Biomedical subjects

P Rebuffat

Publications and source records attributed to P Rebuffat.

At least 37 records · Page 2Linked to original sources

PubMed1998

Vasoactive intestinal peptide stimulates rat adrenal glucocorticoid secretion, through an ACTH receptor-dependent activation of the adenylate cyclase signaling pathway.

Vasoactive intestinal peptide (VIP) concentration-dependently enhanced corticosterone and cyclic-AMP release by dispersed rat inner adrenocortical cells. A VIP-receptor antagonist and the ACTH-receptor antagonist corticotropin-inhibiting peptide annulled both adrenocortical-cell responses to VIP, while the protein kinase (PKA) inhibitor H-89 blocked only corticosterone response. Collectively, these findings suggest that VIP stimulates glucocorticoid secretion of rat adrenals, through the aspecific activation of ACTH receptors coupled with the adenylate cyclase/PKA-dependent signaling pathway.

Adenylyl Cyclases↗

PubMed1997

Effects of adrenomedullin and proadrenomedullin N-terminal 20 peptide on rat zona glomerulosa cells.

Adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) derive from a 185-amino acid prohormone, called preproadrenomedullin, which is highly expressed in rat adrenal medulla. ADM and PAMP did not affect either basal or ACTH-stimulated aldosterone secretion of dispersed rat zona glomerulosa cells In contrast, both peptides markedly suppressed angiotensin-II-stimulated aldosterone production, PAMP being much more effective than ADM (minimal effective concentration, 10(-10) M versus 10(-8) M. IC50, 2.0 +/- 0.17 x 10(-9) M versus 3.1 +/- 0.22 x 10(-8) M; P<0.01. Maximum inhibition, 80% versus 43%, respectively). The inhibitory effect of 10(-7) M ADM was completely reversed by the competitive antagonist of type 1 calcitonin gene-related peptide (CGRP) receptors CGRP(8-37) (10(-6) M), while that of 10(-7) M PAMP did not, thereby suggesting that this last peptide acts through specific receptors. Collectively, these findings may suggest that of the two main preproadrenomedullin derived peptides is PAMP which has probably to be considered a physiologic inhibitor of mineralocorticoid secretion in rats.

Adrenocorticotropic Hormone↗

PubMed1997

Neurotensin stimulates CRH and ACTH release by rat adrenal medulla in vitro.

Neurotensin (NT) is a 13-amino acid peptide, widely distributed in the central and peripheral nervous system, which is able to stimulate the activity of the hypothalamo-pituitary CRH-ACTH system. We investigated by RIA the effect of NT on the release of CRH and ACTH immunoreactivities (ir) by rat adrenal medulla in vitro. NT enhanced the release of both CRH-ir and ACTH-ir, the maximal effective concentration being 10(-8) M. [D-Trp11]-NT, a specific NT receptor antagonist, abrogated the effects of NT. The stimulatory effect of 10(-8) M NT on ACTH-ir release was blocked by alpha-helical-CRH (an antagonist of CRH receptors), thereby suggesting that the enhancement in ACTH secretion is consequent to the stimulation of CRH release. These findings suggest that NT is a stimulator not only of the central (hypothalamo-pituitary), but also of the peripheral (intramedullary), branch of the CRH-ACTH system.

Adrenal Medulla↗

PubMed1997

Arginine-vasopressin stimulates CRH and ACTH release by rat adrenal medulla, acting via the V1 receptor subtype and a protein kinase C-dependent pathway.

Arginine-vasopressin (AVP) is a hypothalamic hormone that, like CRH, stimulates the pituitary release of ACTH, thereby activating adrenal glucocorticoid secretion. Evidence indicates that rat adrenal medulla contains a CRH-ACTH system duplicating that existing at the hypothalamo-pituitary level and involved in the paracrine stimulation of the cortex secretion. Therefore, we investigated by RIA the effect of AVP on the release of CRH and ACTH immunoreactivities (IR) by rat adrenal medulla in vitro. AVP concentration-dependently enhanced the release of both CRH-IR and ACTH-IR, and the effect was blocked by a selective antagonist of the V1 subtype of AVP receptors. The CRH receptor antagonist alpha-helical-CRH partially reversed AVP-evoked rise in ACTH-IR release, without altering either CRH response or basal secretions of CRH and ACTH. The specific inhibitors of protein kinase C Ro31-8220 and calphostin C abolished both CRH and ACTH responses to AVP. In conclusion, our present findings suggest that AVP stimulates intramedullary the CRH-ACTH system, acting via V1 receptors and activating protein kinase C.

Adrenal Medulla↗

PubMed1997

Different mechanisms mediate the in vivo aldosterone and corticosterone responses to 5-bromo-2'-deoxyuridine in rats.

The subcutaneous injection of 5'-bromo-2' deoxyuridine (BrdU) was found to raise the plasma concentrations of ACTH, aldosterone and corticosterone in rats. The aldosterone response was observed at a lower dose of BrdU and lasted for a longer period than those of ACTH and corticosterone (1.25 versus 2.50 mg/100 g body weight; 48 versus 24 h). Corticosterone response to BrdU was partially reversed by the ACTH-receptor antagonist corticotropin-inhibiting peptide (CIP), and aldosterone response by the arginine vasopressin (AVP) V1-receptor antagonist [amino-Pen1, Val4,D-Arg8]-vasopressin (AVP-A). The angiotensin-II (ANG-II)-receptor antagonist [Sar1, Val5, Ala8]-ANG-II (SAR) was ineffective. CIP, AVP-A and SAR, when administered alone, did not alter basal levels of ACTH, aldosterone and corticosterone. In light of these findings the following conclusions can be drawn: (i) BrdU stimulates the hypothalamo-pituitary-adrenal axis in rats, and this effect may influence the results of cell-kinetics studies carried out with the BrdU-labelling technique, especially in those tissue that are highly responsive to glucocorticoids (e.g. pituitary, adrenal and lymphatic tissues); and (ii) different mechanisms underlie the aldosterone and corticosterone secretagogue effects of BrdU, the former being at least in part dependent on the stimulation of AVP release and the latter on the rise in ACTH secretion.

Aldosterone↗

PubMed1997

Endothelins stimulate deoxyribonucleic acid synthesis and cell proliferation in rat adrenal zona glomerulosa, acting through an endothelin A receptor coupled with protein kinase C- and tyrosine kinase-dependent signaling pathways.

The effects of endothelins (ET) on the proliferative activity of the rat adrenal cortex have been investigated in vivo, using an in situ perfusion technique of the intact left gland. The chemicals were dissolved in the perfusion medium, and the perfusion continued for 120 min. ET-1 concentration dependently increased the mitotic index and [3H]thymidine incorporation into DNA in the zona glomerulosa (ZG; 6- and 3-fold increases, respectively, at a 10(-8) M concentration), but not in the inner adrenocortical layers, where the basal proliferative activity was negligible. The effect of 10(-8) M ET-1 was blocked by the ETA receptor antagonist BQ-123, whereas the ETB receptor antagonist BQ-788 was ineffective. ET-2 and ET-3 (10(-8) M) enhanced DNA synthesis in the ZG, but their effects were less intense than that of 10(-8) M ET-1 and were directly related to their binding potency for the ETA receptor subtype (ET-1 > ET-2 >> ET-3). The selective ETB receptor agonists BQ-3020, IRL-1620, and sarafotoxin-6B were ineffective. The ZG proliferogenic action of 10(-8) M ET-1 was reversed by both the protein kinase C inhibitor Ro31-8220 and the tyrosine kinase inhibitor tyrphostin-23; a complete blockade was obtained at a 10(-6)-M concentration of each inhibitor. In contrast, neither the protein kinase A inhibitor H-89 (10(-5) M) nor the cyclooxygenase and lipoxygenase inhibitors indomethacin and phenidone (10(-5) M) affected ET-1 action. Collectively, our findings indicate that ETs stimulate the proliferation of rat adrenal ZG cells, acting through ETA receptors coupled with protein kinase C- and tyrosine kinase-dependent signaling pathways. The results of the present study are in keeping with the view that in mammals, ZG is the proliferative layer involved in the maintenance of growth of the entire adrenal cortex and with the previous autoradiographic demonstration that ZG is the only adrenocortical layer provided with ETA receptors.

Animals↗

PubMed1997

Angiotensin-II stimulates DNA synthesis in rat adrenal zona glomerulosa cells: receptor subtypes involved and possible signal transduction mechanism.

Using an in situ perfusion technique of isolated left rat adrenal gland, it has been demonstrated that angiotensin-II (ANG-II) increases DNA synthesis in the zona glomerulosa (ZG), but not fasciculata-reticularis cells. The AT1 receptor antagonist DuP753 abolished the effect of ANG-II, while the AT2 receptor antagonist PD 123319 potentiated it. Both Ro31-8220, an inhibitor of protein kinase C (PKC), and tyrphostin-23, an inhibitor of tyrosine kinase (TK), evoked a partial reversal of ANG-II effect, and when added together to the perfusion medium abolished it. In contrast, the phospholipase C inhibitor U-73122 alone was able to induce a complete blockade of ANG-II effect. Neither the phospholipase A2 inhibitor AACOCF3 nor the cyclooxygenase inhibitor indomethacin and the lipoxygenase inhibitor phenidone affected ANG-II-induced stimulation of DNA synthesis, thereby making unlikely the involvement of the arachidonic acid signaling pathways. Our findings suggest that (i) ANG-II stimulates rat ZG cell proliferation acting via AT1 receptors coupled with phospholipase C, which activates both PKC and TK signaling systems; and (ii) the proliferogenic effect of ANG-II is partially counteracted by the activation of the AT2 receptor subtype.

Angiotensin II↗

PubMed1996

Evidence that both ETA and ETB receptor subtypes are involved in the in vivo aldosterone secretagogue effect of endothelin-1 in rats.

Endothelins (ET) are a family of vasoconstrictor peptides, secreted by vascular endothelium, which act through two main subtypes of receptors: ETA and ETB. ET-1 is known to stimulate aldosterone (ALDO) secretion by adrenal zona glomerulosa (ZG), and in vitro its effect was recently found to be exclusively mediated by ETB receptors. In this study the involvement of ETA and ETB in the mediation of the in vivo acute ALDO secretagogue action of ET-1 was investigated by the use of their selective antagonists BQ-123 and BQ-788, respectively. The bolus intraperitoneal administration of ET-1 dose-dependently raised both basal and angiotensin II (ANG II)-enhanced plasma ALDO concentration (PAC) in rats. Both antagonists counteracted the stimulatory effect of ET-1 on basal PAC, and when administered together completely annulled it. Conversely, only BQ-788 reversed the effect of ET-1 on ANG II-enhanced PAC. ET-1 increased systolic blood pressure (BP) in normal rats, but not in animals simultaneously administered ANG II. The hypertensive effect of ET-1 was completely abolished by BQ-123, and not affected by BQ-788. In light of these findings the following conclusions can be drawn: (i) the in vivo ALDO secretagogue action of ET-1 is mediated by both ETA and ETB, this latter subtype of ET receptors playing a major role; and (ii) the mechanism whereby ETA participates in this in vivo effect of ET-1 is indirect, and probably connected with the ET-1-induced rise in BP and adrenal blood flow.

Adrenal Cortex↗

PubMed1996

Adrenomedullin and calcitonin gene-related peptide inhibit aldosterone secretion in rats, acting via a common receptor.

Adrenomedullin (ADM) and calcitonin gene-related peptide (CGRP) did not affect either basal or ACTH-stimulated secretion of a1dosterone and corticosterone by dispersed rat capsular and inner adrenocortical cells, respectively. However, both peptides strongly depressed angiotensin-II (ANG- II)-stimulated a1dosterone production by capsular cells, the minimal effective concentration was 10(-7) M. The inhibitory effect of both ADM and CGRP was reversed by CGRP8-37, a specific CGRP1 receptor antagonist; a complete reversal was obtained with a CGRP8-37 concentration of 10(-6) M. Our findings indicate that ADM and CGRP specifically interfere with the intracellular mechanisms transducing the secretagogue signal of ANG-II, and suggest that the ADM effect is mediated by CGRP receptors

Adrenocorticotropic Hormone↗

PubMed1995

Morphology and function of the adrenal zona glomerulosa of transgenic rats TGR [mREN2] 27: effects of prolonged sodium restriction.

Heterozygous female transgenic rats for the murine Ren-2 gene (TGR) display a high blood pressure, together with a low kidney and high adrenal renin content. The effects of prolonged sodium restriction on the morphology and secretory activity of adrenal zona glomerulosa (ZG) of TGR and their age- and sex-matched Sprague-Dawley control rats (SDR) were investigated. Under basal conditions, TGR had a moderately hypertrophic ZG, that showed a significantly higher secretion of 18-hydroxylated (18OH) steroids: 18-hydroxy-11-deoxycorticosterone (18OH-DOC), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO); ZG cells of TGR showed angiotensin II (AII)-binding site concentrations and ALDO secretory responses to AII similar to those of SDR ZG cells. Prolonged sodium restriction increased plasma ALDO level in both SDR and TGR, and significantly raised the volume of ZG. ZG hypertrophy was due to the increase in both the number and average volume of its parenchymal cells. The secretion of 18OH-steroids was markedly enhanced in both groups of rats; however, in TGR this rise was exclusively due to increases of 18OH-DOC and 18OH-B, while in SDR also ALDO production was enhanced. The yield of non-18OH-steroids was not affected. 11-Dehydrocorticosterone production was not changed in SDR, but doubled in TGR. ZG cells of sodium-restricted SDR and TGR displayed similar increases in their AII-binding site concentration and ALDO secretory response to AII. In conclusion, our present findings confirm that TGR possess a hypertrophic ZG and an elevated secretory capacity o 18OH-steroids, but show only slight differences in ZG and ZG-cell responses to prolonged sodium deprivation.

Animals↗

PubMed1995

Bacterial lipopolysaccharide stimulates glucocorticoid secretion in hypophysectomized rats.

The effect of an i.p. bolus injection of 200 micrograms.kg-1 bacterial lipopolysaccharide (LPS) on the plasma concentrations of ACTH and corticosterone (B) were studied in intact and hypophysectomized/ACTH replaced (Hx) rats. Hormonal blood levels were measured by RIA, 30, 60, 120, 180 and 240 min after the injection. The stress evoked by the vehicle i.p. injection provoked significant rises in ACTH and B blood levels at 30 and 60 min in intact rats, but not in Hx animals. In intact rats, LPS enhanced (over the respective control value) ACTH plasma level at 60, 120 and 180 min, and B plasma concentration at 120, 180 and 240 min. In Hx rats, LPS did not affect ACTH blood level, but raised B plasma concentration at 60, 120 and 180 min. B response to LPS at 120 min was completely annulled, in both intact and Hx rats, by the simultaneous administration of 25 nmol.kg-1 alpha-helical-CRH and corticotropin-inhibiting peptide that are competitive inhibitors of CRH and ACTH, respectively. The hypothesis is advanced that LPS may activate hypothalamo-pituitary adrenal axis in rats, by stimulating not only the central (hypothalamo-pituitary), but also the peripheral (intra-adrenal) branch of the CRH/ACTH system.

Adrenocorticotropic Hormone↗

PubMed1994

Zona glomerulosa of the adrenal gland in a transgenic strain of rat: a morphologic and functional study.

Transgenic rats for the murine Ren-2 gene display high blood pressure, low circulating levels of angiotensin II, and high renin content in the adrenal glands. Moreover, transgenic rats possess an increased aldosterone secretion (maximal from 6 to 18 weeks of age), paralleling the development of hypertension. To investigate further the cytophysiology of the adrenal glands of this strain of rats, we performed a combined morphometric and functional study of the zona glomerulosa of 10-week-old female transgenic rats. Morphometry did not reveal notable differences between zona glomerulosa cells of transgenic and age- and sex-matched Sprague-Dawley rats, with the exception of a marked accumulation of lipid droplets, in which cholesterol and cholesterol esters are stored. The volume of the lipid-droplet compartment underwent a significant decrease when transgenic rats were previously injected with angiotensin II or ACTH. Dispersed zona glomerulosa cells of transgenic rats showed a significantly higher basal aldosterone secretion, but their response to angiotensin II and ACTH was similar to that of Sprague-Dawley animals. Angiotensin II-receptor number and affinity were not dissimilar in zona glomerulosa cells of transgenic and Sprague-Dawley rats. These data suggest that the sustained stimulation of the adrenal renin-angiotensin system in transgenic animals causes an increase in the accumulation in zona glomerulosa cells of cholesterol available for steroidogenesis, as indicated by the expanded volume of the lipid-droplet compartment and the elevated basal steroidogenesis. However, the basal hyperfunction of the zona glomerulosa in transgenic animals does not appear to be coupled with an enhanced responsivity to its main secretagogues, at least in terms of aldosterone secretion.

Adrenocorticotropic Hormone↗

PubMed1994

Evidence that endogenous somatostatin (SRIF) exerts an inhibitory control on the function and growth of rat adrenal zona glomerulosa. The possible involvement of zona medullaris as a source of endogenous SRIF.

The effect of SRIF and its antagonist cyclo(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr magnitude of Bzl)(SRIF-A) were studied in sham-operated and bilaterally adrenalectomized rats bearing ACTH- and angiotensin II (ANG-II)-responsive adrenocortical autotransplants. SRIF-A (10(-5) M) completely annulled SRIF (10(-6) M)-induced inhibition of ANG-II (10(-8) M)-evoked rise in aldosterone (ALDO) secretion by both dispersed zona glomerulosa (ZG) cells and autotransplant slices. A 7-day intraperitoneal infusion with SRIF (0.3 nmol.kg-1.min-1) significantly lowered plasma ALDO concentration (PAC) in both groups of animals, without affecting plasma renin activity and the plasma levels of ACTH and corticosterone. This treatment caused a marked atrophy of adrenal ZG and its parenchymal cells (without inducing any significant change in the zona fasciculata morphology), as well as of ZG-like cells of autotransplants. Isolated ZG cells and autotransplant slices from SRIF-infused rats evidenced a notable decrease in both their basal and maximally ACTH- or ANG-II-stimulated ALDO production. The simultaneous infusion of rats with SRIF-A (3 nmol.kg-1.min-1) completely reversed all these effects of SRIF. The prolonged infusion with SRIF-A alone caused, in sham-operated rats, a marked increase in PAC and a significant hypertrophy of ZG and ZG cells; basal and maximally-stimulated ALDO secretion of dispersed ZG cells was also notably raised. Conversely, SRIF-A infusion did not evoke any appreciable effect in autotransplanted rats. These findings suggest that endogenous SRIF is specifically involved in the negative control of the secretion and growth of the rat adrenal ZG. Since regenerated adrenocortical autotransplants, which are responsive to SRIF but not to SRIF-A infusion, are completely deprived of chromaffin cells, the hypothesis is advanced that adrenal zona medullaris may be the source of endogenous SRIF regulating ZG function.

Adrenal Cortex↗

PubMed1994

Evidence that endogenous vasoactive intestinal peptide (VIP) plays a role in the maintenance of the growth and steroidogenic capacity of rat adrenal zona glomerulosa.

The effects of a 7-day intraperitoneal infusion with VIP (0.03 nmol.kg-1.min-1) and its antagonist [4-Cl-D-Phe6,Leu17]-VIP (VIP-A; 3 nmol.kg-1.min-1) were studied in sham and bilaterally adrenalectomized rats bearing ACTH and angiotensin II (ANG-II)-responsive adrenocortical autotransplants. VIP significantly increased plasma aldosterone (ALDO) concentration (PAC) and lowered plasma renin activity (PRA) in both groups of animals, without affecting plasma levels of ACTH and corticosterone. This treatment caused a marked hypertrophy of adrenal zona glomerulosa (ZG) and its parenchymal cells (without inducing any significant change in the zona-fasciculata morphology), as well as of ZG-like cells of autotransplants. Isolated ZG cells and autotransplant quarters obtained from VIP-infused rats evidenced a notable increase in both their basal and maximally ACTH- or ANG-II-stimulated ALDO secretion. The simultaneous infusion of rats with VIP-A completely reversed all these effects of VIP. The infusion with VIP-A alone caused, in sham-operated rats, a net decrease in PAC, coupled with a rise in PRA, and a marked atrophy of ZG and ZG cells; basal and maximally stimulated ALDO secretion of dispersed ZG cells was also significantly lowered. Conversely, VIP-A did not evoke any appreciable effect in autotransplanted rats. These findings suggest that endogenous VIP is specifically involved in the maintenance of the growth and secretory capacity of rat adrenal ZG. Since regenerated adrenocortical autotransplants, which are responsive to VIP but not to VIP-A infusion, are completely deprived of chromaffin cells, the hypothesis is advanced that adrenal medulla may be the source of endogenous VIP regulating ZG function.

Adrenocorticotropic Hormone↗

PubMed1994

Age-dependent changes in the function and morphology of mitochondria of rat adrenal zona fasciculata.

The function and morphology of adrenal zona-fasciculata (ZF) mitochondria were studied in 4-, 10- and 16-month-old rats, since in this species ageing causes a marked decline in glucocorticoid secretion coupled with high levels of circulating ACTH. Dispersed intact ZF cells displayed a significant age-dependent impairment of their basal pregnenolone (PREG) secretion, but isolated ZF mitochondria showed an increased capacity to convert cholesterol to PREG (the first rate-limiting step of steroid synthesis). These data are in keeping with the contention that the age-related deficit of rat ZF secretion is located prior to the activity of intramitochondrial cholesterol side-chain cleaving enzymes (cytochrome-P450scc). Stereology showed a notable age-dependent increase in the number of mitochondria per unit cell-volume, coupled with a marked decrease in their average volume. The width of the mitochondrial intermembrane space remained unchanged, but its average volume strikingly decreased. This last finding fits well with the enhanced capacity of mitochondria to produce PREG, since intermembrane space is an aqueous barrier to the translocation of free cholesterol from the outer membrane to the cristae, where cytochrome-P450scc is located. In conclusion, the hypothesis is advanced that all these age-related functional and morphological mitochondrial changes are an ACTH-dependent compensatory response enabling ZF cells to partially counteract their decreased glucocorticoid secretory capacity, which in turn is due to the impaired utilization of intracytoplasmic stores of cholesterol esters.

Aging↗

PubMed1993

Evidence that an extrahypothalamic pituitary corticotropin-releasing hormone (CRH)/adrenocorticotropin (ACTH) system controls adrenal growth and secretion in rats.

Within two weeks, hypophysectomy induced in rats a striking decrease in the level of circulating ACTH (the concentration of which was at the limit of sensitivity of our assay system), coupled with a net reduction in the plasma corticosterone concentration and an evident adrenal atrophy. Zona fasciculata, the main producer of glucocorticoids, was decreased in volume, due to a lowering in both the number and average volume of its parenchymal cells. Subcutaneous ACTH infusion (0.1 pmol.min-1), administered during the last week following hypophysectomy, restored the normal blood level of ACTH and completely reversed all effects of hypophysectomy on the adrenals. Subcutaneous infusion for one week with alpha-helical-CRH or corticotropin-inhibiting peptide (1 nmol.min-1), which are competitive inhibitors of CRH and ACTH, evoked a further significant lowering of plasma corticosterone concentration and markedly enhanced adrenal atrophy in hypophysectomized rats. These findings strongly suggest that an extrahypothalamic pituitary CRH/ACTH system may be involved in the maintenance of the growth and steroidogenic secretory activity of the rat adrenal cortex.

Adrenal Glands↗

PubMed1992

The effects of ageing on the morphology and function of the zonae fasciculata and reticularis of the rat adrenal cortex.

The morphological counterpart of the well-known age-dependent marked impairment of glucocorticoid secretion of rat adrenals was investigated by use of morphometric techniques. For this purpose 4-, 8-, 16- and 24-month-old rats were studied. Despite the notable lowering of both basal and ACTH-stimulated production of corticosterone by collagenase-dispersed inner adrenocortical cells, ACTH and corticosterone plasma concentrations displayed significant increases with ageing. Zona fasciculata (ZF) and zona reticularis (ZR) showed a notable hypertrophy in aged rats, which was due to rises in both the average volume and number of their parenchymal cells. The hypertrophy of ZF and ZR cells was in turn associated with increase in the volume of the mitochondrial compartment and proliferation of smooth endoplasmic reticulum, i.e., the two organelles involved in steroid-hormone synthesis. All these morphologic changes, conceivably due to the chronic exposure to high levels of circulating ACTH, are interpreted as a response enabling ZF and ZR to compensate for their age-dependent lowering in glucocorticoid secretion. Stereology also demonstrated that ZF and ZR cells underwent a striking age-related lipid-droplet repletion. Lipid droplets are the intracellular stores of cholesterol esters, the obligate precursors of steroid hormones in rats. This finding is in keeping with the contention that the mechanism underlying the age-dependent decline in rat-adrenal glucocorticoid secretion mainly involves impairments of the utilization of intracellular cholesterol previous to its intramitochondrial transformation to pregnenolone.

Adrenocorticotropic Hormone↗

PubMed1992

Effects of galanin on the secretory activity of the rat adrenal cortex: in vivo and in vitro studies.

Galanin, a 28-amino-acid peptide originally isolated from pig intestine, was found to cause dose-dependent rises in the plasma concentration of corticosterone in hypophysectomized rats and in both basal and submaximally ACTH-stimulated in vitro corticosterone production by adrenal quarters and isolated zona fasciculata/reticularis cells. These findings indicate that galanin exerts a direct glucocorticoid secretagogue effect on the inner adrenocortical zones and suggest that galanin, high concentrations of which are contained in adrenal chromaffin cells, may be included in that group of regulatory peptides, by way of which adrenal zona medullaris is thought to exert a paracrine control on the function of the zona corticalis. Galanin was also found to increase the plasma level of aldosterone in hypophysectomized rats in a dose-dependent manner without inducing changes in natremia, kalemia, plasma renin activity, or ACTH plasma concentration. Galanin did enhance both basal aldosterone output and that following submaximal ACTH or angiotensin II stimulation aldosterone output from adrenal quarters, but not from isolated zona glomerulosa cells. This last, rather unexpected, result suggests that galanin exerts an indirect mineralocorticoid secretagogue action, which seems to require the structural integrity of the adrenal cortex and the presence of the adrenal medulla. The hypothesis is advanced that galanin may control the release of some medullary peptides, which in turn may affect mineralocorticoid secretion of the zona glomerulosa in a paracrine manner.

Adrenal Cortex↗