Biomedical subjects

L K Malendowicz

Publications and source records attributed to L K Malendowicz.

At least 55 records · Page 3Linked to original sources

PubMed2000

Effects of leptin on the response of rat pituitary-adrenocortical axis to ether and cold stresses.

Leptin is a hormone mainly secreted by the adipose tissue, which acts through specific receptors widely distributed in the body tissues, including hypothalamopituitary-adrenal axis. We have investigated the effects of a subcutaneous bolus injection of 5 nmol/kg leptin on the pituitary-adrenocortical function in both normal and ether- or cold-stressed rats. Blood concentrations of ACTH, aldosterone and corticosterone were measured by specific RIA 2 or 4 h after the leptin injection. Leptin administration to normal rats resulted in significant rises in the blood levels of ACTH, aldosterone and corticosterone at 2 h, but not at 4 h. Ether and cold stresses markedly increased hormonal blood concentrations at both 2 and 4 h. Leptin magnified ACTH response to ether stress at 2 h, but depressed it at 4 h, and enhanced aldosterone response at 2 h, without affecting corticosterone response. Leptin increased ACTH response to cold stress at both 2 and 4 h, without altering aldosterone and corticosterone responses. In light of these findings, we conclude that: (i) leptin evokes a middle transient activation of the pituitary-adrenocortical axis of rats under basal conditions; (ii) leptin inhibits the ACTH response to ether stress, but magnifies that to cold stress; and (iii) the leptin-evoked changes in the blood level of ACTH are not paralleled by significant modifications in the secretory activity of the adrenal cortex, which probably undergoes a maximal stimulation under stressful conditions.

Adrenal Cortex↗

PubMed2000

Leptin prolonged administration inhibits the growth and glucocorticoid secretion of rat adrenal cortex.

Leptin is an adipose-tissue secreted hormone, that acts to decrease caloric intake and to increase energy expenditure. Some of the leptin effects on the energy balance are known to be mediated by the hypothalamo-pituitary-adrenal (HPA) axis, but the role of this cytokine in the regulation of the growth and steroidogenic capacity of adrenal cortex is still controversial. Therefore, the present study was designed to explore the long-term effects of native leptin[1-147] and its biologically active fragment leptin[116-130] (6 daily subcutaneous injection of 20 nmol/kg) on the rat HPA axis. Leptin[1-147] and leptin[116-130] caused a significant adrenal atrophy, which was mainly due to the decrease in the volume of zona fasciculata (ZF) and in the number of its parenchymal cells. Both leptins provoked a marked drop in the plasma concentrations of ACTH and corticosterone, the main hormone produced by ZF cells. The effects of leptin[116-130] were more intense than those of leptin[1-147]. Leptin[1-147], but not its fragment, evoked a clear-cut rise in the plasma concentration of aldosterone. Collectively, these findings indicate that prolonged leptin administration, by inhibiting pituitary ACTH release, exerts a potent suppressive action on the growth and glucocorticoid secretory capacity of the adrenal cortex in the rat. The mechanism(s) underlying the aldosterone secretagogue action of native leptin remain(s) to be investigated.

Adrenal Cortex↗

PubMed2000

Comparison of the signaling mechanisms involved in the ETB receptor-mediated secretagogue action of endothelin-1 on dispersed zona glomerulosa cells and capsule-zona glomerulosa preparations of the rat adrenal gland.

Endothelin-1 (ET-1) is a hypertensive peptide, which is expressed in the rat adrenal gland, where it stimulates aldosterone secretion from zona glomerulosa (ZG) by activating the ETb receptor subtype. A higher effectiveness of ET-1 has been frequently observed when the integrity of adrenal tissue is preserved. Hence, we compared the aldosterone secretagogue action of ET-1 on dispersed rat ZG cells and capsule-ZG strips. ET-1 concentration-dependently raised aldosterone output by both preparations with similar potency. However, the efficacy of the maximal effective concentration of ET-1 (10-8 M) was about 2.7-fold higher in capsule-ZG strips. The ETb-receptor antagonist BQ-788 (10-7 M) abolished aldosterone response to 10-8 M ET-1 in both ZG preparations, while the ETa receptor antagonist BQ-123 was ineffective. The aldosterone secretagogue action of 10-8 M ET-1 on dispersed ZG cells was concentration-dependently suppressed by the protein kinase (PK) inhibitor calphostin-C. Conversely, both calphostin-C and the nitric oxide (NO) synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) evoked a concentration-dependent partial reversal of the aldosterone response to 10-8 M ET-1 of capsule-ZG strips. The NO donor L-arginine enhanced basal aldosterone yield of capsular strips, but not dispersed ZG cells. The PKA, cyclooxygenase and lipoxygenase inhibitors H-89, indomethacin and phenidone, as well as the beta-adrenoceptor antagonist l-alprenolol, were ineffective. Collectively, these findings allow us to conclude that in the rat i) the ETb receptor-mediated PKC activation is the main signaling mechanism involved in the direct stimulatory effect of ET-1 on ZG cells; and ii) the higher responsiveness of capsular strips to ET-1 may be accounted for by the ETb receptor-mediated release by stromal elements of NO, which in turn increases aldosterone secretion from ZG cells in a paracrine manner.

Adrenal Glands↗

PubMed1999

Effects of glucagon and glucagon-like peptide-1 on glucocorticoid secretion of dispersed rat adrenocortical cells.

The effects of glucagon and glucagon-like peptide-1 (GLP-1) on the secretory activity of rat adrenocortical cells have been investigated in vitro. Neither hormones affected basal or agonist-stimulated aldosterone secretion of dispersed rat zona glomerulosa cells or basal corticosterone production of zona fasciculata-reticularis (inner) cells. In contrast, glucagon and GLP-1 partially (40%) inhibited ACTH (10(-9) M)-enhanced corticosterone secretion of inner cells, maximal effective concentration being 10(-7) M. The effect of 10(-7) M glucagon or GPL-1 was suppressed by 10(-6) M Des-His1-[Glu9]-glucagon amide (glucagon-A) and exendin-4(3-39) (GPL-1-A), which are selective antagonists of glucagon and GLP-1 receptors, respectively. Glucagon and GLP-1 (10(-7) M) decreased by about 45-50% cyclic-AMP production by dispersed inner adrenocortical cells in response to ACTH (10(-9) M), but not to the adenylate cyclase activator forskolin (10(-5) M). Again this effect was blocked by 10(-6) M glucagon-A or GLP-1-A. The exposure of dispersed inner cells to 10(-7) M glucagon plus GLP-1 completely suppressed corticosterone response to ACTH (10(-9) M). However, they only partially inhibited (by about 65-70%) both corticosterone response to forskolin (10(-5) M) or dibutyryl-cyclic-AMP (10(-5) M) and ACTH (10(-9) M)-enhanced cyclic-AMP production. Quantitative HPLC showed that 10(-7) M glucagon or GLP-1 did not affect ACTH-stimulated pregnenolone production, evoked a slight rise in progesterone and 11-deoxycorticosterone release, and markedly reduced (by about 55%) corticosterone secretion of dispersed inner adrenocortical cells. In light of these findings the following conclusion are drawn: (i) glucagon and GLP-1, via the activation of specific receptors, inhibit glucocorticoid response of rat adrenal cortex to ACTH; and (ii) the mechanism underlying the effect of glucagon and GLP-1 is probably two-fold, and involves both the inhibition of the ACTH-induced activation of adenylate cyclase and the impairment of the late steps of glucocorticoid synthesis.

Adrenal Cortex↗

PubMed1999

Gastric inhibitory polypeptide stimulates glucocorticoid secretion in rats, acting through specific receptors coupled with the adenylate cyclase-dependent signaling pathway.

Gastric inhibitory polypeptide (GIP) is a 42-amino acid peptide, belonging to the VIP-secretin-glucagon superfamily, some members of this group are able to regulate adrenocortical function. GIP-receptor mRNA has been detected in the rat adrenal cortex, but investigations on the effect of GIP on steroid-hormone secretion in this species are lacking. Hence, we have investigated the distribution of GIP binding sites in the rat adrenal gland and the effect of their activation in vivo and in vitro. Autoradiography evidenced abundant [125I]GIP binding sites exclusively in the inner adrenocortical layers, and the computer-assisted densitometric analysis of autoradiograms demonstrated that binding was displaced by cold GIP, but not by either ACTH or the selective ACTH-receptor antagonist corticotropin-inhibiting peptide (CIP). The intraperitoneal (IP) injection of GIP dose-dependently raised corticosterone, but not aldosterone plasma concentration: the maximal effective dose (10 nmol/rat) elicited a twofold increase. GIP did not affect aldosterone and cyclic-AMP release by dispersed zona glomerulosa cells. In contrast, GIP enhanced basal corticosterone secretion and cyclic-AMP release by dispersed inner adrenocortical cells in a concentration-dependent manner, and the maximal effective concentration (10(-7) M) evoked 1.5- and 2.4-fold rises in corticosterone and cyclic-AMP production, respectively. GIP (10(-7) M) did not display any additive or potentiating effect on corticosterone and cyclic-AMP responses to submaximal or maximal effective concentrations of ACTH. The corticosterone secretagogue action of 10(-7) M GIP was abolished by the protein kinase A (PKA) inhibitor H-89 (10(-5)M), and unaffected by CIP (10(-6)M). Collectively, these findings indicate that GIP exerts a moderate but statistically significant stimulatory effect on basal glucocorticoid secretion in rats, acting through specific receptors coupled with the adenylate cyclase/PKA-dependent signaling pathway.

Adenylyl Cyclases↗

PubMed1999

Distribution, functional role, and signaling mechanism of adrenomedullin receptors in the rat adrenal gland.

Adrenomedullin (ADM) is a hypotensive peptide, highly expressed in the mammalian adrenal medulla, which belongs to a peptide superfamily including calcitonin gene-related peptide (CGRP) and amylin. Quantitative autoradiography demonstrated the presence of abundant [125I]ADM binding sites in both zona glomerulosa (ZG) and adrenal medulla. ADM binding was selectively displaced by ADM(22-52), a putative ADM-receptor antagonist, and CGRP(8-37), a ligand that preferentially antagonizes the CGRP1-receptor subtype. ADM concentration-dependently inhibited K+-induced aldosterone secretion of dispersed rat ZG cells, without affecting basal hormone production. Both ADM(22-52) and CGRP(8-37) reversed the ADM effect in a concentration-dependent manner. ADM counteracted the aldosterone secretagogue action of the voltage-gated Ca2+-channel activator BAYK-8644, and blocked K+- and BAYK-8644-evoked rise in the intracellular Ca2+ concentration of dispersed ZG cells. ADM concentration-dependently raised basal catecholamine (epinephrine and norepinephrine) release by rat adrenomedullary fragments, and again the response was blocked by both ADM(22-52) and CGRP(8-37). ADM increased cyclic-AMP release by adrenal-medulla fragments, but not capsule-ZG preparations, and the catecholamine response to ADM was abolished by the PKA inhibitor H-89. Collectively, the present findings allow us to draw the following conclusions: (1) ADM modulates rat adrenal secretion, acting through ADM(22-52)-sensitive CGRP1 receptors, which are coupled with different signaling mechanisms in the cortex and medulla; (2) ADM selectively inhibits agonist-stimulated aldosterone secretion, through a mechanism probably involving the blockade of the Ca2+ channel-mediated Ca2+ influx; (3) ADM raises catecholamine secretion, through the activation of the adenylate cyclase/PKA signaling pathway.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1999

Effects of bilateral splanchnic-nerve section and chemical sympathectomy on PACAP38 content in the rat adrenals.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a basic 38-amino acid regulatory peptide contained in the adrenal gland and involved in the control of its secretory activity. Bilateral splanchnic-nerve section caused in the rat a significant decrease in PACAP38 adrenal content and concentration, as measured by RIA. In contrast, chemical sympathectomy, obtained by administering newborn rats with 6-hydroxydopamine, was ineffective. Our findings support the view that splanchnic nerves play an important role in the control of rat adrenal function.

Adrenal Glands↗

PubMed1999

Effects of bilateral splanchnic-nerve section and chemical sympathectomy on PACAP38 content in the rat adrenals.

Adrenal Glands↗

PubMed1999

Bradykinin and pituitary-adrenocortical function in the rabbit: in vitro and in vivo studies.

Bradykinin (BK) is a 9-amino acid peptide, which has been found to affect adrenocortical secretion in the calf and rat. We investigated the in vitro and in vivo effects of BK and its receptor antagonist [D-Arg, (Hyp3,D-Phe7)]-BK (BK-A) on pituitary-adrenocortical function in the rabbit. BK and BK-A raised basal release of aldosterone, but not of corticosterone by dispersed zona glomeralosa and zona fasciculata-reficularis cells, respectively. Both peptides did not affect ACTH-stimulated aldosterone secretion. Conversely, BK concentration-dependently decreased ACTH-stimulated corticosterone production, and BK-A annulled this effect. The bolus intravenous injection of BK did not alter plasma ACTH concentration. However, BK lowered the blood concentration of both aldosterone and corticosterone, as well as the overall production of the two hormones over a period of 90 min after its administration. The simultaneous injection of BK-A blocked these effects of BK. BK-A alone did not evoke any sizeable change in blood hormonal levels. Collectively, these findings allow us to conclude that in rabbits (i) exogenous BK depresses adrenocortical secretion, through a receptor-mediated mechanism, which does not involve the inhibition of pituitary ACTH release-, and (ii) endogenous BK-like peptides do not play a relevant role in the functional regulation of the pituitary-adrenal axis, at least under basal conditions.

Adrenal Cortex↗

PubMed1999

Effects of neurotensin and bombesin on the secretory and proliferative activity of regenerating rat adrenal cortex.

Neurotensin (NT) and bombesin (BM)-like peptides are known to be involved in the regulation of the rat hypothalamo-pituitary-adrenal axis. By using selective NT- and BM-receptor antagonists (NT-A and BM-A, respectively) we investigated whether endogenous NT and BM-like peptides play a role in the control of rat adrenal secretion and growth during enucleation-induced regeneration. At day 5 of regeneration, NT-A did not affect the plasma concentrations of aldosteronc (PAC) and corticosterone (PBC), but at day 8, it raised both PAC and PBC over the respective baseline value; the simultaneous administration of NT abolished this effect of NT-A. BM-A did not alter PAC and PBC at day 5 of regeneration, while at day 8 it enhanced PBC, an effect reversed by BM. NT-A did not alter mitotic index, and BM-A lowered it at both day 5 and day 8 of regeneration, an effect suppressed by the simultaneous administration of BM. Collectively, these findings allow us to draw the following conclusions: 1) endogenous NT and BM-like peptides influence adrenocortical regeneration in rats; 2) NT exerts a tonic inhibitory action on both aldosterone and corticosterone secretion, without affecting cell-proliferation rate; and 3) BM-like peptides exert a tonic suppressive effect on corticosterone production, coupled with a clear-cut stimulating effect on cell proliferation.

Adrenal Cortex↗

PubMed1999

Cholecystokinin, acting through the A receptor subtype, stimulates the proliferative activity of adrenocortical cells and thymocytes in the rat.

Cholecystokinin (CCK) is a multifunctional regulatory peptide, which acts through two main subtypes of receptors, named CCK-A and CCK-B. Evidence indicates that CCK modulates cell proliferation in various tissues in a paracrine manner, and proofs are available of the presence of CCK in both adrenal glands and thymus. Hence, we have investigated the possible mitogenic action of this peptide on these two tissues, by evaluating the /1000 of metaphase-arrested cells after vincristin injection (mitotic index). The systemic administration of CCK (three subcutaneous injections of 20 nmol/kg, 28, 16 and 4 h before the sacrifice) increased the mitotic index in both the outer adrenal and thymus cortexes of immature (20-day-old) rats and the enucleated adrenal gland of adult (2-month-old) animals at day 5 and 8 of regeneration. The simultaneous administration of equimolar doses of a selective CCK-A receptor antagonist blocked the effect of CCK, while a CCK-B antagonist was ineffective. These findings indicate that CCK exerts a marked CCK-A-mediated proliferogenic effect on both adrenal cortex and thymus in the rat, the physiological relevance of which, however, remains to be demonstrated. In fact, the administration of the CCK-A antagonist alone was ineffective, thereby casting doubts on the role played by endogenous CCK in the maintenance and stimulation of adrenal and thymus growth.

Adrenal Cortex↗

PubMed1999

Guanylin: a novel regulatory peptide possibly involved in the control of Ca2+-dependent agonist-stimulated aldosterone secretion in rats.

Guanylin is a 15-amino acid peptide, which activates guanylate cyclase (GC) and plays a major role in the regulation of water and electrolyte secretion by intestinal mucosa. The expression of guanylin prohormone has been recently demonstrated in the rat adrenal gland, and this prompted us to investigate whether guanylin, like other peptides secreted by adrenal medulla, affects the function of the adrenal cortex. Autoradiography demonstrated the presence of [125I]guanylin binding sites in the zona glomerulosa (ZG), but not zona fasciculata-reticularis. Guanylin did not change either basal or ACTH-stimulated steroid secretion of dispersed rat adrenocortical cells, but concentration-dependently (from 10(-10) M to 10(-8) M) inhibited aldosterone response of ZG (capsular) cells to both angiotensin-II (ANG-II) and K+. Guanylin (10(-8) M) blocked the aldosterone secretagogue effect of the Ca2+-channel activator BAYK-8644, and the Ca2+-ionophore ionomycin counteracted the inhibitory action of this peptide on the secretory responses of capsular cells to ANG-II and K+. As expected, guanylin did not affect cyclic-AMP release by capsular cells, but evoked a sizeable increase in cyclic-GMP production. Both the inhibitor of GMP synthase decoyinine and the GC-inhibitor LY-83583, although suppressing cyclic-GMP release, did not affect guanylin-evoked inhibition of K+-stimulated aldosterone secretion. Collectively, these findings allow us to conclude that guanylin: i) inhibits aldosterone secretion of rat ZG cells by interfering with the agonist-induced activation of voltage-gated Ca2+-channels, the stimulation of guanylate cyclase conceivably playing a negligible role; and ii) could be included in that group of regulatory peptides, secreted by medullary chromaffin cells, which are able to counteract an exceedingly high aldosterone secretion.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1999

Mechanisms and receptor subtypes involved in the stimulatory action of endothelin-1 on rat adrenal zona glomerulosa.

Endothelin (ET)-1 is the prototype of a family of 21-amino acid residue hypertensive peptides, acting through two subtypes of receptors, named ETA and ETB. ETs and their receptors are expressed in the adrenal cortex and medulla, and ET-1 enhances both corticosteroid and catecholamine release. ET-1 concentration-dependently (from 10(-11) to 10(-8) M) increased aldosterone secretion of both dispersed rat zona glomerulosa (ZG) cells and adrenal slices containing a core of medullary chromaffin tissue, but the response of the latter preparations was significantly more intense than that of the formers. The stimulatory effect of 10(-8) M ET-1 on dispersed ZG cells was blocked by the ETB-receptor antagonist BQ-788 (10(-7) M), but not by the ETA-receptor antagonist BQ-123 (10(-7) M); conversely, both ET-receptors antagonists counteracted aldosterone response of adrenal slices to ET-1. The -adrenoceptor antagonist l-alprenolol (10(-6) M) did not affect aldosterone response of dispersed ZG cells to ET-1 (10(-8) M), but it significantly lowered that of adrenal slices. l-Alprenolol also counteracted the aldosterone response of adrenal slices to the pure activation of ETB or ETA receptors, as obtained by using the selective ETB-receptor agonist BQ-3020 (10(-8) M) or ET-1 (10(-8) M) plus BQ-788 (10(-7) M). ET-1 concentration-dependently (from 10(-9) to 10(-8)/10(-7) M) stimulated catecholamine release by adrenal slices, and the effect was counteracted by both BQ-123 and BQ-788 (10(-7) M). Collectively, our findings suggest that, when the integrity of adrenal tissue is preserved, a two-fold mechanism underlies the aldosterone secretagogue action of ET-1 in the rat: i) a direct mechanism mediated by ETB receptors located on ZG cells; and ii) an indirect mechanism involving the ETA and ETB receptor-mediated local release of catecholamines, which in turn stimulate ZG cells in a paracrine manner.

Aldosterone↗

PubMed1999

Autocrine-paracrine endothelin system in the physiology and pathology of steroid-secreting tissues.

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Amino Acid Sequence↗

PubMed1998

Pancreatic polypeptide stimulates rat adrenal glucocorticoid secretion by activating the adenylate cyclase-dependent signaling pathway.

Pancreatic polypeptide (PP) concentration-dependently raised basal corticosterone and cyclic-AMP production of dispersed rat zona fasciculata/reticularis adrenocortical cells, maximal effective concentration being 10(-7) M. 10(-7) M PP also significantly enhanced submaximally (10[-12]/10[-11] M), but not maximally (10[-9]/10[-8] M) ACTH-stimulated corticosterone and cyclic-AMP release. Corticosterone responses to PP were abolished by the specific protein kinase A (PKA) antagonist H-89 (10[-5] M). The selective ACTH-receptor antagonist corticotropin-inhibiting peptide (10[-6] M) annulled corticosterone response to 10(-9) M ACTH, but not to 10(-7) M PP. Collectively, our present findings indicate that PP stimulates glucocorticoid secretion of rat adrenal glands, acting through specific receptors coupled, like those of ACTH, with the adenylate cyclase/PKA-dependent signaling pathway.

Adenylyl Cyclases↗

PubMed1998

Endothelin-1, acting via the A receptor subtype, stimulates thymocyte proliferation in the rat.

Endothelins (ETs) are a family of vasoactive peptides widely distributed in the body systems, where they carry out major autocrine/paracrine regulatory functions, acting through two main subtypes of receptors (ETA and ETB). Evidence suggests that ETs play a permissive role in the development of neural crest-derived craniofacial structures, among which the thymus. Therefore, we have investigated whether ETs regulate thymocyte proliferation in the adult rat ET-1 (which binds both ETA and ETB receptors) increased the mitotic index (% of metaphase-arrested cells) in the thymus cortex, while ET-3 (which preferentially binds ETB) and the selective ETB-receptor agonists BQ-3020 and IRL-1620 did not. The ETA-receptor antagonists BQ-123 and BQ-610, but not the ETB-receptor antagonist BQ-788, abolished the ET-1 effect. Moreover, BQ-123 and BQ-610, when administered alone, evoked a significant decrease in the mitotic index. Collectively, these findings clearly indicate that endogenous ETs, through the activation of ETA receptors, are involved in the maintenance and stimulation thymocyte proliferation in the adult rat, thereby playing a possible important role in the modulation of the immune-system functions.

Animals↗

PubMed1998

Acute leptin action on insulin blood level and liver insulin receptor in the rat.

Aim of the study was to investigate acute leptin effect on insulin blood level and liver insulin binding in the rat. The administration of leptin induced time and dose dependent decrease in the insulin level, which was statistically significant in comparison to the control animals 120 min after administration of higher dose of peptide (0.30 +/- 0.05 vs 0.14 +/- 0.01 nmol/l, respectively). Simultaneously, we have shown the attenuation of liver sensitivity to insulin 2 hours after higher leptin dose injection. This phenomenon was caused by the decrease of binding capacity of high affinity insulin receptor sites (HAIR), which was statistically significant after higher leptin dose administration at both time points (0.54 +/- 0.13 vs 0.26 +/- 0.03 and 0.71 +/- 0.12 vs 0.40 +/- 0.05 pmol/mg protein for 1 and 2 h, respectively). The present study provides evidence that leptin, in addition to its inhibitory effect on insulin secretion, acts as a modulator of insulin receptor, through the decrease of binding capacity. It seems legitimate to suggest that leptin-induced decrease of insulin receptor binding capacity may be one of several causes of insulin resistance.

Adipose Tissue↗

PubMed1998

Role of tachykinins in the regulation of the hypothalamo-pituitary-adrenal axis.

Tachykinins are a family of neuropeptides, which act by binding to three main subtypes of G protein-coupled receptors, named NK1, NK2 and NK3. Tachykinins are contained in both nerve fibers and secretory cells of the hypothalamo-pituitary-adrenal (HPA) axis, and evidence indicates that they take part in the functional control of it. Tachykinins involved in this function include substance P (SP), neuropeptide K and its derivative neurokinin A (NKA), and neurokinin B, which preferentially bind to NK1, NK2 and NK3 receptors, respectively. NK1 agonists exert an inhibitory effect on the hypothalamo pituitary CRH/ACTH system, while NK2 and perhaps NK3 agonists stimulate it, thereby controlling the secretion and growth of the adrenal cortex via circulating ACTH. Intra-adrenal tachykinins may also affect the cortex function. Their direct action on adrenocortical cells is doubtful and probably pharmacologic in nature, but several investigations suggest that tachykinins indirectly stimulate the cortex by acting on medullary chromaffin cells, which in turn exert a paracrine control on adrenocortical cells. SP enhances aldosterone production of zona glomerulosa by eliciting catecholamine secretion; neuropeptide K and NKA raise glucocorticoid production of zonae fasciculata and reticularis through the activation of the intramedullary CRH/ACTH system. The relevance of these effects of tachykinins under basal conditions is questionable, although there are indications that SP is involved in the maintenance of a normal growth and steroidogenic capacity of rat zona glomerulosa, and that SP and NKA play an important role in the stimulation of the adrenal growth during the fetal life. In contrast, evidence has been provided that the role of tachykinins, and especially of SP, could become very relevant under paraphysiological (e.g., physical or inflammatory stresses) or pathological conditions (e.g., ACTH-secreting pituitary tumors), when an excess of steroid-hormone production has to be counteracted.

Adrenocorticotropic Hormone↗