Dihydrotestosterone and estradiol-17β mutually neutralize their inhibitory effects on human vascular smooth muscle cell growth in vitro

Sömjen, Dalia; Kohen, Förtüne; Gayer, Batya; Knoll, Esther; Many, Ariel; Stern, Naftali

doi:10.1016/j.jsbmb.2008.11.014

Cited by 4 publications

(5 citation statements)

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“…Experiments on animals point to the effect of the DHT level on reduction of cardiovascular risk [28,29]. Experiments with cell lines provide proof of the effect of the high DHT level inhibiting the growth of vessel smooth muscular cells in cell culture; this inhibition is dose dependant [30]. Exogenous DHT delivery to human macrophage cell culture is proatherogenic [31].…”

Section: Discussionmentioning

confidence: 98%

The differences between aromatizable and non-aromatizable androgens in relation to body composition and metabolic syndrome risk factors in men

Pospíšilová

Vaňková

Hill

et al. 2012

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Discussionmentioning

confidence: 98%

The differences between aromatizable and non-aromatizable androgens in relation to body composition and metabolic syndrome risk factors in men

Pospíšilová

Vaňková

Hill

et al. 2012

The Journal of Steroid Biochemistry and Molecular Biology

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“…Furthermore, the DHT-dependent increases in COX-2 could be blocked with the classical AR antagonist bicalutamide. The DHT concentration (10 nM) used in this study is well within the range of DHT concentrations (1-400 nM) used in previous studies of the effects of DHT on inflammation in human endothelial cells (8,24,27) and the range of DHT concentrations (3-300 nM) used to examine the effects of DHT on human vascular smooth muscle cell proliferation (32). Although a lower concentration of DHT (0.1 nM) has been shown to reduce vascular inflammation, as measured by VCAM and COX-2 levels in human vein endothelial cells (27), data for vascular smooth muscle cells had previously been lacking.…”

Section: Discussionmentioning

confidence: 99%

“…Although much of the work regarding androgens and vascular inflammation has been conducted in endothelial cells (8,16,24,25,27), there are few reports of the effects of androgens on inflammation in vascular smooth muscle (32).…”

mentioning

confidence: 99%

Dihydrotestosterone alters cyclooxygenase-2 levels in human coronary artery smooth muscle cells

Osterlund

Gonzales

2010

American Journal of Physiology-Endocrinology and Metabolism

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Osterlund KL, Handa RJ, Gonzales RJ. Dihydrotestosterone alters cyclooxygenase-2 levels in human coronary artery smooth muscle cells. Am J Physiol Endocrinol Metab 298: E838 -E845, 2010. First published January 26, 2010; doi:10.1152/ajpendo.00693.2009.-Both protective and nonprotective effects of androgens on the cardiovascular system have been reported. Our previous studies show that the potent androgen receptor (AR) agonist dihydrotestosterone (DHT) increases levels of the vascular inflammatory mediator cyclooxygenase (COX)-2 in rodent cerebral arteries independent of an inflammatory stimulus. Little is known about the effects of androgens on inflammation in human vascular tissues. Therefore, we tested the hypothesis that DHT alters COX-2 levels in the absence and presence of induced inflammation in primary human coronary artery smooth muscle cells (HCASMC). Furthermore, we tested the ancillary hypothesis that DHT's effects on COX-2 levels are AR-dependent. Cells were treated with DHT (10 nM) or vehicle for 6 h in the presence or absence of LPS or IL-1␤. Similar to previous observations in rodent arteries, in HCASMC, DHT alone increased COX-2 levels compared with vehicle. This effect of DHT was attenuated in the presence of the AR antagonist bicalutamide. Conversely, in the presence of LPS or IL-1␤, increases in COX-2 were attenuated by cotreatment with DHT. Bicalutamide did not affect this response, suggesting that DHTinduced decreases in COX-2 levels occur independent of AR stimulation. Thus we conclude that DHT differentially influences COX-2 levels under physiological and pathophysiological conditions in HCASMC. This effect of DHT on COX-2 involves AR-dependent andindependent mechanisms, depending on the physiological state of the cell. vascular smooth muscle; interleukin-1␤; lipopolysaccharide; inflammation; androgen PRECLINICAL AND CLINICAL RESEARCH suggests that vascular inflammation is a critical regulator in the etiology and progression of cardiovascular disease that, if not treated or managed, can eventually lead to fatal clinical end points, such as stroke and myocardial infarction. Clinical data consistently show that cardiovascular disease is more prevalent in men than in premenopausal women (39). Numerous studies have focused on the role of estrogens in contributing to the sex-related disparities in cardiovascular disease, but the cardiovascular actions of androgens are not well understood. Among the few documented studies, there is disagreement as to whether androgens exacerbate or beneficially contribute to the development and progression of cardiovascular disease. Because chronic vascular inflammation contributes significantly to the pathogenesis of cardiovascular diseases (13,31,37), it is important to investigate the role of androgens under normal and pathophysiological conditions.During vascular inflammation, monocytes and macrophages penetrate the vessel wall and produce inflammatory cytokines (34), such as interleukin-1␤ (IL-1␤), leading to activation of NF-B, a transcription factor for i...

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“…The doses for the sex steroids were chosen because they had previously been investigated using dose-response curves by members of the same laboratory group ( 23 , 24 ) and were in line with those reported in vascular tissue in the recent scientific literature ( 25 , 26 ). Importantly, a literature review before the experiments beginning suggested that higher doses of estrogen and dihydrotestosterone (DHT) in particular could inhibit VSMC proliferation and action ( 27 ).…”

Section: Methodsmentioning

confidence: 99%

Effects of Sex Hormones on Vascular Reactivity in Boys With Hypospadias

Lucas-Herald,

Montezano,

Alves-Lopes

et al. 2023

The Journal of Clinical Endocrinology &Amp; Metabolism

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Background Arteries from boys with hypospadias demonstrate hypercontractility and impaired vasorelaxation. The role of sex hormones in these responses in unclear. Aims We compared effects of sex steroids on vascular reactivity in healthy boys and boys with hypospadias. Methods Excess foreskin tissue was obtained from 11 boys undergoing hypospadias repair (cases) and 12 undergoing routine circumcision (controls) (median age (range) 1.5 (1.2, 2.7) yrs) and small resistance arteries were isolated. Vessels were mounted on wire myographs and vascular reactivity was assessed in the absence/presence of 17β-estradiol, dihydrotestosterone (DHT) and testosterone. Results In controls, testosterone and 17β-estradiol increased contraction (Emax: 83.74 basal vs 125.4 after testosterone, p < 0.0002 and 83.74 vs 110.2 after estradiol, p = 0.02). 17β-estradiol reduced vasorelaxation in arteries from controls (Emax: 10.6 vs 15.6 to acetylcholine (ACh), p < 0.0001 and Emax: 14.6 vs 20.5 to sodium nitroprusside (SNP), p < 0.0001). In hypospadias, testosterone (Emax: 137.9 vs 107.2, p = 0.01) and 17β-estradiol (Emax: 156.9 vs 23.6, p < 0.0001) reduced contraction. Androgens, but not 17β-estradiol, increased endothelium-dependent and endothelium-independent vasorelaxation in cases (Emax: 77.3 vs 51.7 with testosterone, p = 0.02 and vs 48.2 with DHT to ACh, p = 0.0001; Emax: 43.0 vs 39.5 with testosterone, p = 0.02 and vs 39.6 vs 37.5 with DHT to SNP, p = 0.04). Conclusion In healthy boys, testosterone and 17β-estradiol promote a vasoconstrictor phenotype whereas in boys with hypospadias, these sex hormones reduce vasoconstriction, with androgens promoting vasorelaxation. Differences in baseline artery function may therefore be sex hormone independent and the impact of early-life variations in androgen exposure on vascular function needs further study.

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Dihydrotestosterone and estradiol-17β mutually neutralize their inhibitory effects on human vascular smooth muscle cell growth in vitro

Cited by 4 publications

References 28 publications

The differences between aromatizable and non-aromatizable androgens in relation to body composition and metabolic syndrome risk factors in men

The differences between aromatizable and non-aromatizable androgens in relation to body composition and metabolic syndrome risk factors in men

Dihydrotestosterone alters cyclooxygenase-2 levels in human coronary artery smooth muscle cells

Effects of Sex Hormones on Vascular Reactivity in Boys With Hypospadias

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