Abstract

This study is designed to examine the influence of prenatal exposure to ethanol on the development of sexually dimorphic GH release that first occurs at puberty. Both the perinatal period (when programming of cyclicity occurs) and the prepubertal period (when cyclicity is initiated) will be examined. Because GH cyclicity is influenced by gender, analyses will also be conducted to determine if vulnerability to ethanol is sexually dimorphic. The following aspects of GH development and regulation of cyclicity will be examined: l) differential sensitivity to GH and insulin-like growth factor feedback 2) development of neurotransmitter regulation 3) establishment of connections between somatostatin (SRIF) and GH- releasing factor (GRF) neurons 4) hypothalamic SRIF and GRF peptide and mRNA 5) capacity of somatotrophes to synthesize GH 6) sensitivity of somatotrophs to SRIF and GRF with particular attention to the cAMP second messenger system The rat will be used as a model in this study because knowledge of the rat endocrine system is extensive and because this species is also vulnerable to ethanol-induced disruption of the GH system. Dams will be fed a liquid diet with 36% of the calories derived from ethanol. Studies examining the dynamic interaction between the hypothalamus and pituitary in the regulation of GH release will use a novel perfusion system established in this laboratory. This is an in vitro system co-perifusing the hypothalamus and dispersed pituitaries in a single chamber. This system permits the systematic examination of factors influencing GH release and the simultaneous analysis of hypothalamic and pituitary hormones by radioimmunoassay (RIA) of the perfusate. The influence of ethanol on the development of the GH regulatory system will also be evaluated by determination of releasing factor content and mRNAs and GH content by RIA and Northern hybridization. The cAMP messenger system for SRIF and GRF will be analyzed by measuring somatotroph content of cAMP, cAMP binding and protein kinase activity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA009483-01A1
Application #
3113546
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1993-09-01
Project End
1996-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Northern Illinois University
Department
Type
Schools of Arts and Sciences
DUNS #
City
De Kalb
State
IL
Country
United States
Zip Code
60115