HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/1/R198    most recent 00349.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by He, J. Articles by Devaskar, S. U. Search for Related Content PubMed PubMed Citation Articles by He, J. Articles by Devaskar, S. U.

DEVELOPMENT AND TISSUE PLASTICITY

Postnatal glucocorticoid exposure alters the adult phenotype

³Divisions of Neonatology and Developmental Biology, Departments of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, California 90095; and ¹Schools of Medicine and ²Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15213

Submitted 25 June 2003 ; accepted in final form 26 February 2004

We examined the effect of six doses of dexamethasone (Dex) administered daily (2–7 days of age) to postnatal rats on body weight gain, food and water intake, peripheral hormonal/metabolic milieu, and hypothalamic neuropeptides that regulate food intake. We observed a Dex-induced acute (3 days of age) suppression of endogenous corticosterone and an increase in circulating leptin concentrations that were associated with a decrease in body weight in males and females. Followup during the suckling, postsuckling, and adult stages (7–120 days of age) revealed hypoleptinemia in males and females, and hypoinsulinemia, a relative increase in the glucose-to-insulin ratio, and a larger increase in skeletal muscle glucose transporter (GLUT 4) concentrations predominantly in the males, reflective of a catabolic state associated with a persistent decrease in body weight gain. The increase in the glucose-to-insulin ratio and hyperglycemia was associated with an increase in water intake. In addition, the changes in the hormonal/metabolic milieu were associated with an increase in hypothalamic neuropeptide Y content in males and females during the suckling phase, which persisted only in the 120-day-old female with a transient postnatal decline in -melanocyte-stimulating hormone and corticotropin-releasing factor. This increase in neuropeptide Y (NPY) during the suckling phase in males and females was associated with a subsequent increase in adult food intake that outweighed the demands of body weight gain. In contrast to the adult hypothalamic findings, cerebral ventricular dilatation was more prominent in adult males. We conclude that postnatal Dex treatment causes permanent sex-specific changes in the adult phenotype, setting the stage for future development of diabetes (increased glucose:insulin ratio), obesity (increased NPY and food intake), and neurological impairment (loss of cerebral volume).

development; food intake; neuropeptide Y; glucose transporters

This article has been cited by other articles:

				M. Garg, M. Thamotharan, L. Rogers, S. Bassilian, W. N. P. Lee, and S. U. Devaskar Glucose metabolic adaptations in the intrauterine growth-restricted adult female rat offspring Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1218 - E1226. [Abstract] [Full Text] [PDF]

				M. Thamotharan, B.-C. Shin, D. T. Suddirikku, S. Thamotharan, M. Garg, and S. U. Devaskar GLUT4 expression and subcellular localization in the intrauterine growth-restricted adult rat female offspring Am J Physiol Endocrinol Metab, May 1, 2005; 288(5): E935 - E947. [Abstract] [Full Text] [PDF]

				E. D. Bruder, P. C. Lee, and H. Raff Dexamethasone treatment in the newborn rat: fatty acid profiling of lung, brain, and serum lipids J Appl Physiol, March 1, 2005; 98(3): 981 - 990. [Abstract] [Full Text] [PDF]

				A. R. Stark Pharmacology Review: Risks and Benefits of Postnatal Corticosteroids NeoReviews, February 1, 2005; 6(2): e99 - e103. [Full Text] [PDF]