Mechanism of action of ACTH: Beyond cAMP

Gallo‐Payet, Nicole; Payet, M

doi:10.1002/jemt.10337

Cited by 110 publications

(83 citation statements)

References 145 publications

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“…One possibility includes a PRLinduced promotion of adrenal steroidogenesis. It is well known that ACTH regulates glucocorticoid secretion through the cyclic AMP (cAMP) pathway [31][32][33][34][35][36][37]. It has been shown that the action of PRL might be mediated through G-protein-adenylate cyclase coupling and cAMP production [38,39], where in chronic hyperprolactinemia enhances receptor-G-protein-adenylate cyclase coupling and cAMP production [2].…”

Section: Discussionmentioning

confidence: 99%

Physiological Roles of Prolactin in the Adrenocortical Response to Acute Restraint Stress

et al. 2007

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Abstract. The present study characterized the different hormonal responses to stress in the endocrine milieu with different circulating levels of prolactin (PRL) and examined the direct effects of PRL on adrenal steroidogenic responses to adrenocorticotropic hormone (ACTH) using experimentally induced hyperprolactinemia and hypoprolactinemia male rat models. Hyperprolactinemia was induced by transplantation of two adult female rat anterior pituitary glands under the kidney capsule for 2 weeks, and hypoprolactinemia was induced by daily subcutaneous injection of 2-Bromo-alphaErgocryptine (CB-154) for 2 weeks. Under stress conditions, the peak levels of ACTH were significantly higher in hypoprolactinemia than normal rats. Meanwhile, the peak levels of corticosterone and progesterone were significantly higher in hyperprolactinemia than in normal and hypoprolactinemia stressed rats. Results of in vitro experiments showed that adrenocortical cells in hyperprolactinemia exhibited higher basal levels of corticosterone and progesterone rats than normal and hypoprolactinemia rats. The stimulatory effect of ACTH on corticosterone and progesterone release was higher in hyperprolactinemia than hypoprolactinemia rats. In addition, PRL increased the stimulatory effect of ACTHinduced corticosterone secretion in all rat models. These results suggest that hypoprolactinemia and hyperprolactinemia rats exhibit marked differences in the response of their hypothalamic-pituitary-adrenal (HPA) axis during acute restrain stress. Additionally, these studies emphasize that the adrenal cortex might be more sensitive to ACTH stimulation in endocrine milieu with high levels of PRL resulting in high corticosterone and progesterone release.

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Section: Discussionmentioning

confidence: 99%

Physiological Roles of Prolactin in the Adrenocortical Response to Acute Restraint Stress

et al. 2007

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“…Although the regulation of aldosterone production by cAMP and Ca 2ϩ is summarized in recent reviews (19,37,46), the downstream signaling of both second messengers is controversial and far from being completely resolved. One of the reasons for controversial data may be connected with the fact that some of the signaling mechanisms generated by cAMP and Ca 2ϩ (activation of MAPKs, PKC, or small GTPases) may be more responsible for other cellular functions, such as proliferation or migration of ZG cells, than directly involved in acute stimulation of aldosterone production.…”

Section: Discussionmentioning

confidence: 99%

“…Many hormonal and paracrine factors are involved in the regulation of aldosterone production; however, under physiological conditions, the most important ones are adrenocorticotropin (ACTH), angiotensin II (ANG II), and extracellular K ϩ (19,46). The main action of ACTH in ZG cells is connected with the activation of transmembrane G s ␣-coupled ACTH receptors and the generation of cAMP as a second messenger (11,37).…”

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confidence: 99%

Regulation of aldosterone production from zona glomerulosa cells by ANG II and cAMP: evidence for PKA-independent activation of CaMK by cAMP

Gambaryan¹,

Butt²,

Tas³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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Aldosterone production in zona glomerulosa (ZG) cells of adrenal glands is regulated by various extracellular stimuli (K ϩ , ANG II, ACTH) that all converge on two major intracellular signaling pathways: an increase in cAMP production and calcium (Ca 2ϩ ) mobilization. However, molecular events downstream of the increase in intracellular cAMP and Ca 2ϩ content are controversial and far from being completely resolved. Here, we found that Ca 2ϩ /calmodulin-dependent protein kinases (CaMKs) play a predominant role in the regulation of aldosterone production stimulated by ANG II, ACTH, and cAMP. The specific CaMK inhibitor KN93 strongly reduced ANG II-, ACTH-, and cAMP-stimulated aldosterone production. In in vitro kinase assays and intact cells, we could show that cAMP-induced activation of CaMK, using the adenylate cyclase activator forskolin or the cAMP-analog Sp-5,6-DCIcBIMPS (cBIMPS), was not mediated by PKA. Activation of the recently identified cAMP target protein Epac (exchange protein directly activated by cAMP) by 8-pCPT-2Ј-O-Me-cAMP had no effect on CaMK activity and aldosterone production. Furthermore, we provide evidence that cAMP effects in ZG cells do not involve Ca 2ϩ or MAPK signaling. Our results suggest that ZG cells, in addition to PKA and Epac/Rap proteins, contain other as yet unidentified cAMP mediator(s) involved in regulating CaMK activity and aldosterone secretion. angiotension II; adenosine 3Ј,5Ј-cyclic monophosphate; adenosine 3Ј,5Ј-cyclic monophosphate-dependent protein kinase; Ca 2ϩ /calmodulin-dependent kinase ALL STEROID HORMONES, INCLUDING ALDOSTERONE, are synthesized from a common precursor, cholesterol. Stimulation of steroidproducing cells results in prompt mobilization of cholesterol esters from intracellular lipid droplets and their enzymatic hydrolysis to free cholesterol by cholesterol ester hydrolase (CEH) (8). Free cholesterol is then transported to the outer mitochondrial membrane (28,29,50,57), where it is transferred to the side-chain cleavage enzyme system that is localized at the inner mitochondrial membranes. The latter step is the rate-limiting step in steroidogenesis and depends on the activity and phosphorylation of the steroidogenic acute regulatory protein (StAR) (49).The steroid hormone aldosterone produced in adrenal zona glomeruloza (ZG) cells is a major regulator of intravascular volume and blood pressure. Many hormonal and paracrine factors are involved in the regulation of aldosterone production; however, under physiological conditions, the most important ones are adrenocorticotropin (ACTH), angiotensin II (ANG II), and extracellular K ϩ (19, 46). The main action of ACTH in ZG cells is connected with the activation of transmembrane G s ␣-coupled ACTH receptors and the generation of cAMP as a second messenger (11,37). Until the recent discovery of a new family of cAMP-binding proteins [exchange proteins directly activated by cAMP (Epacs)] that can directly activate small GTPases Rap1 and Rap2 (12), cAMP signaling was mainly linked to the activation of cAMP-de...

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“…ACTH as a key regulator of adrenal gland growth and function affects several intracellular signaling cascades which have been reviewed (Gallo-Payet & Payet 2003, Forti et al 2006, Otis et al 2007b) and which cannot be discussed here in a comprehensive manner. Concerning the effects of ACTH on ERK activation, positive (Le & Schimmer 2001, Ferreira et al 2004, McNeill et al 2005, weak (Lotfi et al 1997, Lepique et al 2000, negative ( Watanabe et al 1997), or no effects have been described (Cote et al 1998).…”

Section: Effectors Of Erk1/2 Activation In Adrenocortical Cellsmentioning

confidence: 99%

Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2

Hoeflich¹,

Bielohuby²

2008

Journal of Molecular Endocrinology

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The adrenal gland influences a multitude of processes during stress response, but also potently affects the immune system, glucose metabolism, electrolyte or water homeostasis, and cardiovascular functions. According to the present understanding, the adrenal cortex is tightly controlled by the hypothalamic-pituitary-adrenal axis. This axis involves hypothalamic CRH and pituitary ACTH which determine processes of adrenocortical growth and function. However, control of the adrenal gland comprises a plethora of additional endogenous or exogenous factors. Among those are diverse hormones, psychosocial parameters, physiological stress, secondary plant products, or even environmental pollutants. In the present review, we summarize the current view of endocrine growth control in the adrenal gland. We then discuss intracellular mechanisms of adrenal growth control and focus on extracellular signal regulated kinases 1/2 ( ERK1/2), which have been demonstrated to be controlled by not only ACTH or angiotensin II, but also by a large number of additional effectors. On the basis of these multiple exogenous or endogenous factors which impact on the adrenal gland through ERK1/2 activity, we speculate on a mechanism by which ERK1/2 act as a central integrative growth regulatory elements in the adrenal gland.

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Mechanism of action of ACTH: Beyond cAMP

Cited by 110 publications

References 145 publications

Physiological Roles of Prolactin in the Adrenocortical Response to Acute Restraint Stress

Physiological Roles of Prolactin in the Adrenocortical Response to Acute Restraint Stress

Regulation of aldosterone production from zona glomerulosa cells by ANG II and cAMP: evidence for PKA-independent activation of CaMK by cAMP

Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2

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