M.S. (Master of Science)
Department of Biological Sciences
Somatomedin; Somatotropin; Fetal alcohol syndrome; Biological control systems
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.
Holtzman, Tamara, "The effects of fetal ethanol exposure on the role of IGF-1 in growth hormone feedback in the postnatal rat" (1997). Graduate Research Theses & Dissertations. 5644.
viii, 153 pages
Northern Illinois University
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