The fetal alcohol syndrome : influence of ethanol on chick embryo brain cAMP and protein kinase / by John William Boyd.
| Author/creator | Boyd, John William author. |
| Other author | Kalmus, Gerhard W., degree supervisor. |
| Other author | East Carolina University. Department of Biology. |
| Format | Theses and dissertations |
| Production | 1983. |
| Description | vii, 93 leaves : illustrations ; 28 cm |
| Supplemental Content | Access via ScholarShip |
| Subjects |
| Summary | Maternal ethanol consumption during pregnancy is known to be detrimental to embryonic (and/or fetal) growth. A broad range of developmental abnormalities including growth deficiency, central nervous system dysfunction, atypical facial appearances and various other malformations (cardiovascular, renogenital, and skeletal) are characteristic of ethanol's influence on development. This group of malformations is termed the Fetal Alcohol Syndrome (FAS). Although the morphological characteristics of FAS are well defined, the underlying molecular mechanisms responsible for FAS are not understood. The two objectives of this thesis were (1) to develop the chick embryo as a suitable model for study of FAS and (2) to study ethanol's influence on a molecular mechanism involved with normal growth and differentiation. The first objective was accomplished by dosing the chick embryo via the egg airspace and measuring the influence of ethanol on chick embryo growth (weight) at 8, 10, and 12 days of development. Ethanol injected into the egg airspace at the start of incubation and in concentrations of 33 and 65 mg ethanol/100 g whole egg resulted in a dose dependent growth suppression as compared to appropriate controls. Gas chromatographic determinations of ethanol in yolk, albumen and embryo blood indicated that ethanol diffused evenly throughout the egg, was cleared in a linear rate, and was detectable at 12 days of embryonic development. Because ethanol was known to alter fetal hormone levels it was our working hypothesis that the molecular mechanism of ethanol induced growth suppression might be mediated via the influence of ethanol on a hormone-related intracellular mechanism. This intracellular mechanism involves the nucleotide cyclic adenosine 3',5'-monophosphate (cAMP) and the enzyme protein kinase. The influences of ethanol on cAMP levels, ability of protein kinase to bind cAMP (regulatory subunit of protein kinase) and protein kinase catalytic activity were studied. All biochemical studies were restricted to embryo brain as the tissue source because microcephaly and mental retardation are key characteristics of FAS. Brains were removed from embryos receiving the same ethanol dosages which had previously been shown to induce growth suppression. Ethanol was found to elevate brain cAMP levels in 8 and 10 day chick embryos. Ethanol increased the catalytic efficiency of protein kinase (in the presence of exogenous cAMP) in 8 day embryo brain but did not significantly alter the ability of 8 day chick embryo brain homogenate to bind cAMP. Previous investigators have correlated increased cAMP levels with growth inhibition, but few studies have examined the relationship between ethanol and protein kinase or the influences of ethanol on protein phosphorylation and overall growth. The results of this work support the hypothesis that ethanol does influence a hormone-related intracellular mechanism involved with growth. |
| General note | "Presented to the faculty of the Department of Biology ... in partial fulfillment of the requirements for the degree Master of Science in Biology." |
| General note | Advisor: Gerhard W. Kalmus |
| Dissertation note | M.S. East Carolina University 1983 |
| Bibliography note | Includes bibliographical references (leaves 77-84). |
| Genre/form | dissertations. |
| Genre/form | Academic theses. |
| Genre/form | Academic theses. |
| Genre/form | Thèses et écrits académiques. |