Long-Term Hypoxia Alters Ovine Fetal Adrenal eNOS and Cortisol Biosynthesis

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy (Medical Science)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Basic Sciences

Year

2015

Author dc:creator

• Newby, Elizabeth Anne

Contributors dc:contributor

• Ducsay, Charles A.
• Blood, Arlin B.
• Myers, Dean A.
• Pearce, William J.
• Zhang, Lubo

• Medical Physiology
• Medical Sciences
• Medicine and Health Sciences
• Fetal Hypoxia; Adrenal Cortex -- physiopathology; Sheep -- Metabolism; Hydrocortisone -- Biosynthesis
• Cortisol Biosynthesis; Chronic Stress; Fetal Growth; Fetal Hypothalamo-pituitary-adrenal Axis; Endothelial Nitric Oxide Synthase

Statement dc: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.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/360

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-1355