| LEPTIN RECEPTOR ANTAGONIST TREATMENT AMELIORATES THE EFFECTS OF LONG-TERM MATERNAL HYPOXIA ON ADRENAL EXPRESSION OF KEY STEROIDOGENIC GENES IN THE OVINE FETUS. | |
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MedLine Citation:
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PMID: 23344230 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We previously reported elevated adipose leptin expression, plasma leptin concentrations and adrenocortical leptin receptor expression in the long term hypoxic (LTH) ovine fetus. This study addressed if leptin antagonist (LA) administration to LTH fetal sheep altered expression of key genes governing cortisol synthesis. Ewes were maintained at high altitude (3,820 m) from 40-130 days gestation (dG), returned to Loma Linda University and implanted with a maternal tracheal catheter. Reduced PO(2) was maintained by nitrogen infusion. On 132 dG, LTH (n=11) and age-matched, normoxic control (n=11) fetuses underwent vascular catheter implantation. At 138 dG, fetuses were continuously infused with either saline or the LA (1.5mg/kg/day) for four days and samples collected for blood gasses, ACTH and cortisol. Fetal adrenal cortex was collected for determination of StAR, ACTH and leptin receptor, CYP11A1, CYP11B1, CYP17, CYP21, STAT3, pSTAT3 and HSD3B expression. In the saline infused LTH fetuses, StAR, ACTH receptor, CYP11A1 and CYP17 expression was significantly lower compared to control (p<0.05) while levels of CYP11B1, CYP21 and HSD3B mRNA were similar between groups. LA infusion restored expression of StAR, pSTAT3, CYP11A1 and CYP17 but not ACTH receptor to normal ontogenic levels in the LTH group while having no effect on control fetuses. Neither fetal plasma ACTH nor cortisol concentrations were altered by LA infusion. We speculate that while leptin plays a role in governing expression of key enzymes and StAR in response to LTH, other factors play a role in modulating cortisol synthesis in these fetuses. |
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Authors:
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Charles A Ducsay; Ken Furuta; Vladimir E Vargas; Kanchan M Kaushal; Krista Singleton; Kimberly Hyatt; Dean A Myers |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-23 |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: - ISSN: 1522-1490 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Loma Linda University. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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