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NEUROENDOCRINOLOGY
LETTERS
including
Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology
and Human Ethology, ISSN 0172–780X
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NEL
Vol.24 Nos.3/4, Jun-Aug 2003
ORIGINAL ARTICLE
Early hyperandrogenicity and insulin resistance
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2003;
24:241–248
pii: NEL243403A15
PMID: 14523364
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Neonatal
hypothalamic androgenization in the female rat induces changes
in peripheral insulin sensitivity and adiposity function at
adulthood
Mario
Perelló 1, Daniel Castrogiovanni 1, Griselda
Moreno 1, Rolf C. Gaillard 2 & Eduardo Spinedi
1
1.
Neuroendocrine Unit, Multidisciplinary Institute on Cell Biology
(CONICET-CICPBA), La Plata, Argentina;
2.
Division of Endocrinology, Diabetology & Metabolism, University
Hospital (CHUV), Lausanne, Switzerland.
Submitted:
May 21, 2003
Accepted: July 6, 2003
Key
words:
leptin, glucose load, glucocorticoid, sex steroids, PCOS
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Abstract
It
is recognized that there exists a link between hyperandrogenicity
and insulin resistance. OBJECTIVE: By using the neonatally
androgenized female rat we explored whether this treatment
modifies peripheral insulin sensitivity and visceral fat function
at adulthood.
EXPERIMENTAL
DESIGNS: On day 5 of age, female Sprague-Dawley pups were
injected, sub cutaneous, with either 50 ml of sterile corn
oil alone (CT) or containing 1.25 mg of testosterone propionate
(TP) and further used for experimentation on day 100 of age.
CT and TP rats were killed by decapitation in non-fasting
condition and blood samples were kept frozen for measurement
of different metabolites. Immediately after sacrifice, freshly
dissected visceral fat pads were used for isolation of adipocytes,
these cells were then incubated with medium alone or containing
different concentrations of insulin in order to determine
leptin secreted into the medium. Additionally, in vivo metabolic
responses to intravenous high glucose load were performed
in, 24hour-fasting,
CT and TP rats.
RESULTS:
We found that neonatal androgenization induced adult animals
displaying higher visceral adiposity mass, body weight and
leptinemia than CT rats. No group differences were found in
basal circulating levels of several hormones and metabolic
parameters. The results of the high glucose load 90-min test
indicated that TP and CT rats developed similar glycemia but
this accounted because of an early significantly higher peak
values of circulating insulin in TP than in CT rats, regardless
of similar enhancement in circulating glucocorticoid concentrations
in both groups. While high glucose load significantly increased,
over the baseline, circulating leptin concentrations as early
as 30 min post-glucose in CT rats, in TP animals, it significantly
enhanced leptinemia only by the end of the test. Finally,
results of in vitro incubations of isolated visceral adipocytes
indicated that cells from androgenized rats spontaneously
released more leptin than control cells, although they were
less responsive than CT cells to insulin-induced leptin output.
CONCLUSION:
Our study strongly supports the hypothesis that development
of insulin resistance seems to be dependent on early hyperandrogenicity.
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__________________________________________________________
Copyright © Neuroendocrinology Letters 2003
Society of Integrated Sciences
All rights reserved. No part may be reproduced, stored in a
retrieval system, or transmitted in any form or by any means,
electronic, mechanical, photocopying, recording, or ortherwise,
without prior written permission from the Editor-in-Chief.
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