The neuropeptide substance P regulates aldosterone secretion in human adrenals

Wils, Julien; Duparc, Céline; Cailleux, Anne-Françoise; Lopez, Antoine-Guy; Guiheneuf, C.; Boutelet, Isabelle; Boyer, Hadrien-Gaël; Dubessy, Christophe; Cherifi, Saloua; Cauliez, Bruno; Gobet, Françoise; Defortescu, G.; Ménard, Jean-François; Louiset, Estelle; Lefebvre, Henri

doi:10.1038/s41467-020-16470-8

Cited by 24 publications

(16 citation statements)

References 41 publications

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“…KaNDy Therapeutics demonstrated that elinzanetant is effective in the treatment of VMS in a phase II trial [80]. The potent action of elinzanetant on NK1 receptors is posited to bring some benefit with regard to peripheral flushing and sleep in VMS [80], whereas the alternate effects of NK1 antagonists on centrally mediated emesis and addiction circuits [26,27], gastrointestinal pharmacology [28], and the hypothalamic-pituitary-adrenal axis [81] is of unknown consequence in menopausal women. Additional clinical testing will further characterize the NK1R/NK3R pharmacology of elinzanetant.…”

Section: Expert Opinionmentioning

confidence: 99%

Fezolinetant in the treatment of vasomotor symptoms associated with menopause

Depypere

Lademacher

Siddiqui

et al. 2021

Expert Opinion on Investigational Drugs

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Introduction: Although international clinical practice guidelines recognize a continued role for menopausal hormone therapy (HT), particularly for symptomatic women <60 years of age or within 10 years of menopause, safety and tolerability concerns have discouraged HT use due to potential links with a perceived increased risk of hormone-dependent cancers, and an established risk of stroke and venous thromboembolism. There is therefore a need for safe, effective non-hormonal therapy for relief of menopausal vasomotor symptoms (VMS).Areas covered: This narrative review summarizes the dataset accrued for fezolinetant, a neurokinin-3 receptor (NK3R) antagonist in clinical development for menopause-associated VMS. Expert opinion: Altered signaling in neuroendocrine circuits at menopause leads to VMS wherein NK3R activity plays a key role to modulate the thermoregulatory center in a manner conducive to triggering the 'hot flash' response. Thus, a new generation of NK3R antagonists has entered clinical development to specifically target the mechanistic basis of VMS. Fezolinetant is the most advanced NK3R antagonist in terms of stage of clinical development. Results to date have demonstrated rapid and substantial reduction in VMS frequency and severity and associated improvements in health-related quality of life. NK3R antagonists offer a non-hormonal alternative to HT for the treatment of menopause-related VMS.

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Section: Expert Opinionmentioning

confidence: 99%

Fezolinetant in the treatment of vasomotor symptoms associated with menopause

Depypere

Lademacher

Siddiqui

et al. 2021

Expert Opinion on Investigational Drugs

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“…Continuous monitoring of cortisol levels, one of the indicators of chronic stress, the potential cause of various diseases, can greatly help to prevent chronic diseases. [148,162] To continuously monitor cortisol secreted from the adrenal glands in terms of stress, Sunwoo et al demonstrated that a flexible probe inserted into the adrenal gland could measure electrophysiological signals correlated with cellular activity (Figure 8b). [9] This developed probe was fabricated by patterning metal electrodes of Au and Cr on a polyimide (PI) substrate, which has been shown to be biocompatible.…”

Section: Functional E-drugs For Chronic Diseasesmentioning

confidence: 99%

Electronic Drugs: Spatial and Temporal Medical Treatment of Human Diseases

et al. 2021

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pharmaceutical drug delivery and healthcare systems. E-drugs are biocompatible electronic devices capable of identifying specific biological analytes (e.g., glucose, enzymes, and other biomolecules), [1,2] environmental stimuli (e.g., strain, pressure, and external temperature), and electrophysiological signals (e.g., electrocardiograms (ECG), electromyograms (EMG), and electroencephalography (EEG)) to monitor health status and deliver therapeutic treatments in a controlled manner via wireless prompts. [3][4][5] Owing to their innovative functions and technologies, e-drugs have been widely adopted in pharmaceutical and medical research to monitor and treat chronic diseases, which are still considered difficult to cure. Conventional pharmaceutical treatments or medical procedures for chronic diseases encounter a major obstacle in patient compliance, as they involve regular drug intake or treatments. [6] For example, patients with diabetes are recommended to collect blood samples to measure their glucose levels twice a day. However, the International Diabetes Management Practice Study reported that only 29.7-38.5% of patients with type-2 diabetes in Asia, Eastern Europe, and Latin America self-monitor their glucose levels, which hinders effective management of their condition. [7] As a strategy to improve patients' adherence to drug intake and treatments, electronic devices capable of continuously monitoring biological signal levels and therapeutic response via wireless applications have been demanded by the markets.The fundamental differences between electronics and biological tissues have emerged as a challenge in the development of an advanced generation of e-drugs. For instance, soft biological tissues have a low modulus of elasticity, which is typically less than 100 kPa, and high moisture content. By contrast, conventional electronics are generally made of electronic materials such as metals and silicone, which are stiff, with modulus greater than 80 GPa, dry, and static. [8] This mechanical and physical mismatch between human tissues and electronics causes adverse clinical outcomes. Major consequences include inflammatory responses induced by the micromotion of the implant, during and after implantation, as well as scar tissue and fibrotic encapsulation, which substantially compromises the performance and lifetime of e-drugs. [9,10] Recent advances in diagnostics and medicines emphasize the spatial and temporal aspects of monitoring and treating diseases. However, conventional therapeutics, including oral administration and injection, have difficulties meeting these aspects due to physiological and technological limitations, such as long-term implantation and a narrow therapeutic window. As an innovative approach to overcome these limitations, electronic devices known as electronic drugs (e-drugs) have been developed to monitor real-time body signals and deliver specific treatments to targeted tissues or organs. For example, ingestible and patch-type e-drugs could detect changes in biomarkers at the target s...

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“…Aldosterone biosynthesis in the ZG is physiologically regulated by Angiotensin II (Ang II), potassium (K + ), and at a lesser extent by the AdrenoCorticoTropic Hormone (ACTH). Other bioactive compounds (serotonin, leptin, endothelin, nitric oxide, catecholamines, atrial natriuretic peptide, neuropeptide substance P) released by adipocytes, mast cells, chromaffin cells, or nerve ending located close to ZG cells were also shown to stimulate aldosterone secretion [ 3 , 4 ]. Stimulation of the Renin–Angiotensin System (RAS) is initiated by increased sympathetic activity, reduced perfusion pressure in the renal afferent arterioles, or decreased sodium content in the macula densa of the renal distal tubules, which lead to the release of renin from juxtaglomerular cells.…”

Section: Mineralocorticoid Signaling Pathwaymentioning

confidence: 99%

Sexual Dimorphism of Corticosteroid Signaling during Kidney Development

Laulhé

Dumeige

et al. 2021

IJMS

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Sexual dimorphism involves differences between biological sexes that go beyond sexual characteristics. In mammals, differences between sexes have been demonstrated regarding various biological processes, including blood pressure and predisposition to develop hypertension early in adulthood, which may rely on early events during development and in the neonatal period. Recent studies suggest that corticosteroid signaling pathways (comprising glucocorticoid and mineralocorticoid signaling pathways) have distinct tissue-specific expression and regulation during this specific temporal window in a sex-dependent manner, most notably in the kidney. This review outlines the evidence for a gender differential expression and activation of renal corticosteroid signaling pathways in the mammalian fetus and neonate, from mouse to human, that may favor mineralocorticoid signaling in females and glucocorticoid signaling in males. Determining the effects of such differences may shed light on short term and long term pathophysiological consequences, markedly for males.

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The neuropeptide substance P regulates aldosterone secretion in human adrenals

Cited by 24 publications

References 41 publications

Fezolinetant in the treatment of vasomotor symptoms associated with menopause

Fezolinetant in the treatment of vasomotor symptoms associated with menopause

Electronic Drugs: Spatial and Temporal Medical Treatment of Human Diseases

Sexual Dimorphism of Corticosteroid Signaling during Kidney Development

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