Regulation of aldosterone secretion by mineralocorticoid receptor–mediated signaling

Chong, Cherish; Hamid, Anis; Yao, Tham M.; Garza, Amanda E; Pojoga, Luminita H.; Adler, Gail K.; Romero, José R.; Williams, Gordon H.

doi:10.1530/joe-16-0452

Cited by 28 publications

(25 citation statements)

References 36 publications

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“…Indeed, a number of in vitro and in vivo studies have shown that prior exposure of the adrenal gland to glucocorticoids results in a decreased response to ACTH. For example, CORT synthesis in response to ACTH is reduced in cultured adrenal cells treated with high levels of CORT or DEX (Carsia & Malamed, 1979 ; Chong et al., 2017 ; Peron, 1960 ). These findings are consistent with studies showing lower responses to ACTH in adrenals collected from hypophysectomized rats treated with CORT, when compared with adrenals from untreated rats (Langecker & Lurie, 1957 ).…”

Section: Regulation Of Corticosterone Synthesismentioning

confidence: 99%

Role of glucocorticoid negative feedback in the regulation of HPA axis pulsatility

Gjerstad

Lightman²,

Spiga³

2018

Stress

329

185

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The hypothalamic–pituitary–adrenal (HPA) axis is the major neuroendocrine axis regulating homeostasis in mammals. Glucocorticoid hormones are rapidly synthesized and secreted from the adrenal gland in response to stress. In addition, under basal conditions glucocorticoids are released rhythmically with both a circadian and an ultradian (pulsatile) pattern. These rhythms are important not only for normal function of glucocorticoid target organs, but also for the HPA axis responses to stress. Several studies have shown that disruption of glucocorticoid rhythms is associated with disease both in humans and in rodents. In this review, we will discuss our knowledge of the negative feedback mechanisms that regulate basal ultradian synthesis and secretion of glucocorticoids, including the role of glucocorticoid and mineralocorticoid receptors and their chaperone protein FKBP51. Moreover, in light of recent findings, we will also discuss the importance of intra-adrenal glucocorticoid receptor signaling in regulating glucocorticoid synthesis.

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Section: Regulation Of Corticosterone Synthesismentioning

confidence: 99%

Role of glucocorticoid negative feedback in the regulation of HPA axis pulsatility

Gjerstad

Lightman²,

Spiga³

2018

Stress

329

185

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“…Synthesis and release of Aldo, by the adrenal cortex, are promoted by the RAS and potassium ions (K + ) that are considered main triggering factors, as well as by minor stimulators like adrenocorticotropin (ACTH) and vasopressin (VP) [ 11 – 15 ]. Conversely, other molecules such as dopamine and atrial natriuretic peptide (ANP) exert an inhibitory effect on Aldo production/release [ 14 , 16 ].…”

Section: Aldosterone: From Biosynthesis To Releasementioning

confidence: 99%

Aldosterone and Mineralocorticoid Receptor System in Cardiovascular Physiology and Pathophysiology

Cannavò

Bencivenga²,

Liccardo³

et al. 2018

Oxidative Medicine and Cellular Longevity

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The mineralocorticoid hormone aldosterone (Aldo) has been intensively studied for its ability to influence both the physiology and pathophysiology of the cardiovascular system. Indeed, although research on Aldo actions for decades has mainly focused on its effects in the kidney, several lines of evidence have now demonstrated that this hormone exerts disparate extrarenal adverse effects, especially in the circulatory system. Accordingly, in the last lusters, a number of studies in preclinical models (in vitro and in vivo) and in humans have established that Aldo, following the interaction with its receptor—the mineralocorticoid receptor (MR)—is able to activate specific intracellular genomic and nongenomic pathways, thus regulating the homeostasis of the cardiovascular system. Importantly, through this mechanism of action, this hormone becomes a crucial regulator of the function and growth of different types of cells, including fibroblasts, cardiomyocytes, and vascular cells. For this main reason, it is plausible that when Aldo is present at high levels in the blood, it profoundly modifies the physiology of these cells, therefore being at the foundation of several cardiovascular disorders, such as heart failure (HF). On these grounds, in this review, we will provide an updated account on the current knowledge concerning Aldo activity in the cardiovascular system and the most recent preclinical studies and clinical trials designed to test better approaches able to counter the hyperactivity of the Aldo/MR signaling pathway in the setting of cardiovascular diseases.

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“…The biological processes underlying this self-inhibition are not known, but the glucocorticoid receptor (GR) is expressed in the adrenal cortex (15,18). Furthermore, the synthetic glucocorticoid dexamethasone-a specific GR agonist-has been shown to inhibit ACTH-induced corticosterone secretion from rat adrenocortical cells (19) as well as the transcription of steroidogenic genes through a mechanism that involves GRand SF-1-mediated induction of DAX-1 expression (20).…”

mentioning

confidence: 99%

Dynamic responses of the adrenal steroidogenic regulatory network

Spiga

Zavala

Walker

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The hypothalamic-pituitary-adrenal axis is a dynamic system regulating glucocorticoid hormone synthesis in the adrenal glands. Many key factors within the adrenal steroidogenic pathway have been identified and studied, but little is known about how these factors function collectively as a dynamic network of interacting components. To investigate this, we developed a mathematical model of the adrenal steroidogenic regulatory network that accounts for key regulatory processes occurring at different timescales. We used our model to predict the time evolution of steroidogenesis in response to physiological adrenocorticotropic hormone (ACTH) perturbations, ranging from basal pulses to larger stress-like stimulations (e.g., inflammatory stress). Testing these predictions experimentally in the rat, our results show that the steroidogenic regulatory network architecture is sufficient to respond to both small and large ACTH perturbations, but coupling this regulatory network with the immune pathway is necessary to explain the dissociated dynamics between ACTH and glucocorticoids observed under conditions of inflammatory stress. T he hypothalamic-pituitary-adrenal (HPA) axis is a stressresponsive neuroendocrine system that controls circulating levels of the vital glucocorticoid (CORT) hormones corticosterone (in rodents) and cortisol (in humans). These are steroids synthesized by the adrenal gland in response to stimulation by adrenocorticotropic hormone (ACTH), which is secreted by the anterior pituitary in response to corticotrophin-releasing hormone (CRH) and arginine vasopressin released from hypothalamic paraventricular neurons. These neurons receive circadian inputs from the suprachiasmatic nucleus and are activated in response to stress. Via the bloodstream, CORT accesses target tissues where it mediates metabolic, cognitive, and immune responses. CORT also regulates its own production through negative feedback inhibition of ACTH and CRH secretion from the pituitary and hypothalamus, respectively. To mount an effective response to stress, CORT must be secreted rapidly by the adrenal glands. However, because of its lipophilic nature, CORT cannot be prestored in vesicles and must therefore be rapidly synthesized de novo in response to ACTH stimulation.Under basal, unstressed conditions, ACTH and CORT exhibit ultradian oscillations. Although there is some evidence for pulsatility of CRH (1, 2), our recent work suggests that ACTH and CORT pulsatility is predominantly generated by a subhypothalamic oscillator within the pituitary-adrenal system (3, 4). The amplitude of these pulses varies in a circadian manner with larger pulses occurring at the start of the active phase (morning in humans, evening in rodents). Under normal physiological conditions, CORT secretion is tightly correlated with ACTH (5). However, there are a number of conditions where a dynamic dissociation between these hormones occurs (reviewed in ref. 6). For example, there is evidence that proinflammatory cytokines released during inflammation can poten...

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Regulation of aldosterone secretion by mineralocorticoid receptor–mediated signaling

Cited by 28 publications

References 36 publications

Role of glucocorticoid negative feedback in the regulation of HPA axis pulsatility

Role of glucocorticoid negative feedback in the regulation of HPA axis pulsatility

Aldosterone and Mineralocorticoid Receptor System in Cardiovascular Physiology and Pathophysiology

Dynamic responses of the adrenal steroidogenic regulatory network

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