Document Detail


Leptin receptor antagonist treatment ameliorates the effects of long-term maternal hypoxia on adrenal expression of key steroidogenic genes in the ovine fetus.
MedLine Citation:
PMID:  23344230     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 whether leptin antagonist (LA) administration to LTH fetal sheep altered expression of key genes governing cortisol synthesis. Ewes were maintained at high altitude (3,820 meters) from 40 to 130 days gestation (dG), returned to Loma Linda University, and implanted with a maternal tracheal catheter. Reduced Po2 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 (1.5 mg·kg(-1)·day(-1)) for 4 days and samples collected for blood gases, ACTH, and cortisol. Fetal adrenal cortex was collected for determination of steriodogenic acute regulatory protein (StAR), ACTH, and leptin receptor, cholesterol side-chain cleavage (CYP11A1), cytochrome P-450 11β-hydroxylase (CYP11B1), 17α-hydroxylase (CYP17), 21-hydroxylase (CYP21), signal transducer and activator of transcription 3 (STAT3), pSTAT3, and 17β-hydroxysteroid dehydrogenase (HSD3B) expression. In the saline-infused LTH fetuses, StAR, ACTH receptor, CYP11A1, and CYP17 expression was significantly lower compared with control (P < 0.05), whereas 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.
Authors:
Charles A Ducsay; Ken Furuta; Vladimir E Vargas; Kanchan M Kaushal; Krista Singleton; Kimberly Hyatt; Dean A Myers
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-23
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  304     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-18     Completed Date:  2013-05-08     Revised Date:  2014-03-26    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R435-42     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
17-Hydroxysteroid Dehydrogenases / metabolism
Adrenal Cortex / drug effects,  metabolism*
Animals
Anoxia / genetics*,  metabolism
Female
Fetus / metabolism*
Gene Expression Regulation / drug effects*
Gestational Age
Hydrocortisone / biosynthesis*
Leptin / metabolism
Receptors, Corticotropin / metabolism
Receptors, Leptin / antagonists & inhibitors*
Sheep
Steroid 21-Hydroxylase / metabolism
Time Factors
Grant Support
ID/Acronym/Agency:
P01HD-31226/HD/NICHD NIH HHS; R01HD-51951/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Leptin; 0/Receptors, Corticotropin; 0/Receptors, Leptin; EC 1.1.-/17-Hydroxysteroid Dehydrogenases; EC 1.1.1.51/3 (or 17)-beta-hydroxysteroid dehydrogenase; EC 1.14.99.10/Steroid 21-Hydroxylase; WI4X0X7BPJ/Hydrocortisone
Comments/Corrections

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