisms may be involved and contribute to the development of glomerulosclerosis in the estrogen-treated rats, leading to a difference in glomerular injury between the castrated and estrogen-treated OLETF rats.

Related collections

Most cited references 2

Record: found
Abstract: found
Article: not found

Estrogen accelerates the development of renal disease in female obese Zucker rats.

Anna Nguyen, Timothy Johnson, Naomi M Gades … (1997)

Renal failure is the primary cause of death in obese Zucker rats (OZR). We previously found that renal injury occurred earlier and with greater severity in female OZR; also, prevention of hyperphagia decreased renal damage in females more than males. To examine the relationship between estrogen (E), hyperphagia, hyperlipidemia, and renal injury in female OZR, we studied four groups from 5 to 10 or 21 weeks of age: Sham-operated (Sham), ovariectomized (Ovx), Ovx with estrogen treatment (Ovx + E), and since Ovx increases food intake, Ovx pair-fed to sham (Ovx-PF). By only six weeks of age, albumin excretion (UAE) increased significantly in Ovx + E (9.9 +/- 4.1 mg/day). Ovx + E also ate least and gained the least weight, but had the highest plasma lipid levels. In contrast, UAE in Ovx did not increase by 10 weeks of age, despite a significantly greater food consumption. The hyperlipidemia of Ovx + E was due primarily to triglycerides. Both plasma triglycerides and renal injury, judged from either histology or UAE, were greatest in the Ovx + E group Fasting plasma glucose was lower and insulin was higher in Ovx + E compared to Ovx rats at 15 weeks of age. Estrogen may promote renal injury in female OZR by increasing the plasma concentration of triglyceride-rich lipoproteins.

0 comments Cited 14 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Somatostatin Analogue Attenuates Estrogen-Induced Augmentation of Glomerular Injury in Spontaneous Hypercholesterolemic Female Imai Rats

Megumi Nakamura, Yuji Ikeda, Makoto Mine … (2001)

Background: Aggravating effect of estrogen replacement therapy on glomerular injury associated with an elevation of growth hormone (GH) levels has been reported. Therefore, in the present study, to clarify an association between GH elevation and the aggravating effect of estrogen on glomerular injury, we investigated the effect of somatostatin, an inhibitor of GH secretion, on glomerular injury in estrogen-treated hypercholesterolemic female Imai rats. Method: Control female rats were assigned to group 1 (Cont, n = 10). Group 2 (Cont-E, n = 10) received estrogen, and groups 3 (Cont-E-LS, n = 10) and 4 (Cont-E-HS) received estrogen and either a low dose of somatostatin analogue or a high dose of somatostatin analogue. Body weight, urinary protein, serum albumin, total cholesterol, triglycerides, blood urea nitrogen and serum creatinine were investigated every 4 weeks from 10 weeks through 30 weeks of age. At 30 weeks of age, rats were studied morphologically. Results: Estrogen administration resulted in an increase in urinary protein excretion rates and serum total cholesterol levels, and aggravated glomerular injury associated with an increase in GH. In contrast, somatostatin treatment reduced both urinary protein excretion rates and total cholesterol levels and attenuated glomerular injury to levels close to those of controls associated with a reduction of GH levels. Conclusion: The results suggest that increased GH levels may contribute to an enhancing effect of estrogen administration on glomerular injury.

0 comments Cited 2 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (publisher-id): NEF

Journal ID (nlm-ta): Nephron

Journal ID (doi): 10.1159/issn.1660-8151

Title: Nephron

Publisher: S. Karger AG

ISSN (Print): 1660-8151

ISSN (Electronic): 2235-3186

Publication date Subscription-year: 2002

Publication date (Print): October 2002

Publication date (Electronic): 18 October 2002

Volume: 92

Issue: 4

Pages: 860-867

Affiliations

From the Department of Internal Medicine, Saga Medical School, Saga, Japan

Article

Publisher ID: 65442 Other ID: Nephron 2002;92:860–867

DOI: 10.1159/000065442

PubMed ID: 12399633

SO-VID: 734df6ba-1752-43b3-87d5-ad1f87892219

License:

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.