Maintaining normal levels of cortisol in response to chronic stress, while retaining the ability to respond to acute stress, is important for ensuring normal fetal growth and development. Long-term hypoxia (LTH) causes adaptations in the fetal hypothalamopituitary- adrenal (HPA) axis that maintain basal cortisol levels but enhance production in response to a secondary stress. Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS) in the adrenal cortex, plays a significant role in regulating cortisol production in the LTH fetus. The production of NO is regulated by eNOS activity which can be altered via phosphorylation through key signaling pathways. In examining the effects of the MEK/ERK1/2, PI3K/Akt, and calcium signaling pathways, we found that the MEK/ERK1/2 pathway and calcium do not regulate eNOS phosphorylation (peNOS), but the PI3K/Akt pathway, along with ACTH, regulates peNOS in LTH fetal adrenocortical cells (FACs); inhibition of the PI3K/Akt pathway resulted in reduced peNOS and enhanced cortisol production in response to ACTH in LTH FACs. Defining the regulatory role of these pathways will enhance our understanding of how these adaptations to LTH impact the fetus.
School of Medicine
Ducsay, Charles A.
Blood, Arlin B.
Myers, Dean A.
Pearce, William J.
Doctor of Philosophy (Medical Science)
Year Degree Awarded
Date (Title Page)
Library of Congress/MESH Subject Headings
Fetal Hypoxia; Adrenal Cortex -- physiopathology; Sheep -- Metabolism; Hydrocortisone -- Biosynthesis
Subject - Local
Cortisol Biosynthesis; Chronic Stress; Fetal Growth; Fetal Hypothalamo-pituitary-adrenal Axis; Endothelial Nitric Oxide Synthase
Loma Linda University Libraries
This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.
Newby, Elizabeth Anne, "Long-Term Hypoxia Alters Ovine Fetal Adrenal eNOS and Cortisol Biosynthesis" (2015). Loma Linda University Electronic Theses, Dissertations & Projects. 360.
Loma Linda University Electronic Theses and Dissertations
Loma Linda University. Del E. Webb Memorial Library. University Archives