Influence of gender and sex hormones on 5α-dihydrotestosterone elicited effect in isolated left atria of rats: Role of β-adrenoceptors and ornithine decarboxylase activity

Bordallo, Javier; Secades, Lorena; Bordallo, Carmen; Cantabrana, Begoña; Sánchez, Manuel

doi:10.1016/j.ejphar.2008.12.019

Cited by 9 publications

(5 citation statements)

References 63 publications

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“…Our findings are consistent with a report that ␤-adrenergic receptor protein expression in the rat ventricle does not differ in males and females, as determined by both immunoblotting (5) and radioligand binding (7). However, this contrasts with other reports that males have greater ␤-adrenergic receptor density in rat left ventricular membranes (2,28). Our results suggest that the sex differences in response to ␤-adrenergic receptor stimulation are not because of differences in ␤-adrenergic receptor expression.…”

Section: ␤-Adrenergic Contractile Responsesupporting

confidence: 90%

“…Few studies have investigated sex differences in cardiac ␤-ad-renergic receptor function, and the results of these studies have been inconsistent. Controversy exists as to whether sex differences are present in ␤-adrenergic receptor function (5,18,23,28), as well as expression (2,4,7,28). However, none of these functional studies were performed in intact myocardium.…”

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confidence: 99%

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Sex differences and the effects of ovariectomy on the β-adrenergic contractile response

McIntosh

Chandrasekera

Lasley

2011

American Journal of Physiology-Heart and Circulatory Physiology

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The presence of sex differences in myocardial β-adrenergic responsiveness is controversial, and limited studies have addressed the mechanism underlying these differences. Studies were performed using isolated perfused hearts from male, intact female and ovariectomized female mice to investigate sex differences and the effects of ovarian hormone withdrawal on β-adrenergic receptor function. Female hearts exhibited blunted contractile responses to the β-adrenergic receptor agonist isoproterenol (ISO) compared with males but not ovariectomized females. There were no sex differences in β(1)-adrenergic receptor gene or protein expression. To investigate the role of adenylyl cyclase, phosphodiesterase, and the cAMP-signaling cascade in generating sex differences in the β-adrenergic contractile response, dose-response studies were performed in isolated perfused male and female hearts using forskolin, 3-isobutyl-1-methylxanthine (IBMX), and 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate (CPT-cAMP). Males showed a modestly enhanced contractile response to forskolin at 300 nM and 5 μM compared with females, but there were no sex differences in the response to IBMX or CPT-cAMP. The role of the A(1) adenosine receptor (A(1)AR) in antagonizing the β-adrenergic contractile response was investigated using both the A(1)AR agonist 2-chloro-N(6)-cyclopentyl-adenosine and A(1)AR knockout (KO) mice. Intact females showed an enhanced A(1)AR anti-adrenergic effect compared with males and ovariectomized females. The β-adrenergic contractile response was potentiated in both male and female A(1)ARKO hearts, with sex differences no longer present above 1 nM ISO. The β-adrenergic contractile response is greater in male hearts than females, and minor differences in the action of adenylyl cyclase or the A(1)AR may contribute to these sex differences.

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Section: ␤-Adrenergic Contractile Responsesupporting

confidence: 90%

mentioning

confidence: 99%

Sex differences and the effects of ovariectomy on the β-adrenergic contractile response

McIntosh

Chandrasekera

Lasley

2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…Ornithine, metabolized by X-chromosome-encoded ornithine transcarbamylase, had a significant gender interaction. A divergent effect of androgens on ornithine decarboxylase activity in rat hearts has been reported before 64 , but to our knowledge we are the first to report ornithine's interaction with gender in human heart failure myocardium. TMAO was significantly elevated in male heart failure myocardium only, consistent with its metabolism by gender-specific flavin-containing monooxygenases 65 .…”

Section: Discussionmentioning

confidence: 63%

Core functional nodes and sex-specific pathways in human ischaemic and dilated cardiomyopathy

Parker

Pearson

et al. 2020

Nat Commun

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Poor access to human left ventricular myocardium is a significant limitation in the study of heart failure (HF). Here, we utilise a carefully procured large human heart biobank of cryopreserved left ventricular myocardium to obtain direct molecular insights into ischaemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), the most common causes of HF worldwide. We perform unbiased, deep proteomic and metabolomic analyses of 51 left ventricular (LV) samples from 44 cryopreserved human ICM and DCM hearts, compared to age-, gender-, and BMI-matched, histopathologically normal, donor controls. We report a dramatic reduction in serum amyloid A1 protein in ICM hearts, perturbed thyroid hormone signalling pathways and significant reductions in oxidoreductase co-factor riboflavin-5monophosphate and glycolytic intermediate fructose-6-phosphate in both; unveil genderspecific changes in HF, including nitric oxide-related arginine metabolism, mitochondrial substrates, and X chromosome-linked protein and metabolite changes; and provide an interactive online application as a publicly-available resource.

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“…Alternatively, these differences could also indicate the possibility that a DNA-binding-independent AR signaling pathway acts in concert with the classical genomic pathway in the heart to promote cardiac growth and development. This latter hypothesis is supported by the fact that rapid androgen signaling pathways have been identified in cardiomyocytes in vitro (Vicencio et al 2006), and a recent study has showed that DHT treatment of isolated rat left atria causes a non-transcriptional cardiotonic response associated with increased ornithine decarboxylase (ODC) activity (Bordallo et al 2009). The fact that there was no difference in absolute or relative heart mass between ARKO males and control females indicates that the sex differences in cardiac mass are determined solely by androgens acting through the genomic AR pathway in males.…”

Section: Discussionmentioning

confidence: 68%

DNA-binding-dependent androgen receptor signaling contributes to gender differences and has physiological actions in males and females

MacLean¹,

Moore²,

Sastra³

et al. 2010

Journal of Endocrinology

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We used our genomic androgen receptor (AR) knockout (ARKO) mouse model, in which the AR is unable to bind DNA to: 1) document gender differences between males and females; 2) identify the genomic (DNA-binding-dependent) AR-mediated actions in males; 3) determine the contribution of genomic AR-mediated actions to these gender differences; and 4) identify physiological genomic AR-mediated actions in females. At 9 weeks of age, control males had higher body, heart and kidney mass, lower spleen mass, and longer and larger bones compared to control females. Compared to control males, ARKO males had lower body and kidney mass, higher splenic mass, and reductions in cortical and trabecular bone. Deletion of the AR in ARKO males abolished the gender differences in heart and cortical bone.Compared with control females, ARKO females had normal body weight, but 14% lower heart mass and heart weight/ body weight ratio. Relative kidney mass was also reduced, and relative spleen mass was increased. ARKO females had a significant reduction in cortical bone growth and changes in trabecular architecture, although with no net change in trabecular bone volume. In conclusion, we have shown that androgens acting via the genomic AR signaling pathway mediate, at least in part, the gender differences in body mass, heart, kidney, spleen, and bone, and play a physiological role in the regulation of cardiac, kidney and splenic size, cortical bone growth, and trabecular bone architecture in females.

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Influence of gender and sex hormones on 5α-dihydrotestosterone elicited effect in isolated left atria of rats: Role of β-adrenoceptors and ornithine decarboxylase activity

Cited by 9 publications

References 63 publications

Sex differences and the effects of ovariectomy on the β-adrenergic contractile response

Sex differences and the effects of ovariectomy on the β-adrenergic contractile response

Core functional nodes and sex-specific pathways in human ischaemic and dilated cardiomyopathy

DNA-binding-dependent androgen receptor signaling contributes to gender differences and has physiological actions in males and females

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