The overall goal of this proposed research is to investigate the development of the brain-pituitary-adrenal axis in the mammalian fetus. This includes determining: (1) if the drive to ACTH secretion increases during gestation and (2) if there is an increase in the ratio of bioactive to immunoreactive ACTH in fetal plasma close to term which correlates with the increase in fetal plasma cortisol occurring during this time. The chronically cannulated lamb fetus is the animal model chosen for study. It is possible to study brain-pituitary-adrenal relationships in this model in the absence of complications caused by the presence of anesthesia and surgical trauma, both of which are inherent in experiments on acutely prepared animals. The information derived from these proposed studies will further our understanding of mechanisms regulating basal activity in an endocrine system necessary for preparing the fetus for birth and in some species, necessary for the initiation of labor. Increasing our understanding of the mechanisms determining the patterns of change in basal fetal plasma cortisol and ACTH levels during the latter part of gestation are essential for furthering our knowledge of the development processes which culminate in the birth of a healthy infant.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HD011210-13
Application #
3485031
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1978-09-29
Project End
1994-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
13
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Su, Yixin; Carey, Luke C; Rose, James C et al. (2013) Antenatal glucocorticoid exposure enhances the inhibition of adrenal steroidogenesis by leptin in a sex-specific fashion. Am J Physiol Endocrinol Metab 304:E1404-11
Su, Yixin; Carey, Luke C; Rose, James C et al. (2012) Leptin alters adrenal responsiveness by decreasing expression of ACTH-R, StAR, and P450c21 in hypoxemic fetal sheep. Reprod Sci 19:1075-84
Valego, Nancy K; Rose, James C (2010) A specific CRH antagonist attenuates ACTH-stimulated cortisol secretion in ovine adrenocortical cells. Reprod Sci 17:477-86
Carey, Luke C; Tatter, Stephen B; Rose, James C (2009) Cortisol infusion in late-gestation hypothalamo-pituitary disconnected sheep fetus restores pituitary cell responsiveness to arginine vasopressin. Am J Physiol Endocrinol Metab 296:E300-4
Carey, Luke C; Tatter, Stephen B; Rose, James C (2007) Ontogeny and effects of hypothalamic pituitary disconnection on formation of inositol trisphosphate in fetal sheep pituitary cells. Endocrinology 148:1440-4
Carey, Luke C; Su, Yixin; Valego, Nancy K et al. (2006) Infusion of ACTH stimulates expression of adrenal ACTH receptor and steroidogenic acute regulatory protein mRNA in fetal sheep. Am J Physiol Endocrinol Metab 291:E214-20
Valego, Nancy K; Su, Yixin; Carey, Luke C et al. (2005) Hypothalamic-pituitary disconnection in fetal sheep blocks the peripartum increases in adrenal responsiveness and adrenal ACTH receptor expression. Am J Physiol Regul Integr Comp Physiol 289:R410-R417
Su, Yixin; Carey, Luke C; Valego, Nancy K et al. (2005) Developmental changes in adrenocorticotrophin (ACTH)-induced expression of ACTH receptor and steroid acute regulatory protein mRNA in ovine fetal adrenal cells. J Soc Gynecol Investig 12:416-20
Chen, Kai; Carey, Luke C; Liu, Jingfang et al. (2005) The effect of hypothalamo-pituitary disconnection on the renin-angiotensin system in the late-gestation fetal sheep. Am J Physiol Regul Integr Comp Physiol 288:R1279-87
Wang, J J; Valego, N K; Su, Y et al. (2004) Developmental aspects of ovine adrenal adrenocorticotropic hormone receptor expression. J Soc Gynecol Investig 11:27-35

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