| Dihydrotestosterone Attenuates Hypoxia Inducible Factor-1alpha and Cyclooxygenase-2 in Cerebral Arteries during Hypoxia or Hypoxia with Glucose Deprivation. | |
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MedLine Citation:
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PMID: 21856910 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Dihydrotestosterone (DHT) attenuates cytokine-induced cyclooxygenase-2 (COX-2) in coronary vascular smooth muscle. Since hypoxia inducible factor-1alpha (HIF-1α) activation can lead to COX-2 production, this study determined the influence of DHT on HIF-1α and COX-2 following hypoxia or hypoxia with glucose deprivation (HGD) in the cerebral vasculature. COX-2 and HIF-1α levels were assessed via western blot and HIF-1α activation was indirectly measured via a DNA binding assay. Experiments were performed using cerebral arteries isolated from castrated male rats treated in vivo with placebo or DHT (18 days) followed by hypoxic exposure ex vivo (1% O2), cerebral arteries isolated from castrated male rats treated ex vivo with vehicle or DHT (10 or 100 nM; 6 h) then exposed to hypoxia ex vivo (1% O2), or primary human brain vascular smooth muscle cells treated with DHT (10 nM; 6 h) or vehicle then exposed to hypoxia or HGD. Under normoxic conditions, DHT increased COX-2 (Cells 51%; arteries ex vivo 31%; arteries in vivo 161%) but had no effect on HIF-1α. Following hypoxia or HGD, HIF-1α and COX-2 levels were increased; this response was blunted by DHT (Cells HGD: -47% COX-2, -34% HIF-1α; Cells hypoxia: -29% COX-2, -54% HIF-1α; arteries ex vivo: -37% COX-2; arteries in vivo: -35% COX-2) and not reversed by androgen receptor blockade. Hypoxia-induced HIF-1α DNA-binding was also attenuated by DHT (arteries ex vivo and in vivo: -55%). These results demonstrate that upregulation of COX-2 and HIF-1α in response to hypoxia is suppressed by DHT via an androgen receptor independent mechanism. |
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Authors:
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Kristen L Zuloaga; Rayna J Gonzales |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-19 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: - ISSN: 1522-1539 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1University of Arizona-Phoenix. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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