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Contribution à l'étude de l'effet de la substance P sur la sécrétion d'aldostérone dans la glande surrénale humaine normale

Abstract : Aldosterone secretion by the adrenal gland is principally under control of the circulating renin-angiotensin system (RAS) and kalemia. Aldosterone synthesis is also influenced by intra-adrenal paracrine factors including neuropeptides. Especially, tachykinins, like substance P (SP), can be released by nerve endings in the adrenal cortex. The role of SP in the regulation of the adrenal function has been evaluated in animals but only scarcely investigated in humans. The aim of the present study is to explore the role of SP in the control of mineralocorticoid synthesis in the human adrenal gland. In vitro experiments conducted in normal adrenal samples reveal expression of the TAC1 encoding SP which is detected by immunohistochemistry in non adrenergic non cholinergic nerve fibres in the zona glomerulosa. SP-positive fibres establish close contacts with aldosterone-producing cells which express the SP receptor, i.e. the NK1 receptor (NK1R). SP stimulates aldosterone production from cultured adrenocortical cells, an effect which is inhibited by the NK1R antagonist aprepitant. The action of SP is mediated by the ERK pathway and involves upregulation of several genes encoding steroidogenic enzymes. The physiological role of SP in the regulation of aldosterone secretion was further assessed through a prospective clinical placebo-controlled trial investigating the impact of aprepitant on plasma and urine aldosterone levels in healthy volunteers. Aprepitant reduced daily aldosterone production and plasma aldosterone concentration (PAC) in recumbency but did not modify PAC in upright position. These data show that SP exerts a stimulatory tone on aldosterone production in man.
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Submitted on : Friday, July 3, 2020 - 11:52:20 AM
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  • HAL Id : tel-02888765, version 1


Julien Wils. Contribution à l'étude de l'effet de la substance P sur la sécrétion d'aldostérone dans la glande surrénale humaine normale. Endocrinologie et métabolisme. Normandie Université, 2018. Français. ⟨NNT : 2018NORMR011⟩. ⟨tel-02888765⟩



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