Document Detail

Genomics of estradiol-3-sulfate action in the ovine fetal hypothalamus.
MedLine Citation:
PMID:  22570439     Owner:  NLM     Status:  MEDLINE    
In fetal sheep during late gestation sulfoconjugated estrogens in plasma reach a concentration 40-100 times greater than unconjugated estrogens. The objective of the present study was to determine the genomics of estradiol-3-sulfate (E(2)S) action in the ovine fetal brain. The hypothesis was that E(2)S stimulates genes involved in the neuroendocrine pathways that direct or facilitate fetal development at the end of gestation. Four sets of chronically catheterized ovine twin fetuses were studied (gestational age: 120-127 days gestation) with one infused with E(2)S intracerebroventricularly (1 mg/day) and the other remaining untreated (control). After euthanasia, mRNA samples were extracted from fetal brains. Only hypothalamic samples were employed for this study given the important function of this brain region in the control of the hypothalamus-pituitary-adrenal axis. Microarray analysis was performed following the Agilent protocol for one-color 8 × 15 microarrays, designed for Ovis aries. A total of 363 known genes were significantly upregulated by the E(2)S treatment (P < 0.05). Network and enrichment analyses were performed using the Cytoscape/Bingo software, and the results validated by quantitative real-time PCR. The main overrepresented biological processes resulting from this analysis were feeding behavior, hypoxia response, and transforming growth factor signaling. Notably, the genes involved in the feeding behavior (neuropeptide Y and agouti-related protein) were the most strongly induced by the E(2)S treatment. In conclusion, E(2)S may be an important component of the mechanism for activating orexigenic, hypoxia responsiveness and neuroprotective pathways in the lamb as it approaches postnatal life.
Maria Belen Rabaglino; Elaine Richards; Nancy Denslow; Maureen Keller-Wood; Charles E Wood
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-05-08
Journal Detail:
Title:  Physiological genomics     Volume:  44     ISSN:  1531-2267     ISO Abbreviation:  Physiol. Genomics     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-04     Completed Date:  2012-11-08     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  9815683     Medline TA:  Physiol Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  669-77     Citation Subset:  IM    
Department of Animal Sciences, University of Florida College of Agriculture and Life Sciences, Gainesville, Florida 32610-0274, USA.
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MeSH Terms
Estradiol / analogs & derivatives*,  pharmacology
Estrogens / pharmacology
Fetus / drug effects,  metabolism
Gestational Age
Hypothalamus / drug effects*,  metabolism*
Protein Array Analysis
RNA, Messenger / metabolism
Sheep / genetics*,  metabolism
Grant Support
Reg. No./Substance:
0/Estrogens; 0/RNA, Messenger; 4NKQ3751P6/estradiol-3-sulfate; 50-28-2/Estradiol

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