Abstract

Our laboratory has demonstrated that sheep fetuses adapt to long-term hypoxia (LTH) by maintaining normal level of basal plasma cortisol despite increased adrenocorticotropic hormone (ACTH). But the mechanisms involved are not fully understood. Studies have shown that nitric oxide (NO) inhibits synthesis of steroid hormones in a variety of tissues, and in different animal species. Studies also showed that hypoxia increases both expression and activity levels of the nitric oxide (NO) generating enzyme, nitric oxide synthase (NOS), in certain tissues. We have here investigated the expression level and localization of NOS isoforms in sheep fetal adrenals. We also investigated the effects of NO on both basal and ACTH induced cortisol production. The studies in this dissertation have demonstrated that LTH increases NOS in adrenal cortex. Cortisol producing cells have been shown in these studies to express NOS. This study also showed that NO inhibits cortisol in the LTH fetuses. LTH increases NOS activity in sheep fetal adrenal cells not treated with ACTH. ACTH reduces NOS activity and increases sensitivity to NO in LTH fetal adrenal cells leading to increased cortisol production; a result similar to cortisol production observed during secondary stressor in vivo. The studies in this dissertation have demonstrated eNOS/NO as a mechanism involved in the maintenance of normal basal plasma cortisol in the face of increased basal plasma ACTH in the LTH sheep fetuses.

LLU Discipline

Physiology

Department

Physiology

School

Graduate Studies

First Advisor

Charles A. Ducsay

Second Advisor

William Pearce

Third Advisor

Dean Myers

Fourth Advisor

Steven M. Yellon

Fifth Advisor

Lubo Zhang

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2009

Date (Title Page)

3-2009

Language

English

Library of Congress/MESH Subject Headings

Fetal Hypoxia -- physiopathology; Pregnancy, Animal; Sheep; Adrenal Cortex -- physiology; Nitric Oxide -- metabolism; Nitric Oxide Synthase; Hydrocortisone -- antagonists and inhibitors; Adrenocorticotropic Hormone -- physiology; Enzyme Inhibitors -- pharmacology

Type

Dissertation

Page Count

xiii; 95

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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