ACTH-regulated expression of vascular endothelial growth factor in the adult bovine adrenal cortex: A possible role in the maintenance of the microvasculature

Abstract

Endothelial cells lining vessels of endocrine tissues are fenestrated. Interactions with the local environment via either soluble factors or cell-cell interactions appear to govern this terminal endothelial differentiation. Adrenocorticotropin (ACTH) has previously been reported to modulate endothelial fenestration in the rat adrenal cortex. Since vascular endothelial growth factor (VEGF) has been characterized as a potent inducer of endothelial fenestration, we aimed to characterize the status of VEGF expression in the bovine adult adrenal cortex and asked whether ACTH may regulate VEGF expression. By immunohistochemical analysis, we observed VEGF expression in steroidogenic cells from both zona glomerulosa and zona fasciculata of the bovine adrenal cortex. Double-labeling experiments performed on isolated cells in primary culture revealed VEGF immunoreactivity, essentially colocalized with the Golgi apparatus. The expression of two predominant VEGF isoforms, VEGF(121) and VEGF(165), was observed by RT-PCR analysis. ACTH (10 nM) was found to rapidly (within 2-4 h) increase the abundance of these VEGF transcripts, as assessed by both RT-PCR and Northern blot analysis. In parallel, ACTH significantly induced VEGF secretion into the medium of fasciculata cells in primary culture. Thus, our data are consistent with the involvement of ACTH, through its regulation of VEGF expression, in the maintenance of the adult adrenal cortex endothelium.

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

“…In the adult, regulation of VEGF and its receptors has been observed in some endocrine tissues, such as ovary, thyroid, and prostate, in various conditions pointing to a hormonal control of the vasculature (3,25,28,45,49). Immunohistochemical experiments have reported that the steroidogenic cells in adult bovine adrenal gland express VEGF (17). In addition, VEGF mRNA can be detected in human fetal (44) and in adult bovine (17) adrenocortical cells in in vitro culture.…”

“…The effect was transient within 2 h of agonist stimulation (17). Similar results were also described in primary cultures of human fetal adrenocortical cells stimulated with ACTH or forskolin (28).…”

“…Fresh adrenal glands were embedded in OCT compound (Miles Scientific, Elkhart, IN) after fixation in 4% paraformaldehyde for 1 h at 4°C and cryoprotection in 20% (wt/vol) sucrose. Frozen sections (10 m thick) were mounted onto gelatin-coated glass slides, air-dried overnight, and processed for indirect immunofluorescence microscopy as previously described (17).…”

“…Immunohistochemical experiments have reported that the steroidogenic cells in adult bovine adrenal gland express VEGF (17). In addition, VEGF mRNA can be detected in human fetal (44) and in adult bovine (17) adrenocortical cells in in vitro culture. Furthermore, the expression of VEGF receptors (VEGFRs)-1 and -2 at the mRNA level has also been detected in adrenocortical capillary endothelial cell in culture (51) but not in steroidogenic cells (data not shown).…”

High plasma VEGF relates to low carbohydrate intake in patients with type 2 diabetes

“…Previous findings indicate that the hypothalamus, pituitary and adrenal gland participate in VEGF production and secretion. 28,29 Circulating VEGF binds to high affine receptors that are widely distributed throughout the vasculature system. 10 The highest density of VEGF binding sites has been demonstrated in the vessels of the brain.…”