Low TRH-TSH Responses in Human Essential Hypertension

Lupi, S.; Lutzky, C. A.; Yampey, E. W. De; Finkielman, S.; Nahmod, Víctor E.

doi:10.3109/10641968809033899

Cited by 3 publications

(3 citation statements)

References 15 publications

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“…6,7 It was thus tempting to speculate that the component genes of the TRH system may be associated with essential hypertension. Because Lupi et al 9 reported that hypertensive patients have a blunted TSH response to TRH, indicating that there is a possible defect in the TRHR activation-mediated TSH release, we postulated that TRHR may be also involved in essential hypertension. Accordingly, we searched for molecular variants of the TRHR gene promoter.…”

Section: Discussionmentioning

confidence: 99%

“…Many endocrine disorders arise from mutations of these receptors, which result in changes of their basal or ligand-induced activity. 8 In this regard, Lupi et al 9 have demonstrated that hypertensive patients have a blunted TSH response to intravenous TRH bolus injection, suggesting a defect in the TRHR activationmediated TSH release. In summary, we postulated that the TRHR gene is involved in human hypertension.…”

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confidence: 99%

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Thyrotropin-Releasing Hormone Receptor (TRHR) Gene Is Associated With Essential Hypertension

et al. 2001

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Abstract-In essential hypertension, a polygenic and multifactorial syndrome, several genes interact with the environment to produce high blood pressure. Thyrotropin-releasing hormone (TRH) plays an important role in central cardiovascular regulation. We have described that TRH overexpression induces hypertension in a normal rat, which was reversed by TRH antisense treatment. This treatment also reduces the central TRH hyperactivity in spontaneously hypertensive rats and normalizes blood pressure. Human TRH receptor (TRHR) belongs to the G protein-coupled seven-transmembrane domain receptor superfamily. Mutations of these receptors may result in constitutive activation. As it has been demonstrated that hypertensive patients have a blunted TSH response to TRH injection, suggesting a defect in the TRHR, we postulate that the TRHR gene is involved in human hypertension. We studied 2 independent populations from different geographic regions of our country: a sample of adult subjects from a referral clinic and a population-based sample of high school students. In search of molecular variants of TRHR, we disclosed that a polymorphic TG dinucleotide repeat (STR) at Ϫ68 bp and a novel single nucleotide polymorphism, a G3 C conversion at Ϫ221 located in the promoter of the TRHR are associated with essential hypertension. As STRs detected in gene promoters are potential Z-DNA-forming sequences and seem to affect gene expression, we studied the potentially different transcriptional activity of these TRHR promoter variants and found that the S/Ϫ221C allele has a higher affinity than does the L/GϪ221 allele to nuclear protein factor(s Key Words: epidemiology Ⅲ genes Ⅲ hypertension, essential Ⅲ hormone Ⅲ thyroliberin Ⅲ receptor T hyrotropin-releasing hormone (TRH), a small neuropeptide (p-Glu-His-Pro-NH 2 ) initially identified in the hypothalamus, which stimulates the synthesis and secretion of thyroid-stimulating hormone (TSH) and prolactin, 1 was shown to be amply distributed in the central nervous system. 2 TRH participates in central cardiovascular regulation, producing dose-dependent pressor effects. 3 We have reported that central overexpression of the TRH precursor in normal rats induces a long-lasting elevation of arterial blood pressure along with an increase in the diencephalic TRH content in a dose-dependent manner. These effects were specifically reversed by an antisense treatment. 4 In addition, spontaneously hypertensive rats (SHR) show a supersensitivity to the hypertensive effects of exogenous TRH 5 and present a pre-and postsynaptic hyperactivity of the extrahypothalamic TRH system. 6 . Accordingly, we also recently reported that a specific intracerebroventricular antisense treatment against the initiation translation codon region of the TRH precursor gene diminished both effects, the augmented TRH content and the increased systolic blood pressure, in a dose-dependent manner, independent of the thyroid status. 7 These results indicated that the central TRH system participates in the development or maintenance...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Thyrotropin-Releasing Hormone Receptor (TRHR) Gene Is Associated With Essential Hypertension

et al. 2001

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“…As seen in several neuroendocrine diseases, mutations of these receptors may result in constitutive activation. Since it has been demonstrated that hypertensive patients have a blunted TSH response to TRH injection suggesting a defect in the hTRH-R [55], we postulated that the hTRH-R gene is involved in essential hypertension. We studied two independent populations from different geographic regions of our country, a sample of adult subjects from a referral clinic and a population-based sample of high school students.…”

Section: Extrahypothalamic Trh In Human Hypertensionmentioning

confidence: 97%