Find results with:

Add another field

Search by date

to

Searching collections:

Loma Linda University Electronic Theses and Dissertations

Add or remove collections

Home Page 1

Reference URL

Share

Add tags

Comment

Rate

To link to the entire object, paste this link in email, IM or document

To embed the entire object, paste this HTML in website

To link to this page, paste this link in email, IM or document

To embed this page, paste this HTML in website

Long-Term Hypoxia Regulates Cortisol Biosynthesis in the Ovine Fetal Adrenal Cortex

you wish to report:

Your comment:

Your Name:

Submit

Cancel

...

Back to top

Powered by CONTENTdm®

Rating
Title	Long-Term Hypoxia Regulates Cortisol Biosynthesis in the Ovine Fetal Adrenal Cortex
Author	Vargas, Vladimir Enrique
Abstract	Previous studies demonstrated enhanced fetal adrenal cortisol biosynthesis following exposure to long-term hypoxia (LTH). The studies presented here were designed to determine the mechanism(s) regulating this important adaptive endocrine response. Ewes were maintained at high altitude (3,820 m) from approximately day 40 to 138-141 of gestation. Fetal adrenal glands were then collected from LTH and age matched normoxic controls. Dispersed fetal adrenal cortical cells (FACs) were untreated, treated with ACTH, treated in combination with ACTH precursors (POMC and 22-kDa pro-ACTH), or pre-treated with H-89 and or UO126 followed by ACTH treatment. Following ACTH treatment, cortisol biosynthesis increased in both groups but values were significantly higher in the LTH FACs. Neither basal nor ACTH-stimulated cAMP levels differed between groups. H-89 inhibition of PKA decreased cortisol to levels observed in the un-stimulated FACs in both groups. StAR protein was higher in the LTH group under un-stimulated and following ACTH treatment. ACTH precursors alone or in combination with ACTH did not affect cortisol synthesis in either group. StAR mRNA was not different between groups. Although UO126 inhibition of ERK decreased cortisol in both groups, the net decrease was greater in the LTH group in response to ACTH treatment. Basal ERK1/2, and pERK1/2 were not different between groups. In response to ACTH treatment pERK1/2 was higher in the LTH FACs, however, pERK1/2 declined significantly in normoxic control but not LTH FACs. Total ERK1/2 did not differ between groups or after ACTH treatment. UO126 significantly reduced pERK 10 to 20 fold in both groups similarly at all time points. Together with previous in vivo data, these data indicate that enhanced cortisol output in the LTH group is the result of increased adrenal ACTH sensitivity. This enhanced sensitivity is not due to differences in cAMP, PKA and or ACTH precursors. StAR, and the ERKs appear to play a key role in the enhanced cortisol response to ACTH following LTH. These adaptive responses to LTH are critical in maintaining normal fetal growth and development and these data may have important clinical implications.
Discipline	Physiology
Department	Basic Sciences
School	School of Medicine
Advisor	Ducsay, Charles A.
Degree Name	Doctor of Philosophy
Degree Level	Ph.D.
Year Degree Awarded	2010
Date (Title Page)	2010-12
Language	English
Subject - LCSH	Endocrinology Endocrine glands
Subject - Local	Fetal adrenal cortisol biosynthesis; Hypoxia; Adaptive endocrine response; Biosynthesis; Fetal physiology
Type	Dissertation
Page count	136 p.
Digital format	Application/PDF
Digital Publisher	Loma Linda University Libraries
Copyright	Author
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.
Citation Information	To cite the digital version, include its Reference URL, found by following the link in the gray header above the digital file.
Collection	Loma Linda University Electronic Theses & Dissertations
Collection Website	http://archives.llu.edu/colls/lludis
Repository	Loma Linda University. Del E. Webb Memorial Library. University Archives

Find results with:

Searching collections:

Home Page 1

Long-Term Hypoxia Regulates Cortisol Biosynthesis in the Ovine Fetal Adrenal Cortex

Object Description

Description

Tags

Comments

Long-Term Hypoxia Regulates Cortisol Biosynthesis in the...

Long-Term Hypoxia Regulates Cortisol Biosynthesis in the...

	All
	Pages Enter page numbers or page ranges separated by commas. For example: 1,3,5-12