The present study is designed to test the hypothesis that fetal splanchnic nerves are necessary for normal physiological fetal adrenocortical function in response to acute and chronic hypoxemia. This hypothesis will be tested utilizing fetal sheep with splanchnic nerve ablation and it is anticipated that adrenocortical responses will be blunted after splanchnic nerve section. Selected vascular, hormonal, cellular, and molecular responses of the fetal adrenal and sympathetic spinal cord will be quantified in response to an acute 60 minute (Aim 1) or a chronic 24 hour (Aim 2) hypoxemic challenge induced by infusion of nitrogen into the maternal trachea. Hormonal endpoints will be fetal cortisol, ACTH, AVP, PGE2, catecholamines, and maternal cortisol plasma concentrations. Molecular determinations will include immunocytochemical staining, in situ hybridization, and Northern and Western analysis of steroidogenic enzymes, CRH, c-fos, c-jun, PNMT, tyrosine hydroxylase, and glucocorticoid receptors in the fetal adrenal and sympathetic spinal cord.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK051234-02
Application #
2654553
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Sato, Sheryl M
Project Start
1997-04-21
Project End
2001-01-31
Budget Start
1998-02-06
Budget End
1999-01-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Cornell University
Department
Physiology
Type
Schools of Veterinary Medicine
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Zambrano, E; Nathanielsz, P W; McDonald, T J (2001) Prenatal and postnatal ovine adrenal cell responses to prostaglandin E(2). J Soc Gynecol Investig 8:149-57
Berghorn, K A; Li, C; Nathanielsz, P W et al. (2000) VIP innervation: sharp contrast in fetal sheep and baboon adrenal glands suggests differences in developmental regulation. Brain Res 877:271-80