Journal article
Dehydroepiandrosterone Stimulates Endothelial Proliferation and Angiogenesis through Extracellular Signal-Regulated Kinase 1/2-Mediated Mechanisms
Endocrinology (Philadelphia), Vol.149(3), pp.889-898
03/01/2008
DOI: 10.1210/en.2007-1125
PMCID: PMC2275364
PMID: 18079198
Abstract
Dehydroepiandrosterone (DHEA) activates a plasma membrane receptor on vascular endothelial cells and phosphorylates ERK 1/2. We hypothesize that ERK1/2-dependent vascular endothelial proliferation underlies part of the beneficial vascular effect of DHEA. DHEA (0.1–10 nm) activated ERK1/2 in bovine aortic endothelial cells (BAECs) by 15 min, causing nuclear translocation of phosphorylated ERK1/2 and phosphorylation of nuclear p90 ribosomal S6 kinase. ERK1/2 phosphorylation was dependent on plasma membrane-initiated activation of Gi/o proteins and the upstream MAPK kinase because the effect was seen with albumin-conjugated DHEA and was blocked by pertussis toxin or PD098059. A 15-min incubation of BAECs with 1 nm DHEA (or albumin-conjugated DHEA) increased endothelial proliferation by 30% at 24 h. This effect was not altered by inhibition of estrogen or androgen receptors or nitric oxide production. There was a similar effect of DHEA to increase endothelial migration. DHEA also increased the formation of primitive capillary tubes of BAECs in vitro in solubilized basement membrane. These rapid DHEA-induced effects were reversed by the inhibition of either Gi/o-proteins or ERK1/2. Additionally, DHEA enhanced angiogenesis in vivo in a chick embryo chorioallantoic membrane assay. These findings indicate that exposure to DHEA, at concentrations found in human blood, causes vascular endothelial proliferation by a plasma membrane-initiated activity that is Gi/o and ERK1/2 dependent. These data, along with previous findings, define an important vascular endothelial cell signaling pathway that is activated by DHEA and suggest that this steroid may play a role in vascular function.
Details
- Title: Subtitle
- Dehydroepiandrosterone Stimulates Endothelial Proliferation and Angiogenesis through Extracellular Signal-Regulated Kinase 1/2-Mediated Mechanisms
- Creators
- Dongmin Liu - Division of Endocrinology (D.L., M.I., L.L.H., J.S.D.), Veterans Affairs Medical Center, and Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Mary Iruthayanathan - Division of Endocrinology (D.L., M.I., L.L.H., J.S.D.), Veterans Affairs Medical Center, and Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Laurie L Homan - Division of Endocrinology (D.L., M.I., L.L.H., J.S.D.), Veterans Affairs Medical Center, and Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Yiqiang Wang - The Shandong Provincial Key Laboratory of Ophthalmology (Yi.W., L.Y., Ya.W.), Shandong Eye Institute, 266071 Qingdao, ChinaLingling Yang - The Shandong Provincial Key Laboratory of Ophthalmology (Yi.W., L.Y., Ya.W.), Shandong Eye Institute, 266071 Qingdao, ChinaYao Wang - The Shandong Provincial Key Laboratory of Ophthalmology (Yi.W., L.Y., Ya.W.), Shandong Eye Institute, 266071 Qingdao, ChinaJoseph S Dillon - Division of Endocrinology (D.L., M.I., L.L.H., J.S.D.), Veterans Affairs Medical Center, and Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Endocrinology (Philadelphia), Vol.149(3), pp.889-898
- DOI
- 10.1210/en.2007-1125
- PMID
- 18079198
- PMCID
- PMC2275364
- ISSN
- 0013-7227
- eISSN
- 1945-7170
- Language
- English
- Date published
- 03/01/2008
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094643902771
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