Sex Hormones and Androgen Receptor: Risk Factors of Coronary Heart Disease in Elderly Men

Cao, Jian; Zou, Hui; Zhu, Bin; Wang, Hao; Li, Jian; Ding, Yu; Li, Xiaoying

doi:10.1016/s1001-9294(10)60019-3

Cited by 14 publications

(11 citation statements)

References 30 publications

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“…Likewise, the beneficial effect of androgens on the vascular function of males is widely recognized [5], [29]–[31]. The effects of androgenic derivatives on NO [12], [13] and prostanoids [32], [33] signalling pathways in different tissues have been described.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical studies have shown a correlation between hypotestosteronemia and incidence of cardiovascular diseases [5] and mortality risk [6]. These issues, as well as different mechanisms of action by which testosterone causes vasodilation were reviewed by Jones [7], In this regard, previous studies from our group have demonstrated an increase in the production of superoxide anion [8], prostanoids, such as thromboxane A 2 (TXA 2 ) [9], [10] and prostaglandin E 2 (PGE 2 ) [11] five months post-orchidectomy.…”

Section: Introductionmentioning

confidence: 99%

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Time-Dependent Effect of Orchidectomy on Vascular Nitric Oxide and Thromboxane A2 Release. Functional Implications to Control Cell Proliferation through Activation of the Epidermal Growth Factor Receptor

et al. 2014

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This study analyzes whether the release of nitric oxide (NO) and thromboxane A2 (TXA2) depends on the time lapsed since gonadal function is lost, and their correlation with the proliferation of vascular smooth muscle cells (VSMC) mediated by the epidermal growth factor receptor (EGFR). For this purpose, aortic and mesenteric artery segments from control and 6-weeks or 5-months orchidectomized rats were used to measure NO and TXA2 release. The results showed that the basal and acetylcholine (ACh)-induced NO release were decreased 6 weeks post-orchidectomy both in aorta and mesenteric artery, but were recovered 5 months thereafter up to levels similar to those found in arteries from control rats. The basal and ACh-induced TXA2 release increased in aorta and mesenteric artery 6 weeks post-orchidectomy, and was maintained at high levels 5 months thereafter. Since we previously observed that orchidectomy, which decreased testosterone level, enlarged the muscular layer of mesenteric arteries, the effect of testosterone on VSMC proliferation was analyzed. The results showed that treatment of cultured VSMC with testosterone downregulated mitogenic signaling pathways initiated by the ligand-dependent activation of the EGFR. In contrast, the EGFR pathways were constitutively active in mesenteric arteries of long-term orchidectomized rats. Thus, the exposure of mesenteric arteries from control rats to epidermal growth factor (EGF) induced the activation of EGFR signaling pathways. However, the addition of EGF to arteries from orchidectomized rats failed to induce a further activation of these pathways. In conclusion, this study shows that the release of NO depends on the time lapsed since the gonadal function is lost, while the release of TXA2 is already increased after short periods post-orchidectomy. The alterations in these signaling molecules could contribute to the constitutive activation of the EGFR and its downstream signaling pathways after long period post-orchidectomy enhancing the proliferation of the vascular muscular layer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Time-Dependent Effect of Orchidectomy on Vascular Nitric Oxide and Thromboxane A2 Release. Functional Implications to Control Cell Proliferation through Activation of the Epidermal Growth Factor Receptor

et al. 2014

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“…In this regard, we have demonstrated that the loss of gonadal function modifies the production of vasoconstrictor prostanoids [ 21 – 24 ], superoxide anion [ 25 – 27 ] and NO [ 28 ]. Since the number of vascular pathologies matching with decreased levels of sex hormones is increasing [ 29 , 30 ], it would be of interest investigate whether a DHA-supplemented diet could prevent vascular changes induced when an impaired gonadal function exist (i.e. : aging, hypogonadism, and pharmacological treatment of prostate cancer).…”

Section: Introductionmentioning

confidence: 99%

Effect of Dietary Docosahexaenoic Acid Supplementation on the Participation of Vasodilator Factors in Aorta from Orchidectomized Rats

et al. 2015

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Benefits of n-3 polyunsaturated fatty acids (PUFAs) against cardiovascular diseases have been reported. Vascular tone regulation is largely mediated by endothelial factors whose release is modulated by sex hormones. Since the incidence of cardiovascular pathologies has been correlated with decreased levels of sex hormones, the aim of this study was to analyze whether a diet supplemented with the specific PUFA docosahexaenoic acid (DHA) could prevent vascular changes induced by an impaired gonadal function. For this purpose, control and orchidectomized rats were fed with a standard diet supplemented with 5% (w/w) sunflower oil or with 3% (w/w) sunflower oil plus 2% (w/w) DHA. The lipid profile, the blood pressure, the production of prostanoids and nitric oxide (NO), and the redox status of biological samples from control and orchidectomized rats, fed control or DHA-supplemented diet, were analyzed. The vasodilator response and the contribution of NO, prostanoids and hyperpolarizing mechanisms were also studied. The results showed that orchidectomy negatively affected the lipid profile, increased the production of prostanoids and reactive oxygen species (ROS), and decreased NO production and the antioxidant capacity, as well as the participation of hyperpolarizing mechanisms in the vasodilator responses. The DHA-supplemented diet of the orchidectomized rats decreased the release of prostanoids and ROS, while increasing NO production and the antioxidant capacity, and it also improved the lipid profile. Additionally, it restored the participation of hyperpolarizing mechanisms by activating potassium. Since the modifications induced by the DHA-supplemented diet were observed in the orchidectomized, but not in the healthy group, DHA seems to exert cardioprotective effects in physiopathological situations in which vascular dysfunction exists.

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“…116 Men with CAD 105 Men with CAD had lower levels of FT than the control group. Low levels of FT are associated with the development of CAD.…”

Section: Resultsmentioning

confidence: 95%

Roles of Testosterone Replacement in Cardiac Ischemia–Reperfusion Injury

Pongkan¹,

Chattipakorn²

2015

J Cardiovasc Pharmacol Ther

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Testosterone is an anabolic steroid hormone, which is the major circulating androgen hormone in males. Testosterone levels decreasing below the normal physiological levels lead to a status known as androgen deficiency. Androgen deficiency has been shown to be a major risk factor in the development of several disorders, including obesity, metabolic syndrome, and ischemic heart disease. In the past decades, although several studies from animal models as well as clinical studies demonstrated that testosterone exerted cardioprotection, particularly during ischemia-reperfusion (I/R) injury, other preclinical and clinical studies have shown an inverse relationship between testosterone levels and cardioprotective effects. As a result, the effects of testosterone replacement on the heart remain controversial. In this review, reports regarding the roles of testosterone replacement in the heart following I/R injury are comprehensively summarized and discussed. At present, it may be concluded that chronic testosterone replacement at a physiological dose demonstrated cardioprotective effects, whereas acute testosterone replacement can cause adverse effects in the I/R heart.

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Sex Hormones and Androgen Receptor: Risk Factors of Coronary Heart Disease in Elderly Men

Abstract: Elderly male patients with CHD are found to have low levels of DHEAS, TT, FT, SHBG, and AR, while high concentrations of E2 and FSH. Low levels of TT and SHBG may be the potential risk factors of CHD in elderly men.

Cited by 14 publications

References 30 publications

Time-Dependent Effect of Orchidectomy on Vascular Nitric Oxide and Thromboxane A2 Release. Functional Implications to Control Cell Proliferation through Activation of the Epidermal Growth Factor Receptor

Time-Dependent Effect of Orchidectomy on Vascular Nitric Oxide and Thromboxane A2 Release. Functional Implications to Control Cell Proliferation through Activation of the Epidermal Growth Factor Receptor

Effect of Dietary Docosahexaenoic Acid Supplementation on the Participation of Vasodilator Factors in Aorta from Orchidectomized Rats

Roles of Testosterone Replacement in Cardiac Ischemia–Reperfusion Injury

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