Regulation of corticotropin receptor number and messenger RNA in cultured human adrenocortical cells by corticotropin and angiotensin II.

Lebrethon, Marie-Christine; Naville, Danielle; Bégeot, Martine; Saez, J.M.

doi:10.1172/jci117168

Cited by 142 publications

(67 citation statements)

References 22 publications

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“…We believe that these short-term adrenal adaptations may be driven by the initial increase in HPA activity, resulting from the exercise itself or perhaps the running wheel environment. Indeed, ACTH upregulates the expression of its own receptors on adrenocortical cells in such a feed-forward manner (21,28). In accordance with this, 2 wk of voluntary wheel running have recently been shown to increase mRNA levels of StAR (25).…”

Section: Discussionmentioning

confidence: 72%

Voluntary wheel running initially increases adrenal sensitivity to adrenocorticotrophic hormone, which is attenuated with long-term training

Campbell

Rakhshani²,

Fediuc³

et al. 2009

Journal of Applied Physiology

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Campbell JE, Rakhshani N, Fediuc S, Bruni S, Riddell MC. Voluntary wheel running initially increases adrenal sensitivity to adrenocorticotrophic hormone, which is attenuated with long-term training. J Appl Physiol 106: 66 -72, 2009. First published November 13, 2008 doi:10.1152/japplphysiol.91128.2008.-Although exercise is a common and potent activator of the hypothalamic-pituitary adrenal (HPA) axis, the effects of exercise on the acute stress response are not well understood. Here, we investigated the effects of short-(2 wk) and long-term (8 wk) voluntary wheel running on adrenal sensitivity to ACTH stimulation and the acute stress response to restraint in male rats. Diurnal glucocorticoid patterns were measured on days 7 (all groups) and 35 (8-wk groups). Rats were subjected to 20 min of restraint stress on either week 1 or on week 7 of treatment to assess HPA activation. One week later, exogenous ACTH (75 ng/kg) was administered to assess adrenal sensitivity to ACTH. Following this, adrenals were collected and analyzed for key proteins involved in corticosterone (CORT) synthesis. By the end of week 1, exercising (E) animals had twofold higher peak diurnal CORT levels compared with sedentary (S) animals (P Ͻ 0.01). CORT values were not different between groups at week 8. In response to restraint stress at week 2, CORT values in E were approximately threefold greater than in S (P Ͻ 0.05). No difference was found between E and S rats in the response to, or recovery from, restraint at week 8. During the ACTH challenge at week 2, E demonstrated a ϳ2.5-fold increase in adrenal sensitivity compared with S, while no difference was found between E and S at week 8. The expression of steroidogenic acute regulatory protein was found to be ϳ50% higher in the adrenals in E compared with S at week 2 (P Ͻ 0.05), but no difference existed between groups at week 8. These results show that volitional wheel running initially causes hyperactivation of the HPA axis, due to enhanced adrenal sensitivity to ACTH, but that these alterations in HPA activity are completely restored by 8 wk of training. glucocorticoids; corticosterone; adrenocorticotropic hormone; voluntary exercise; circadian rhythm; restraint stress; adrenocorticotropic hormone challenge; glucocorticoid receptor THE HYPOTHALAMIC-pituitary-adrenal (HPA) axis is a vital component of the body's stress response system. This pathway is activated by a variety of stressors that increase the pituitary release of adrenocorticotropic hormone (ACTH) into the circulation. ACTH stimulates the adrenal release of glucocorticoids (GCs), which, in turn, mobilize energy sources for the increased metabolic demands placed on the body. Acutely, this recruitment of energy sources is essential for events, such as physical exercise; however, restoration of the axis is imperative to prevent overexposure to GCs. It has been well established that chronically elevated levels of plasma GCs can lead to the development of a number of harmful pathologies, including impaired insulin signaling, centr...

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Section: Discussionmentioning

confidence: 72%

Voluntary wheel running initially increases adrenal sensitivity to adrenocorticotrophic hormone, which is attenuated with long-term training

Campbell

Rakhshani²,

Fediuc³

et al. 2009

Journal of Applied Physiology

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show abstract

“…We asked whether the adrenal MC2 receptor expression is increased, since this subtype of MC receptor preferentially promotes the ACTH-induced corticosterone response (Chhajlani et al 1993, Liakos et al 1998. In human adrenal fasciculata cells, Ang II and ACTH stimulated the expression of the MC2 receptor (Lebrethon et al 1994, Penhoat et al 1994, Naville et al 2001, Blondet et al 2002. In bovine adrenal fasciculata cells, Ang II was hypothesized to induce a steroidogenic desensitization (Penhoat et al 1995), justifying our speculation that the MC2 receptor is increased in TGR(ASrAOGEN).…”

Section: Discussionmentioning

confidence: 99%

Stress sensitivity is increased in transgenic rats with low brain angiotensinogen

Müller

Kröger²,

Szymczak³

et al. 2009

Journal of Endocrinology

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AT 1 blockers attenuate hypothalamo-pituitary-adrenal (HPA) axis reactivity in hypertension independently of their potency to lower blood pressure. A reduced pituitary sensitivity to CRH and a downregulation of hypothalamic CRH expression have been suggested to influence HPA axis activity during chronic AT 1 blockade. This study was aimed at confirming the role of central angiotensin II in regulating HPA reactivity by using the transgenic rat TGR(ASrAO-GEN), a model featuring low levels of brain angiotensinogen. Different stress tests were performed to determine HPA reactivity in TGR(ASrAOGEN) and appropriate controls. In TGR(ASrAOGEN), blood pressure was diminished compared to controls. The corticosterone response to a CRH or ACTH challenge and a forced swim test was more distinct in TGR(ASrAOGEN) than it was in controls and occurred independently of a concurrent enhancement in ACTH. Using quantitative real-time PCR, we found increased mRNA levels of melanocortin 2 (Mc2r) and AT 2 receptors (Agtr2) in the adrenals of TGR(ASrAOGEN), whereas mRNA levels of Crh, Pomc, and AT 1 receptors (Agtr1) remained unchanged in hypothalami and pituitary glands. Since stress responses were increased rather than attenuated in TGR(ASrAOGEN), we conclude that the reduced HPA reactivity during AT 1 blockade could not be mimicked in a specific transgenic rat model featuring a centrally inactivated renin-angiotensin-aldosterone system. The ACTH independency of the enhanced corticosterone release during CRH test and the enhanced corticosterone response to ACTH rather indicates an adrenal mechanism. The upregulation of adrenal MC2 and AT 2 receptors seems to be involved in the stimulated facilitation of adrenal corticosterone release for effectuating the stimulated stress responses.

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“…This effect is associated with increased production of cortisol. Studies of human, bovine and ovine adrenocortical cells in culture suggest that ACTH upregulates ACTH-R mRNA expression at both transcriptional and posttranscriptional level (Lebrethon et al 1994b, Penhoat et al 1994, Picard-Hagen et al 1997. There is also evidence for glucocorticoid regulation of ACTH-R protein and mRNA.…”

Section: Discussionmentioning

confidence: 99%

Developmental regulation of corticotrophin receptor gene expression in the adrenal gland of the ovine fetus and newborn lamb: effects of hypoxia during late pregnancy

Fraser

Braems²,

Challis³

2001

Journal of Endocrinology

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Responsiveness of the fetal sheep adrenal gland to adrenocorticotrophin (ACTH) increases in late pregnancy, resulting in increased glucocorticoid production. Development of this responsiveness is an important determinant of fetal hypothalamic-pituitary-adrenal function and depends, in part, on the potential for ACTH binding to adrenal tissue. In the present study, we have examined the developmental pattern of ACTH receptor (ACTH-R) expression during the latter half of pregnancy and in neonatal and adult life. As hypoxaemia induces increases in cortisol and ACTH secretion, in addition to increasing fetal adrenal responsiveness, a further aim of this study was to investigate whether hypoxaemia was associated with altered expression of the ACTH-R gene.Whole adrenal glands were removed from fetal sheep, lambs and adult sheep at different stages of development for measurement of ACTH-R mRNA. Moderate hypoxaemia was induced for 48 h beginning on days 124-128, or on days 132-134 of gestation, by decreasing the maternal fractional inspired oxygen. ACTH-R mRNA was detected by northern blotting using a cDNA cloned in our laboratory and by in situ bydridisation.ACTH-R mRNA (3·6 kb major transcript) was detected in adrenal tissue at day 63 of gestation. Its relative abundance increased significantly (P<0·05) between days 126-128 and 140-141 of pregnancy, increased further with the onset of spontaneous labour, and remained increased in newborn lambs at 7 h-7 days after birth. ACTH-R mRNA levels then decreased in adrenal tissue from lambs and adult sheep (P<0·05). Hypoxaemia for 48 h significantly increased ACTH-R mRNA expression in adrenals of the older fetuses (days 134-136) compared with that in controls (P<0·05), but was without effect in younger fetuses.We conclude that levels of ACTH-R mRNA in the fetal adrenal gland increase as term approaches, coincident with the endogenous prepartum surge in plasma ACTH and cortisol. Sustained hypoxaemia resulted in an upregulation of mRNA encoding for ACTH-R, but only in older fetuses and in association with a sustained increase in plasma cortisol. These results are consistent with cortisol, ACTH, or both, contributing to increased fetal adrenal responsiveness, by increasing expression of fetal adrenal receptors for ACTH.

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Regulation of corticotropin receptor number and messenger RNA in cultured human adrenocortical cells by corticotropin and angiotensin II.

Cited by 142 publications

References 22 publications

Voluntary wheel running initially increases adrenal sensitivity to adrenocorticotrophic hormone, which is attenuated with long-term training

Voluntary wheel running initially increases adrenal sensitivity to adrenocorticotrophic hormone, which is attenuated with long-term training

Stress sensitivity is increased in transgenic rats with low brain angiotensinogen

Developmental regulation of corticotrophin receptor gene expression in the adrenal gland of the ovine fetus and newborn lamb: effects of hypoxia during late pregnancy

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