Thyroxine and testosterone transcriptionally regulate renin gene expression in the submaxillary gland of normal and transgenic mice carrying extra copies of the <i>Ren</i>2 gene

Tronik, Diana; Rougeon, François

doi:10.1016/0014-5793(88)80111-x

Cited by 28 publications

(15 citation statements)

References 23 publications

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“…Plasma renin concentration was 100-fold higher in mice with two renin genes than in those with one renin gene. In addition, Ren-2 has been found to be an androgen-responsive gene and is expected to be more activated in males than in females (13,38). In line with this notion, genetic deletion of the Ren-1 gene in 129/Sv mice produces hypotension in females but not in males (7), indicating involvement of Ren-2 in a sexually dimorphic mechanism in the control of blood pressure.…”

Section: Discussionmentioning

confidence: 89%

Influence of genetic background and gender on hypertension and renal failure in COX-2-deficient mice

Yang

Huang

et al. 2005

American Journal of Physiology-Renal Physiology

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Section: Discussionmentioning

confidence: 89%

Influence of genetic background and gender on hypertension and renal failure in COX-2-deficient mice

Yang

Huang

et al. 2005

American Journal of Physiology-Renal Physiology

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“…Several in vitro studies have shed further light on exactly how thyroid hormone may be influencing renin gene expression. For instance, in transgenic mice carrying extra copies of the Ren2 gene, thyroid hormone has been demonstrated to increase renin mRNA accumulation by directly stimulating transcription and/or stabilizing precursor renin mRNA (29,59). Additional studies using Calu-6 cells have confirmed that thyroid hormone directly stimulates the promoter region of the human renin gene through thyroid hormone response element-dependent mechanisms (36).…”

Section: Discussionmentioning

confidence: 99%

Thyroid hormone modulates renin and ANG II receptor expression in fetal sheep

Chen

Carey

Valego

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Fetal renin-angiotensin system (RAS) activity is developmentally regulated, increasing in late gestation toward term. At the same time, fetal hemodynamic parameters change, with blood pressure increasing and heart rate decreasing. During this period, fetal plasma thyroid hormone concentrations also increase significantly. In this study we utilized the technique of thyroidectomy (TX), which removes thyroid hormone from the circulation, to investigate the importance of thyroid hormone on the developmental changes in the RAS (in plasma, kidney, heart, and lung) and hemodynamic regulation in fetal sheep. TX was performed at 120 days of gestational age (dGA), and control fetuses were sham operated. Immediately before necropsy (ϳ137 dGA), fetuses were infused with isoproterenol and the hemodynamic responses were noted. TX significantly decreased plasma thyroid hormone concentrations and renal renin mRNA and renal active renin levels but did not change fetal plasma active renin levels. TX decreased both angiotensin II receptor subtype 1 (AT1) mRNA and protein levels in kidney and lung but not in the left ventricle. TX also was associated with increased ANG II receptor subtype 2 (AT2) mRNA and protein at the 44-kDa band in kidney, whereas AT2 protein was decreased at the 78-kDa level in kidney and lung tissue only. TX fetuses had significantly lower basal mean arterial blood pressures (MAP) and heart rates than controls. Isoproterenol infusion decreased MAP in TX fetuses. These findings support the hypothesis that thyroid hormone is important in modulating maturation of RAS and cardiovascular function in the late-gestation fetal sheep. renin-angiotensin system; fetus THE RENIN-ANGIOTENSIN SYSTEM (RAS), composed of renin, angiotensinogen, ANG I-converting enzyme (ACE), ANG II, and the ANG II receptor subtypes, plays an important role in regulating fetal growth and development, particularly with respect to the cardiovascular system, and electrolyte homeostatic mechanisms (2,22,48). It is well established that components of the fetal RAS are developmentally regulated and exhibit increased activity in late gestation (12,56,57,63). Changes in expression of the levels of ANG II receptor subtypes 1 and 2 (AT1 and AT2) are opposite, with AT1 mRNA low in early gestation and rising to a plateau later, before increasing rapidly close to term, whereas AT2 expression is highest during midpregnancy and then decreases gradually thereafter (46, 47). Tissue-dependent differences also are apparent (18,40,66). The mechanisms underlying these ontogenic patterns of expression are not clear.In fetal sheep, the changes in components of RAS activity appear temporally related to changes in thyroid hormone concentrations, which are low before 130 -135 days of gestational age (dGA) and then markedly increased toward parturition (19). A similar pattern of change is seen in humans (44). These observations suggest that thyroid hormone may be important in regulating ontogenic changes in renin and ANG II receptors.Thyroid hormone also exerts broad eff...

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“…It is conceivable that androgens modulate RAAS activity, thereby affecting blood pressure in a sex-specific manner and contributing to the hypertension observed in sGCα 1 -/-S6 mice (65). For example, renin 2 was reported to be an androgen-responsive gene (66,67). Moreover, overexpression of murine renin 2 in rats resulted in testosteronedependent hypertension (68).…”

Section: Figurementioning

confidence: 99%

Genetic modifiers of hypertension in soluble guanylate cyclase α1–deficient mice

Buys¹,

Raher²,

Kirby³

et al. 2012

J. Clin. Invest.

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Nitric oxide (NO) plays an essential role in regulating hypertension and blood flow by inducing relaxation of vascular smooth muscle. Male mice deficient in a NO receptor component, the α1 subunit of soluble guanylate cyclase (sGCα 1 ), are prone to hypertension in some, but not all, mouse strains, suggesting that additional genetic factors contribute to the onset of hypertension. Using linkage analyses, we discovered a quantitative trait locus (QTL) on chromosome 1 that was linked to mean arterial pressure (MAP) in the context of sGCα 1 deficiency. This region is syntenic with previously identified blood pressure-related QTLs in the human and rat genome and contains the genes coding for renin. Hypertension was associated with increased activity of the renin-angiotensin-aldosterone system (RAAS). Further, we found that RAAS inhibition normalized MAP and improved endothelium-dependent vasorelaxation in sGCα 1 -deficient mice. These data identify the RAAS as a blood pressure-modifying mechanism in a setting of impaired NO/cGMP signaling. IntroductionSystemic arterial hypertension is one of the most widespread public health problems in the developed world and the most prevalent modifiable risk factor for cardiovascular disease (CVD) in both women and men (1). The pathogenesis of essential hypertension is multifactorial, and in the vast majority of cases the etiology of hypertension is unknown. Although major advances in the treatment of hypertension have decreased CVD-related deaths over the last decade (2), many of the molecular mechanisms underlying the development of hypertension remain elusive. Genome-wide association studies (GWAS) suggest that there is a substantial heritable component to blood pressure (3, 4). Although GWAS have identified several loci associated with blood pressure in human beings, including loci containing genes that either regulate cGMP levels (4-7) or the renin-angiotensin-aldosterone system (RAAS) (8), many of the genetic factors determining blood pressure and how these factors interact remain to be identified.Renal abnormalities, such as decreased urinary sodium excretion in response to increasing renal perfusion pressure, and increased activity of the RAAS are generally considered to be a major contributor to the development of high blood pressure (9). However, other studies support the idea that hypertension can arise from primary vascular abnormalities (10, 11). The ability of NO to relax vascular smooth muscle and its essential role in the regulation of blood flow are well characterized (12, 13). Ample evidence suggests that altered NO signaling is involved in the pathogenesis of hypertension (14).One of the primary receptors for NO is soluble guanylate cyclase (sGC), a heme-containing enzyme that generates cGMP. The

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Thyroxine and testosterone transcriptionally regulate renin gene expression in the submaxillary gland of normal and transgenic mice carrying extra copies of the Ren2 gene

Cited by 28 publications

References 23 publications

Influence of genetic background and gender on hypertension and renal failure in COX-2-deficient mice

Influence of genetic background and gender on hypertension and renal failure in COX-2-deficient mice

Thyroid hormone modulates renin and ANG II receptor expression in fetal sheep

Genetic modifiers of hypertension in soluble guanylate cyclase α1–deficient mice

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