Abstract

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.

LLU Discipline

Physiology

Department

Basic Sciences

School

School of Medicine

First Advisor

Ducsay, Charles A.

Second Advisor

Blood, Arlin B.

Third Advisor

Myers, Dean A.

Fourth Advisor

Pearce, William J.

Fifth Advisor

Zhang, Lubo

Degree Name

Doctor of Philosophy (Medical Science)

Degree Level

Ph.D.

Year Degree Awarded

2015

Date (Title Page)

6-2015

Language

English

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

Type

Dissertation

Page Count

169

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

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.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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