Sex-Specificity of Mineralocorticoid Target Gene Expression during Renal Development, and Long-Term Consequences
Sex differences have been identified in various biological processes, including hypertension. The mineralocorticoid signaling pathway is an important contributor to early arterial hypertension, however its sex-specific expression has been scarcely studied, particularly with respect to the kidney. Ba...
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doaj-7fe981aa1e3949c3890180b3d973d1dd2020-11-24T21:44:40ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-02-0118245710.3390/ijms18020457ijms18020457Sex-Specificity of Mineralocorticoid Target Gene Expression during Renal Development, and Long-Term ConsequencesLaurence Dumeige0Caroline Storey1Lyvianne Decourtye2Melanie Nehlich3Christophe Lhadj4Say Viengchareun5Laurent Kappeler6Marc Lombès7Laetitia Martinerie8Inserm U1185, Univ Paris Sud, Université Paris-Saclay, F-94276 Le Kremlin-Bicêtre, FranceInserm U1185, Univ Paris Sud, Université Paris-Saclay, F-94276 Le Kremlin-Bicêtre, FranceInserm, UMR_S938, Centre de Recherche Saint-Antoine, F-75012 Paris, FranceInserm U1185, Univ Paris Sud, Université Paris-Saclay, F-94276 Le Kremlin-Bicêtre, FranceInserm U1185, Univ Paris Sud, Université Paris-Saclay, F-94276 Le Kremlin-Bicêtre, FranceInserm U1185, Univ Paris Sud, Université Paris-Saclay, F-94276 Le Kremlin-Bicêtre, FranceInserm, UMR_S938, Centre de Recherche Saint-Antoine, F-75012 Paris, FranceInserm U1185, Univ Paris Sud, Université Paris-Saclay, F-94276 Le Kremlin-Bicêtre, FranceInserm U1185, Univ Paris Sud, Université Paris-Saclay, F-94276 Le Kremlin-Bicêtre, FranceSex differences have been identified in various biological processes, including hypertension. The mineralocorticoid signaling pathway is an important contributor to early arterial hypertension, however its sex-specific expression has been scarcely studied, particularly with respect to the kidney. Basal systolic blood pressure (SBP) and heart rate (HR) were measured in adult male and female mice. Renal gene expression studies of major players of mineralocorticoid signaling were performed at different developmental stages in male and female mice using reverse transcription quantitative PCR (RT-qPCR), and were compared to those of the same genes in the lung, another mineralocorticoid epithelial target tissue that regulates ion exchange and electrolyte balance. The role of sex hormones in the regulation of these genes was also investigated in differentiated KC3AC1 renal cells. Additionally, renal expression of the 11 β-hydroxysteroid dehydrogenase type 2 (11βHSD2) protein, a regulator of mineralocorticoid specificity, was measured by immunoblotting and its activity was indirectly assessed in the plasma using liquid-chromatography coupled to mass spectrometry in tandem (LC-MSMS) method. SBP and HR were found to be significantly lower in females compared to males. This was accompanied by a sex- and tissue-specific expression profile throughout renal development of the mineralocorticoid target genes serum and glucocorticoid-regulated kinase 1 (Sgk1) and glucocorticoid-induced leucine zipper protein (Gilz), together with Hsd11b2, Finally, the implication of sex hormones in this sex-specific expression profile was demonstrated in vitro, most notably for Gilz mRNA expression. We demonstrate a tissue-specific, sex-dependent and developmentally-regulated pattern of expression of the mineralocorticoid pathway that could have important implications in physiology and pathology.http://www.mdpi.com/1422-0067/18/2/457mineralocorticoid signaling pathwaysexual dimorphismgene expressionhypertension |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laurence Dumeige Caroline Storey Lyvianne Decourtye Melanie Nehlich Christophe Lhadj Say Viengchareun Laurent Kappeler Marc Lombès Laetitia Martinerie |
spellingShingle |
Laurence Dumeige Caroline Storey Lyvianne Decourtye Melanie Nehlich Christophe Lhadj Say Viengchareun Laurent Kappeler Marc Lombès Laetitia Martinerie Sex-Specificity of Mineralocorticoid Target Gene Expression during Renal Development, and Long-Term Consequences International Journal of Molecular Sciences mineralocorticoid signaling pathway sexual dimorphism gene expression hypertension |
author_facet |
Laurence Dumeige Caroline Storey Lyvianne Decourtye Melanie Nehlich Christophe Lhadj Say Viengchareun Laurent Kappeler Marc Lombès Laetitia Martinerie |
author_sort |
Laurence Dumeige |
title |
Sex-Specificity of Mineralocorticoid Target Gene Expression during Renal Development, and Long-Term Consequences |
title_short |
Sex-Specificity of Mineralocorticoid Target Gene Expression during Renal Development, and Long-Term Consequences |
title_full |
Sex-Specificity of Mineralocorticoid Target Gene Expression during Renal Development, and Long-Term Consequences |
title_fullStr |
Sex-Specificity of Mineralocorticoid Target Gene Expression during Renal Development, and Long-Term Consequences |
title_full_unstemmed |
Sex-Specificity of Mineralocorticoid Target Gene Expression during Renal Development, and Long-Term Consequences |
title_sort |
sex-specificity of mineralocorticoid target gene expression during renal development, and long-term consequences |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2017-02-01 |
description |
Sex differences have been identified in various biological processes, including hypertension. The mineralocorticoid signaling pathway is an important contributor to early arterial hypertension, however its sex-specific expression has been scarcely studied, particularly with respect to the kidney. Basal systolic blood pressure (SBP) and heart rate (HR) were measured in adult male and female mice. Renal gene expression studies of major players of mineralocorticoid signaling were performed at different developmental stages in male and female mice using reverse transcription quantitative PCR (RT-qPCR), and were compared to those of the same genes in the lung, another mineralocorticoid epithelial target tissue that regulates ion exchange and electrolyte balance. The role of sex hormones in the regulation of these genes was also investigated in differentiated KC3AC1 renal cells. Additionally, renal expression of the 11 β-hydroxysteroid dehydrogenase type 2 (11βHSD2) protein, a regulator of mineralocorticoid specificity, was measured by immunoblotting and its activity was indirectly assessed in the plasma using liquid-chromatography coupled to mass spectrometry in tandem (LC-MSMS) method. SBP and HR were found to be significantly lower in females compared to males. This was accompanied by a sex- and tissue-specific expression profile throughout renal development of the mineralocorticoid target genes serum and glucocorticoid-regulated kinase 1 (Sgk1) and glucocorticoid-induced leucine zipper protein (Gilz), together with Hsd11b2, Finally, the implication of sex hormones in this sex-specific expression profile was demonstrated in vitro, most notably for Gilz mRNA expression. We demonstrate a tissue-specific, sex-dependent and developmentally-regulated pattern of expression of the mineralocorticoid pathway that could have important implications in physiology and pathology. |
topic |
mineralocorticoid signaling pathway sexual dimorphism gene expression hypertension |
url |
http://www.mdpi.com/1422-0067/18/2/457 |
work_keys_str_mv |
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