The effects of estrogen and testosterone on gene expression in the rat mesenteric arteries

Eyster, Kathleen M.; Mark, Connie J.; Gayle, Richard; Martin, Douglas

doi:10.1016/j.vph.2007.06.007

Cited by 16 publications

(20 citation statements)

References 71 publications

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“…FIGLA is known to be a transcription factor that regulates other oocyte-specific genes (Bayne et al 2004; Huntriss et al 2002; Liang et al 1997). DBP is also a transcription factor whose expression has been shown to be induced by both estrogen and testosterone (Eyster et al 2007). DBP is known to regulate the expression levels of factor IX (Boccia et al 1996), which is an essential vitamin K-dependent serine protease that participates in the intrinsic pathway of coagulation.…”

Section: Discussionmentioning

confidence: 99%

Partial correlation network analyses to detect altered gene interactions in human disease: using preeclampsia as a model

et al. 2010

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Differences in gene expression between cases and controls have been identified for a number of human diseases. However, the underlying mechanisms of transcriptional regulation remain largely unknown. Beyond comparisons of absolute or relative expression levels, disease states may be associated with alterations in the observed correlational patterns among sets of genes. Here we use partial correlation networks aiming to compare the transcriptional co-regulation for 222 genes that are differentially expressed in decidual tissues between preeclampsia (PE) cases and non-PE controls. Partial correlation coefficients (PCCs) have been calculated in cases (N = 37) and controls (N = 58) separately. For all PCCs, we tested if they were significant non-zero in the cases and controls separately. In addition, to examine if a given PCC is different between the cases and controls, we tested if the difference between two PCCs were significant non-zero. In the group with PE cases, only five PCCs were significant (FDR p value ≤ 0.05), of which none were significantly different from the PCCs in the controls. However, in the controls we identified a total of 56 statistically significant PCCs (FDR p value ≤ 0.05), of which 31 were also significantly different (FDR p value ≤ 0.05) from the PCCs in the PE cases. The identified partial correlation networks included genes that are potentially relevant for developing PE, including both known susceptibility genes (EGFL7, HES1) and novel candidate genes (CFH, NADSYN1, DBP, FIGLA). Our results might suggest that disturbed interactions, or higher order relationships between these genes play an important role in developing the disease.

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Section: Discussionmentioning

confidence: 99%

Partial correlation network analyses to detect altered gene interactions in human disease: using preeclampsia as a model

et al. 2010

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“…ERs have been localized in human aorta, coronary, carotid, uterine and internal mammary artery, as well as umbilical vein [38]. In experimental animals, ERs have been identified in ovine uterine artery, rat aorta, mesenteric and carotid arteries, and mouse aorta [39, 40]. ERs have also been identified in veins of different species, but their responsiveness to estrogen has not been fully examined.…”

Section: Introductionmentioning

confidence: 99%

Vascular Effects of Estrogenic Menopausal Hormone Therapy

Reslan

Khalil²

2012

RRCT

100

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Cardiovascular disease (CVD) is more common in men and postmenopausal women (Post-MW) than premenopausal women (Pre-MW). Despite recent advances in preventive measures, the incidence of CVD in women has shown a rise that matched the increase in the Post-MW population. The increased incidence of CVD in Post-MW has been related to the decline in estrogen levels, and hence suggested vascular benefits of endogenous estrogen. Experimental studies have identified estrogen receptor ERα, ERβ and a novel estrogen binding membrane protein GPR30 (GPER) in blood vessels of humans and experimental animals. The interaction of estrogen with vascular ERs mediates both genomic and non-genomic effects. Estrogen promotes endothelium-dependent relaxation by increasing nitric oxide, prostacyclin, and hyperpolarizing factor. Estrogen also inhibits the mechanisms of vascular smooth muscle (VSM) contraction including [Ca2+]i, protein kinase C and Rho-kinase. Additional effects of estrogen on the vascular cytoskeleton, extracellular matrix, lipid profile and the vascular inflammatory response have been reported. In addition to the experimental evidence in animal models and vascular cells, initial observational studies in women using menopausal hormonal therapy (MHT) have suggested that estrogen may protect against CVD. However, randomized clinical trials (RCTs) such as the Heart and Estrogen/progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI), which examined the effects of conjugated equine estrogens (CEE) in older women with established CVD (HERS) or without overt CVD (WHI), failed to demonstrate protective vascular effects of estrogen treatment. Despite the initial set-back from the results of MHT RCTs, growing evidence now supports the ‘timing hypothesis’, which suggests that MHT could increase the risk of CVD if started late after menopause, but may produce beneficial cardiovascular effects in younger women during the perimenopausal period. The choice of an appropriate MHT dose, route of administration, and estrogen/progestin combination could maximize the vascular benefits of MHT and minimize other adverse effects, especially if given within a reasonably short time after menopause to women that seek MHT for the relief of menopausal symptoms.

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“…However, information regarding the global effects of different formulations of estrogens on arterial gene expression remains sparse. Work from our laboratory (Eyster et al, 2007; Rodrigo et al, 2003a; Rodrigo et al, 2003b) and others (Gao et al, 2006; Nakamura et al, 2004; Watanabe et al, 2004) have identified moderate effects of estrogen on gene expression in arterial tissue and cells.…”

Section: Introductionmentioning

confidence: 92%

Estrogens and selective estrogen receptor modulators regulate gene and protein expression in the mesenteric arteries

Mark-Kappeler¹,

Martin²,

Eyster³

2011

Vascular Pharmacology

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Estrogen has both beneficial and detrimental effects on the cardiovascular system. Selective estrogen receptor modulators (SERMs) exhibit partial estrogen agonist/antagonist activity in estrogen target tissues. Gene targets of estrogen and SERMs in the vasculature are not well-known. Thus, the present study tested the hypothesis that estrogens (ethinyl estradiol, estradiol benzoate, and equilin) and SERMs (tamoxifen and raloxifene) cause differential gene and protein expression in the vasculature. DNA microarray and real-time RT-PCR were used to investigate gene expression in the mesenteric arteries of estrogen and SERM treated ovariectomized rats. The genes shown to be differentially expressed included stearoyl-CoA desaturase (SCD), soluble epoxide hydrolase (sEH), secreted frizzled related protein-4 (SFRP-4), insulin-like growth factor-1 (IGF-1), phospholipase A2 group 1B (PLA2-G1B), and fatty acid synthase (FAS). Western blot further confirmed the differential expression of sEH, SFRP-4, FAS, and SCD protein. These results reveal that estrogens and SERMs cause differential gene and protein expression in the mesenteric artery. Consequently, the use of these agents may be associated with a unique profile of functional and structural changes in the mesenteric arterial circulation.

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The effects of estrogen and testosterone on gene expression in the rat mesenteric arteries

Cited by 16 publications

References 71 publications

Partial correlation network analyses to detect altered gene interactions in human disease: using preeclampsia as a model

Partial correlation network analyses to detect altered gene interactions in human disease: using preeclampsia as a model

Vascular Effects of Estrogenic Menopausal Hormone Therapy

Estrogens and selective estrogen receptor modulators regulate gene and protein expression in the mesenteric arteries

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