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Endocrine Abstracts (2017) 49 OC5.5 | DOI: 10.1530/endoabs.49.OC5.5

ECE2017 Oral Communications Cardiovascular Endocrinology (5 abstracts)

Sex dimorphism of renal corticosteroid signaling during development and long term consequence on blood pressure

Laurence Dumeige 1 , Caroline Storey 1, , Lyvianne Decourtye 3 , Mélanie Nehlich 1, , Christophe Lhadj 1, , Say Viengchareun 1 , Laurent Kappeler 3 , Marc Lombès 1 & Laëtitia Martinerie 1,


1INSERM 1185, Le Kremlin Bicetre, France; 2Service d’endocrinologie pédiatrique, hôpital Robert Debré, APHP, Paris, France; 3INSERM UMR-S 938, Paris, France; 4Prem Up foundation, Paris, France.

Sex differences have been demonstrated in various biological processes such as arterial blood pressure. However, the potential sex dimorphism of the renin-angiotensin-aldosterone system and, by extension, the mineralocorticoid receptor (MR) signaling pathway, major regulators of blood pressure, has only been poorly studied, notably in 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 MR signaling were performed at different developmental stages in male and female mice using RT-qPCR, and were compared to that of the same genes in the lung, another mineralocorticoid epithelial target tissue. The potential role of sex hormones in the regulation of these genes was also investigated in differentiated KC3AC1 renal cells. Additionally, renal expression of the 11βHSD2 protein, a regulator of mineralocorticoid specificity, was measured by immunoblotting and its activity was indirectly assessed in the plasma using LC-MSMS method. SBP (91.7 ±1.1 vs 99.2 ±1.0 mmHg, P<0.0001) and HR (662 ±3 vs 687 ± 4 bpm, P<0.0001) were significantly lower in females compared to males. This was accompanied by a sex and tissue-specific expression of MR signaling pathway from fetal stage (E18) to adulthood, most notably for GR (Nr3c1) and Gilz renal mRNA expression which was twofold-lower in adult females mice compared to males (P<0.01). Moreover, 11βHSD2 mRNA and protein expression was found significantly increased in females (P<0.05), with a statistically different ratio of corticosterone/dehydrocorticosterone between both sexes (P=0.012). Finally, the implication of sex hormones in this sex-specific expression profile was confirmed in vitro, most notably for Gilz mRNA expression. We demonstrate a tissue-specific, sex-dependent and developmentally-regulated pattern of expression of MR signaling that could have important implications in physiology and pathology, particularly in the development of essential hypertension in men.

Volume 49

19th European Congress of Endocrinology

Lisbon, Portugal
20 May 2017 - 23 May 2017

European Society of Endocrinology 

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