Publication Date

1997

Document Type

Dissertation/Thesis

First Advisor

Conway, Sonya

Degree Name

M.S. (Master of Science)

Department

Department of Biological Sciences

LCSH

Somatomedin||Somatotropin||Fetal alcohol syndrome||Biological control systems

Abstract

This study investigates the effect of fetal ethanol (ETOH) exposure on the development of IGF-1 feedback regulation of the GH axis. We examined at what developmental stage ETOH interferes with IGF-1 modulation of GH release and whether this effect is sexually dimorphic. Pregnant dams were fed: 1) a liquid ETOH diet, 2) an isocaloric liquid control diet, or 3) lab chow. Tissue from 30-(prepubertal) and 60- (postpubertal)-day-old offspring of each diet were removed and the response to stimuli was determined in a hypothalamic-pituitary co-perfusion system. Tissues were perfused with clonidine, an ct2-adrenergic agonist which mimics the endogenous hypothalamic trigger for GH release. To test the sensitivity of the tissue to feedback regulation, clonidine was perfused in combination with IGF-1 (which inhibits clonidine-induced GH release). Timed fractions were assayed for GH, GRF, and SRIF content. Pituitaries from 30-day-old offspring were separately tested to identify the site of fetal ETOH vulnerability. Pituitaries were perfused with GRF or IGF-1 separately and in combination to evaluate changes in sensitivity of somatotrophs in mediating GH feedback. Results of this study indicate that a 2 stimulated GH release is correlated with increased GRF and decreased SRIF release. However, after puberty this response is blunted in females. In contrast, IGF-1 feedback occurs both before and after puberty in both sexes and corresponds to changes in secretion of both releasing factors. In utero ETOH exposure dampened sensitivity of the GH axis to these stimuli. Most evident was a depressed IGF-1 feedback associated with sexually dimorphic differences in vulnerability of releasing factors at 30 days of age. Altered sensitivity to IGF-1 also occurred at the pituitary level. In regard to ct2 sensitivity, ETOH marginally inhibited GH release from male tissue at 30 days of age and was associated with a diminished GRF response to stimulation. After puberty, sensitivity to ETOH was more apparent with blunted responses of both releasing factors. In summary, ETOH disrupts sensitivity to IGF-1 at both the hypothalamic and pituitary levels of the GH axis, and therefore may contribute to changes in circulating levels of GH.

Comments

Includes bibliographical references (pages [101]-126)

Extent

viii, 153 pages

Language

eng

Publisher

Northern Illinois University

Rights Statement

In Copyright

Rights Statement 2

NIU theses are protected by copyright. They may be viewed from Huskie Commons for any purpose, but reproduction or distribution in any format is prohibited without the written permission of the authors.

Media Type

Text

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