Differential expression of VEGF receptors in adrenal atrophy induced by dexamethasone: a protective role of ACTH

Mallet, Christine; Féraud, Olivier; Ouengue-Mbélé, Gaehl; Gaillard, Isabelle; Sappay, Nicolas; Vittet, Daniel; Vilgrain, Isabelle

doi:10.1152/ajpendo.00450.2001

Cited by 24 publications

(17 citation statements)

References 55 publications

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“…Glucocorticoid treatment has been shown to decrease VEGF protein expression in several tumor cells (Koedam et al 2002;Iwai et al 2004) and in the adrenal gland (Mallet et al 2003), but little was known about the eVect that glucocorticoid treatment would have on skeletal muscle. Our results revealed an important reduction of VEGF protein expression, which was not prevented by exercise training.…”

Section: Discussionmentioning

confidence: 99%

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Exercise training prevents hyperinsulinemia, muscular glycogen loss and muscle atrophy induced by dexamethasone treatment

et al. 2009

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This study investigated whether exercise training could prevent the negative side effects of dexamethasone. Rats underwent a training period and were either submitted to a running protocol (60% physical capacity, 5 days/week for 8 weeks) or kept sedentary. After this training period, the animals underwent dexamethasone treatment (1 mg/kg per day, i.p., 10 days). Glycemia, insulinemia, muscular weight and muscular glycogen were measured from blood and skeletal muscle. Vascular endothelial growth factor (VEGF) protein was analyzed in skeletal muscles. Dexamethasone treatment evoked body weight loss (-24%), followed by muscular atrophy in the tibialis anterior (-25%) and the extensor digitorum longus (EDL, -15%). Dexamethasone also increased serum insulin levels by 5.7-fold and glucose levels by 2.5-fold compared to control. The exercise protocol prevented atrophy of the EDL and insulin resistance. Also, dexamethasone-treated rats showed decreased muscular glycogen (-41%), which was further attenuated by the exercise protocol. The VEGF protein expression decreased in the skeletal muscles of dexamethasone-treated rats and was unaltered by the exercise protocol. These data suggest that exercise attenuates hyperglycemia and may also prevent insulin resistance, muscular glycogen loss and muscular atrophy, thus suggesting that exercise may have some benefits during glucocorticoid treatment.

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Section: Discussionmentioning

confidence: 99%

“…Decreases in VEGF expression induced by glucocorticoid treatment has been shown in several tumor cells (Koedam et al 2002;Iwai et al 2004) and in the adrenal gland (Mallet et al 2003), but little is known about its eVect on skeletal muscle.…”

Section: Introductionmentioning

confidence: 99%

Exercise training prevents hyperinsulinemia, muscular glycogen loss and muscle atrophy induced by dexamethasone treatment

et al. 2009

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“…This observation supports previous work supporting a role for ACTH in the maintenance of adrenal cortical mass under nonstress conditions. For example, circadian increases in fasciculata cell proliferation that are preceded by increases in plasma ACTH can be blocked by dexamethasone (34), and adrenal atrophy produced by chronic dexamethasone treatment can be prevented (28,40) or reversed (29) by ACTH replacement. In contrast to its suppressive effect in the outer fasciculata, dexamethasone treatment unmasked a proliferative response to unilateral adrenalectomy in glomerulosa cells.…”

Section: Discussionmentioning

confidence: 99%

Zone-specific cell proliferation during compensatory adrenal growth in rats

Engeland¹,

Ennen²,

Elayaperumal³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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Compensatory adrenal growth after unilateral adrenalectomy (ULA) leads to adrenocortical hyperplasia. Because zonal growth contributions are not clear, we characterized the phenotype of cortical cells that proliferate using immunofluorescence histochemistry and zone-specific cell counting. Rats underwent ULA, sham adrenalectomy (sham), or no surgery and were killed at 2 or 5 days. Adrenals were weighed and sections immunostained for Ki67 (proliferation), cytochrome P-450 aldosterone synthase (P450aldo, glomerulosa), and cytochrome P-450 11␤-hydroxylase (P45011␤, fasciculata). Unbiased stereology was used to count proliferating glomerulosa and fasciculata cells. Adrenal weight increased after ULA compared with sham and no surgery at both time points, and there was no difference between sham and no surgery. However, either ULA or sham increased Ki67-positive cells in the outer fasciculata at both time points compared with no surgery. Outer fasciculata-restricted proliferation is thus associated with adrenal weight gain in ULA but not sham. Experiment repetition using proliferating cell nuclear antigen and bromodeoxyuridine showed similar results. After ULA, adrenal DNA, RNA, and protein increased at both time points, whereas after sham, only adrenal DNA increased at 2 days. Compensatory growth thus results from hyperplasia and hypertrophy, whereas sham induces only a transient adrenal hyperplasia. Dexamethasone pretreatment prevented the increase in adrenal weight after ULA and blocked Ki67 labeling in the outer fasciculata but not zona glomerulosa in all groups. These results clearly show that the outer fasciculata is the primary adrenal zone responsible for compensatory growth, responding to steroid-suppressible stress signals that alone are ineffective in increasing adrenal mass. adrenal cortex; stress; zona fasciculata; zona glomerulosa; adrenal weight COMPENSATORY ADRENAL GROWTH after unilateral adrenalectomy is a well established model of adrenal growth in rodents. The increase in adrenal weight results from cell proliferation, as reflected by increases in adrenal DNA content (11,36). Although increases in weight are restricted to the adrenal cortex and not the medulla (10, 43), it is unclear which cortical zones are responsible for the growth response. Using [ 3 H]thymidine incorporation as an index of proliferation, Reiter and Pizzarello (38) reported increased in vivo labeling in the capsule, glomerulosa, and outer fasciculata after unilateral adrenalectomy in rats, with the largest response in the fasciculata. The finding of proliferation in the capsule and zona glomerulosa in rats after unilateral adrenalectomy is consistent with studies showing increased incorporation of [ 3 H]thymidine in vitro in adrenal capsule-glomerulosa tissue (2). After unilateral adrenalectomy in mice, labeling for proliferating cell nuclear antigen (PCNA) was increased in cells adjacent to the capsule, suggesting that glomerulosa cells were responsible for the growth response in this species (4). However, other studies have su...

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“…VEGF receptors on adrenal cells in tissue and in culture clearly identified by us and others would thus allow for binding of circulating and also of locally produced VEGF. 30,31 Local VEGF concentrations are high in pregnancy, thus effects of autocrine or systemic VEGF might account for the adrenal epithelial cell responses. The VEGF homolog placenta growth factor-1, also highly expressed in pregnancy, is capable of binding to Flt-1, yet not to Kdr.…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factor-A and Aldosterone

et al. 2013

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Abstract-Aldosterone levels are markedly elevated during normal pregnancy but fall even though volume contracts when preeclampsia occurs. The level of aldosterone in either condition cannot be explained solely by the activity of the renin-angiotensin II system. In normal gestation, vascular endothelial growth factor (VEGF) is thought to maintain vascular health, but its role in adrenal hormone production is unknown. We hypothesized that the role of VEGF in the adrenal gland is to maintain vascular health and regulate aldosterone production. Here, we demonstrate that supernatant of endothelial cells grown in the presence of VEGF enhanced aldosterone synthase activity in human adrenocortical cells. VEGF either alone or combined with angiotensin II increased aldosterone production in adrenal cells. These data suggest that endothelial cell-dependent and independent activation of aldosterone is regulated by VEGF. In contrast to angiotensin II, VEGF did not upregulate the steroidogenic acute regulatory protein. Consistent with this observation, angiotensin II stimulated both aldosterone and cortisol synthesis from progesterone, whereas VEGF stimulated selectively aldosterone production. In rats, overexpression of soluble fms-like tyrosine kinase-1, an endogenous VEGF inhibitor, led to adrenocortical capillary rarefaction and fall in aldosterone concentrations that correlated inversely with soluble fms-like tyrosine kinase-1 levels. These findings may explain why aldosterone increases so markedly during normal gestation and why preeclampsia, a condition characterized by high soluble fms-like tyrosine kinase-1, is associated with inappropriately low aldosterone levels in spite of relatively lower plasma volumes. (Hypertension. 2013;61:1111-1117.) • Online Data SupplementKey Words: adrenal cell ■ aldosterone ■ aldosterone synthase ■ preeclampsia ■ soluble fms-like tyrosine kinase-1 ■ steroidogenic acute regulatory protein ■ vascular endothelial growth factor

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Differential expression of VEGF receptors in adrenal atrophy induced by dexamethasone: a protective role of ACTH

Cited by 24 publications

References 55 publications

Exercise training prevents hyperinsulinemia, muscular glycogen loss and muscle atrophy induced by dexamethasone treatment

Exercise training prevents hyperinsulinemia, muscular glycogen loss and muscle atrophy induced by dexamethasone treatment

Zone-specific cell proliferation during compensatory adrenal growth in rats

Vascular Endothelial Growth Factor-A and Aldosterone

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