Research article summary (published 9 Aug 2005):

Long-term hypoxia represses the expression of key genes regulating cortisol biosynthesis in the near-term ovine fetus.

Full Abstract

Basal plasma ACTH(1-39) concentrations are elevated in long-term hypoxic (LTH) fetal sheep. This study was designed to determine whether the expression of genes regulating cortisol biosynthesis was altered after LTH. Pregnant ewes were maintained at high altitude (3,820 m) from day 30 of gestation to near term, when the animals were transported to the laboratory. Reduced PO2 was maintained by nitrogen infusion through a maternal tracheal catheter. On days 137-141, fetal adrenal glands were collected from LTH and normoxic control fetuses. Real-time PCR was used to quantify mRNA for steroidogenic acute regulatory protein, 17alpha-hydroxylase (CYP17), 21-hydroxylase (CYP21), cholesterol side-chain cleavage (CYP11A1), 3beta-hydroxysteroid dehydrogenase type II (HSD3B2), and the ACTH receptor. We analyzed mRNA by slot-blot hybridization and also quantified mRNA for transcription factors necessary for adrenocortical development by quantitative real-time PCR: steroidogenic factor 1 and dosage-sensitive sex reversal, adrenal hypoplasia congenital, critical region on the X chromosome (DAX-1). Protein was quantified by Western blot analysis. Adrenal mRNAs for CYP17, CYP11A1, and the ACTH receptor were significantly reduced in LTH fetal sheep compared with levels shown in controls. Similarly, CYP11A1 protein and CYP17 protein were reduced in the LTH group. CYP21, steroidogenic acute regulatory protein, HSD3B2, steroidogenic factor 1, and DAX-1 expressions were not altered in response to LTH. We conclude that expression of two key steroidogenic enzymes (CYP17, CYP11A1) regulating cortisol biosynthesis and the ACTH receptor is lower in response to LTH. This likely represents an adaptive response to LTH, to prevent excessive cortisol production that would restrict fetal growth and potentially induce preterm delivery.

Author information

Author/s: Myers, Dean A (DA); Hyatt, Kimberly (K); Mlynarczyk, Malgorzata (M); Bird, Ian M (IM); Ducsay, Charles A (CA);

Affiliation: Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.

Grants: HD-31226 (Agency:NICHD NIH HHS) ; HD-33147 (Agency:NICHD NIH HHS) ; MH-60728 (Agency:NIMH NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol), published in United States. (Language: eng)

Reference: 2005-Dec; vol 289 (issue 6) : pp R1707-14

Dates: Created 2005/11/09; Completed 2006/01/10; Revised 2007/11/14;

PMID: 16099825, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Adrenal Glands - embryology; metabolism Animals Anoxia - embryology; metabolism Cholesterol Side-Chain Cleavage Enzyme - metabolism Chronic Disease

Gene Expression Regulation, Developmental Hydrocortisone - biosynthesis Phosphoproteins - metabolism Sheep Steroid 17-alpha-Hydroxylase - metabolism

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Phosphoproteins (0) ; steroidogenic acute regulatory protein (0) ; Hydrocortisone (50-23-7) ; Cholesterol Side-Chain Cleavage Enzyme (EC 1.14.15.6) ; Steroid 17-alpha-Hydroxylase (EC 1.14.99.9)

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