L'istofisiologia della corteccia surrenale

A considerable number of problems related to the histophysiology of the adrenal cortex is updated and discussed in full detail

Ovariectomy-induced changes in the adrenal cortex of spontaneously hypertensive rats

Many lines of evidence indicate that adrenocortical steroid hormones are involved in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). Twenty-eight days after ovariectomy a notable decrease in the sistolic blood pressure (BP) was found in SHR, along with a marked atrophy of their adrenal cortices. The hypothesis is advanced that the ovariectomy-induced lowering in BP in SHR may be, at least partly, mediated by the suppression of the adrenal secretory activity, due to the lack of circulating estrogens, which are well known to stimulate hypophyseal ACTH release

Different effects of neurotensin and neuromedin-N on the proliferative activity of rat adrenal cortex

Evidence indicates that neurotensin (NT) and neuromedin-N (NMN) exerts an adrenocorticotropic effect in the rat. The present study aimed to investigate whether these neuropeptides are able to stimulate the proliferation of rat adrenocortical cells in vivo and to compare their mode of action. Adrenocortical proliferative activity was assessed by the metaphasearrest technique and metaphases were counted per medulla-containing adrenal section. A bolus administration of NT (3 pglrat) resulted in a significant increase in the number of metaphases in both zona fasciculata and the entire cortex, an effect observed 48 h after the in.jection. The administration of NMN (3 yglrat) induced a notable rise in the number of metaphases in the zona fasciculata and the entire cortex within 12 h, followed by a subsequent drop after 24 h and a return to normal values at 48 h. These findings indicate that NT and NMN enhance rat adrenal growth in vivo acting via different mediators

Proliferation and distribution of adrenocortical cells in the gland of ACTH- or dexamethasone-treated rats

The effects of prolonged (7-day) ACTH and dexamethasone administrations on rat adrenocorticalcell turnover have been investigated by combined stereological and metaphase-arrest techniques. ACTH was found to increase the number of parenchymal cells in each adrenal zone; however, ACTH altered the cell distribution in the cortex, lowering their percentage in the zona glomerulosa (ZG) and zona fasciculata (ZF) and enhancing it in the zona reticularis (ZR). The cell birth-rate was markedly raised by ACTH exclusively in ZG and ZF. Dexamethasone notably decreased the number of ZF and ZR cells, without altering that of ZG cells. Moreover. dexamethasone increased the percentage of parenchymal cells in ZG and ZF, and lowered it in ZR. In the adrenal cortices of dexamethasoneadministered animals, metaphases were virtually absent. These data indicate that ACTH increases the cell birthrate in ZG and possibly ZF, and enhances the centripetal migration of newly-formed cells and their accumulation in ZR. Dexamethasone inhibits both proliferation of adrenocortical cells in the outer cortical layers and their centripetal migration into ZR. Moreover, it appears to cause parenchymal-cell loss in the inner adrenocortical layers

Nonclassic endogenous regulators of angiogenesis

Angiogenesis, the process through which new blood vessels arise from preexisting ones, is regulated by several "classic" factors, among which the most studied are vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). In recent years, investigations showed that, in addition to the classic factors, numerous endogenous peptides play a relevant regulatory role in angiogenesis. Such regulatory peptides, each of which exerts well-known specific biological activities, are present, along with their receptors, in the blood vessels and may take part in the control of the "angiogenic switch." An in vivo and in vitro proangiogenic effect has been demonstrated for erythropoietin, angiotensin II (ANG-II), endothelins (ETs), adrenomedullin (AM), proadrenomedullin N-terminal 20 peptide (PAMP), urotensin-II, leptin, adiponectin, resistin, neuropeptide-Y, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), and substance P. There is evidence that the angiogenic action of some of these peptides is at least partly mediated by their stimulating effect on VEGF (ANG-II, ETs, PAMP, resistin, VIP and PACAP) and/or FGF-2 systems (PAMP and leptin). AM raises the expression of VEGF in endothelial cells, but VEGF blockade does not affect the proangiogenic action of AM. Other endogenous peptides have been reported to exert an in vivo and in vitro antiangiogenic action. These include somatostatin and natriuretic peptides, which suppress the VEGF system, and ghrelin, that antagonizes FGF-2 effects. Investigations on "nonclassic" regulators of angiogenesis could open new perspectives in the therapy of diseases coupled to dysregulation of angiogenesis

Effects of bombesin and neuromedin-B on the proliferative activity of the rat adrenal cortex

Bombesin (BM) and neuromedin-B (NMB) exert similar biological effects, acting via two functionally distinct BM-receptor subtypes. The present study aimed to investigate whether BM and NMB stimulate the proliferation of rat adrenocortical cells and to compare their mode of action. Adult female rats were treated with a single subcutaneous dose of 3 pg BM or NMB. Adrenocortical proliferative activity was assessed by the metaphase-arrest technique. BM administration resulted in a marked increase in the number of metaphases in zona glomerulosa (ZG) and zona fasciculata (ZF), and in the entire cortex. This increase appeared 24 h after injection in the ZG, and after 48 h in the ZF. NMB adrninistration, on the other hand, caused a prompt increase in the number of metaphases in the ZG and entire cortex at 12 h, followed by a subsequent drop below the control leve1 at 24 and 48 h of experiment. These findings indicate that BM and NMB enhance the proliferative activity of rat adrenocortical cells acting via different receptors or different mediators

Prolonged kallikrein inhibition does not affect the basal growth and secretory capacity of rat adrenal cortex, but enhances mineralo- and glucocorticoid response to ACTH and handling stress

The effects on the pituitary-adrenocortical functions of the prolonged (7-day) blockade of endogenous bradykinin (BK) synthesis, obtained by the administration of the kallikrein inhibitor (K-I) cyclohexylacetyl-Phe-Arg-Ser-Val-Gln amide, were investigated in the rat. K-I treatment did not cause significant changes in the (i) body and adrenal weights; (ii) basal plasma levels of ACTH, aldosterone and corticosterone; and (iii) average volume of adrenocortical cells and their basal secretory capacity. Conversely, K-I administration induced a significant magnification of the in vivo mineralo- and glucocorticoid responses to the intraperitoneal (i.p.) bolus injection of ACTH. Moreover, K-I-treated rats, but not control ones, displayed a moderate and short-term adrenal secretory response to the mild stress evoked by the placebo i.p. injection. Collectively, these findings rule out the possibility that endogenous BK plays a relevant role in the control of adrenocortical function under basal conditions. However, they suggest that endogenous BK may be involved in quenching exceedingly high adrenocortical responses to ACTH and stresses

Effects of pneumadin (PNM) on the adrenal glands. 5.Potent stimulating action of PNM on adrenocortical growth of dexamethasone-administered rats

Pneumadin (PNM) is a biologically active decapeptide, originally isolated from mammalian lungs, that has been previously found to acutely stimulate pituitary-adrenocortical axis in rats. The effects of 2-day PNM administration on the atrophic adrenal cortices of rats treated for 8 days with dexamethasone (DX) were investigated. PNM significantly raised adrenal weight and the average volume of adrenocortical cells. The decapeptide strikingly increased ACTH plasma concentration; however, the blood levels of aldosterone and corticosterone, as well as steroid output by adrenal quarters were not apparently affected. In light of these findings the following conclusions can be drawn: (i) PNM enhances the growth of adrenal cortex in DXadministered rats by a mechanism involving the stimulation of ACTH release; and (ii) PNM treatment is probably too short to allow DX-atrophied adrenocortical cells to re-acquire al1 their differentiated secretory capacities

Endothelin-1 [1-311 acts as a selective ETA-receptor agonist in the rat adrenal cortex

Endothelin-1 (ET-1) is a 21-amino acid residue (ET-1[1-211) hypertensive peptide, which together with its receptor subtypes A and B (ETA and ETB) is expressed in the rat adrenal cortex, where it stimulates steroid-hormone (aldosterone and corticosterone) secretion through the ETB receptor and the growth (proliferative activity) of the zona glomerulosa (ZG) through the ETA receptor. ET-1[1-211 is generated from bigET-1 by the endothelin-converting enzyme (ECE-1). However, recent evidence indicates the existence of an alternative chymase-mediated biosynthetic pathway leading to the production of an ET- 1[1-311 peptide, which was found to reproduce the ETA receptor-mediated vascular effects of ET-l[l-211. We found that ET-1[1-211, but not ET-1[1-311, concentration-dependently raised steroid secretion from dispersed rat adrenocortical cells, its effect being blocked by the ETB-receptor selective antagonist BQ- 788. Both ET-1s concentration-dependently increased the number of "S-phase" cells (as detected by the 5- bromo-2'-deoxyuridine immunocytochemical method) in capsule-ZG strips within a 240 min incubation. The ZG proliferogenic action of both ET-1s was blocked by the ETA-receptor antagonist BQ-123, and ET-l[l-311 was found to be significantly more potent than ET-1[1- 211. Autoradiography showed that in the rat adrenal ET- 1[1-211 displaced the binding of selective ligands to both ETA ( [ 1 2 5 ~ ] ~ ~1-21425) and ETB receptors ( [ 1 2 5 ~ ] ~ ~ - 3020), while ET-l[l-311 eliminates only the binding to ETA receptors. Collectively, our findings provide strong evidence that ET-1[1-311 acts in the rat adrenal glands as a selective ETA-receptor agonist, mainly involved in the stimulation of ZG proliferative activity

Effects of the prolonged administration of bradykinin on the rat pituitary-adrenocortical axis

The effects of a prolonged administration of bradykinin (BK) andlor D-Arg, [Hyp3, D - P ~ ~ ~ I - aB K , specific antagonist of BK receptors (BK-A) (daily subcutaneous injections of 4 nmol/rat for 6 days) on the function of the pituitary-adrenocortical axis were investigated. BK did not change plasma aldosterone concentration (PAC), but markedly lowered that of corticosterone (PBC) and consequently induced a compensatory hypersecretion of ACTH by the pituitary gland. BK-A did not apparently affect the function and growth of the adrenal gland, but, when administered together with BK, markedly raised both PAC and PBC, and provoked a significant atrophy of the adrenal gland, probably due to loss of parenchymal cells. Taken together, these rather puzzling findings do not appear to provide clear evidence for the involvement of BK in the physiological regulation of adrenocortical growth and steroidogenic capacity in rats