Dual Hormonal Regulation of Endocrine Tissue Mass and Vasculature by Adrenocorticotropin in the Adrenal Cortex

Abstract

The mass of healthy adult tissues is stable and their vasculature is quiescent, but this equilibrium is disrupted under certain physiological or pathological situations. There is an emerging concept indicating that these trophic changes may be initiated by modifications of the vasculature. In the current study, we documented over a period of 14 d the serial alterations occurring in both endocrine and endothelial compartments during adrenal atrophy induced by ACTH suppression in mice. After dexamethasone perfusion, a rapid fall of plasmatic ACTH and corticosterone concentrations was observed within the first 24 h. During the first 4 d of treatment, adrenal weight and adrenal cortex cellularity decreased rapidly. This was correlated with an inhibition of cell proliferation and a massive induction of endocrine cell apoptosis. Between d 4 and d 14, a slower but sustained decay of adrenal cortex size and cellularity was observed. This second phase was associated with progressive loss of vascular endothelial growth factor protein expression in the endocrine cells and regression of the vascular network. These data support the concept that ACTH controls adrenal cortex trophicity through a dual mechanism involving its antiapoptotic effect on endocrine cells and its indirect vascular endothelial growth factor-mediated action on endothelial cells.

Mitogenic functions of endocrine gland-derived vascular endothelial growth factor and Bombina variegata 8 on steroidogenic adrenocortical cells

“…Interestingly, the level of expression of angiogenic factors, such as vascular endothelial growth factor-A (VEGF-A), is high in these organs despite the absence of active angiogenesis, suggesting that these factors play an important role in the homeostasis and the hormonal control of the microvasculature (Shweiki et al 1993). Our team has previously established that VEGF expression is under the hormonal control of adrenocorticotropin (ACTH) both in primary cultures of bovine steroidogenic adrenocortical cells in vitro and in mouse adrenal gland in vivo (Gaillard et al 2000, Thomas et al 2004, Cherradi et al 2006. However, besides VEGF, a number of other angiogenic factors have been described, which may also be expressed in the adrenal cortex and participate in the regulation of its vascularization.…”

A novel concept in antiangiogenic and antitumoral therapy: multitarget destabilization of short-lived mRNAs by the zinc finger protein ZFP36L1

“…While the capillaries in the zona fasciculata-reticularis paralleled the columns of steroidogenic cells in control animals, the vascular network in R9-ZFP36L1-treated animals appeared discontinuous. These histological modifications were reminiscent of those obtained during dexamethasone-induced adrenal cortex regression, a condition when VEGF protein levels are also dramatically reduced (Thomas et al, 2004). In order to check whether R9-ZFP36L1-mediated decrease in VEGF protein expression in the adrenal cortex was correlated with VEGF mRNA levels, the expression of the different VEGF mRNA isoforms was analyzed by RT-PCR (Figure 6b).…”

“…In the adrenal cortex, the rapid release of corticosteroids into the blood flow is facilitated by a dense vascular network whose maintenance is regulated through strong VEGF expression at the adult stage (Thomas et al, 2004). A single injection of R9-ZFP36L1 in the adrenal gland induced a massive decrease in VEGF protein levels throughout the adrenal cortex after 24 h, indicating an efficient internalization of R9-ZFP36L1 and probably a bystander effect.…”

Blockade of nitric oxide synthesis stimulates the activity of adrenal cortex

“…Primarno mesto delovanja ovog hormona su steroidogene ćelije zone facikulate (ZF), koje brzo reaguju na stimulaciju, i zone retikularis (ZR), koje održavaju, kako bazalnu tako i sekreciju glukokortikoida izazvanu prolongiranom stimulacijom sa ACTH (5). U nedostatku ACTH inhibirana je steroidogeneza i nastaje atrofija korteksa (6).…”