Biomedical subjects

Ludwik K Malendowicz

Publications and source records attributed to Ludwik K Malendowicz.

At least 19 recordsLinked to original sources

PubMed2026

Single-cell spatial transcriptomic atlas of the mouse adrenal gland reveals sexual dimorphism in steroidogenic enzyme and hormone receptor expression.

The adrenal cortex shows sexual dimorphism in structure and function. We analysed adrenal glands from 7-week-old male and female BALB/c mice using Visium HD with Cellpose 3 segmentation, comprising 236,077 cells across eleven populations, including four cortical zones. Using curated marker-gene-based zonal annotation, we focused on steroidogenic enzymes and hormone receptors, complementing our companion study based on the same primary dataset. The X-zone was nearly absent in males but prominent in females. Females showed higher Hsd3b1 expression across cortical zones and higher Cyp11b1 expression in outer cortical compartments. The strongest sex difference involved Srd5a2, with markedly higher expression in male zona fasciculata (inner: 77.1% vs. 28.9%), independently supported by RNAscope and immunohistochemistry. Mc2r and Mrap showed discordant spatial distributions, with limited co-expression, suggesting potential MC2R-independent MRAP roles. Agtr1a dominated angiotensin II receptor expression in zona glomerulosa without major sex differences, providing a zone-resolved reference for adrenal sexual dimorphism.

Adrenal cortex↗

PubMed2007

Galanin enhances corticosterone secretion from dispersed rat adrenocortical cells through the activation of GAL-R1 and GAL-R2 receptors coupled to the adenylate cyclase-dependent signaling cascade.

Galanin is a regulatory peptide, which acts via three subtypes of receptors, named GAL-R1, GAL-R2 and GAL-R3. Reverse transcription-polymerase chain reaction demonstrated the expression of GAL-R1 and GAL-R2, but not GAL-R3 mRNAs in dispersed rat adrenal zona fasciculata-reticularis (inner) cells. The immuno-blockade of GAL-R1 and GAL-R2, but not GAL-R3, decreased the binding of [3H]galanin to dispersed cells, a complete inhibition being obtained only by the simultaneous blockade of both receptor subtypes. Galanin stimulated corticosterone and cyclic-AMP release from dispersed inner rat adrenocortical cells, while inositol triphosphate production was not affected. Again these responses to galanin were reversed by both the GAL-R1 and GAL-R2, but not the GAL-R3 immuno-blockade. The adenylate cyclase inhibitor SQ-22536 and the protein kinase (PK) A inhibitor H-89 abolished the corticosterone response of dispersed cells to galanin, while the phospholipase C inhibitor U-73122 and the PKC inhibitor calphostin-C were ineffective. We conclude that rat inner adrenocortical cells express GAL-R1 and GAL-R2 as mRNA and protein, and galanin stimulates corticosterone secretion acting via these receptor subtypes which are both coupled to the adenylate cyclase/PKA-dependent signaling pathway.

Adenylyl Cyclases↗

PubMed2007

Effects of neuropeptides B and W on the rat pituitary-adrenocortical axis: in vivo and in vitro studies.

Neuropeptides (NP) B and W are hypothalamic peptides involved in the regulation of feeding and neuro-endocrine axes. Evidence has been provided that NPB and NPW act on both the central and the peripheral branches of the rat hypothalamic-pituitary-adrenocortical axis, and we carried out in vivo and in vitro studies to gain insight into this topic. Reverse transcription-polymerase chain reaction showed the expression of NPB, NPW and their receptors in both adrenal cortex (zonae glomerulosa and fasciculata-reticularis) and adrenal medulla, where immunocytochemistry also detected the presence of abundant NPB- and NPW-immunoreactivity. The acute subcutaneous administration of NPB (0.5 or 1.5 nmol/100 g) did not alter ACTH plasma concentration, while that of NPW (1.5 nmol/100 g) decreased it. Neither NPB nor NPW affected the blood level of aldosterone, while both peptides (0.5 nmol/100 g) raised that of corticosterone. NPB (10(-6) M) lowered ACTH-stimulated aldosterone secretion, and basal and ACTH-stimulated corticosterone production from adrenal quarters containing both cortical and medullary tissues. NPW (10(-6) M) enhanced basal aldosterone secretion from adrenal quarters, and the effect was suppressed by the beta-adrenoceptor antagonist l-alprenolol (10(-5) M). NPW did not affect corticosterone production. Collectively, our findings allow us to draw the following tentative conclusions: i) ACTH-independent extra-adrenal mechanism(s) are operative in vivo, by which NPB and NPW stimulate adrenal glucocorticoid, but not mineralocorticoid secretion; ii) in vitro the interaction of NPB with adrenal medulla activates unknown mechanism(s) hampering adrenocortical steroidogenic machinery; and iii) NPW stimulates in vitro aldosterone secretion by enhancing the release of medullary catecholamines, which in turn activate beta-adrenoceptors located on zona glomerulosa cells.

Adrenal Cortex↗

PubMed2006

Down-regulation of the beacon gene expression in the regenerating rat adrenal cortex.

Beacon, a hypothalamic peptide involved in the regulation of food intake, has been recently shown to be expressed in the adrenal cortex, and to inhibit its secretion and growth. To further characterize the role of beacon in the control of adrenal growth, we investigated the level of beacon gene expression in the regenerating rat adrenal cortex. Conventional reverse transcription-polymerase chain reaction (PCR) and immunocytochemistry demonstrated the expression of beacon mRNA and protein in the adrenals at both days 5 and 8 of regeneration after enucleation and contralateral adrenalectomy. Semiquantitative real time-PCR revealed a net down-regulation of beacon mRNA in the regenerating glands, as compared to the intact adrenal cortex of sham-operated animals. Beacon gene expression was higher at day 8 than at day 5 of regeneration. Mitotic index, as assayed by the stachmokinetic method with vincristin, was negligible in the intact adrenal, but greatly elevated in regenerating gland, with a higher index found at day 5 than at day 8 after surgery. Taken together our findings indicate that the level of beacon gene expression is inversely correlated with the proliferative activity of adrenocortical cells, and suggest that beacon might act as an endogenous inhibitor of adrenocortical growth in the rat.

Adrenal Cortex↗

PubMed2006

Accumulation of steroidogenic acute regulatory protein mRNA, and decrease in the secretory and proliferative activity of rat adrenocortical cells in the presence of proteasome inhibitors.

Sporadic findings indicate that proteolysis may affect steroid secretion in rat ovary granulosa cells. We examined the effects of the proteasome inhibitors MG115 and MG101 on the in vitro secretion and growth of rat adrenocortical cells. MG115 and/or MG101 decreased within 120 min the aldosterone and corticosterone secretion from freshly dispersed zona glomerulosa and zona fasciculata-reticularis (ZF/R) cells. After a 24-h incubation MG115 alone or with MG101 lowered corticosterone production and enhanced proliferation rate of cultured ZF/R cells, while MG101 was per se ineffective. Real-time polymerase chain reaction demonstrated that MG101 decreased steroidogenic acute regulatory protein (StAR) mRNA in cultured cells. MG115 was per se ineffective, but when added together with MG101 evoked a marked rise in StAR mRNA content. In light of the present findings, we conclude that i) protein breakdown by proteasomes is required for the maintenance of a normal secretory and proliferative activity of freshly dispersed or cultured rat adrenocortical cells; and ii) in long-term experiments, great caution must be taken in correlating StAR mRNA content and steroidogenic capacity.

Adrenal Cortex↗

PubMed2006

Urotensin-II and UII-receptor expression and function in the rat adrenal cortex.

Urotensin-II (UII) is a potent hypertensive peptide, which has been recognized as an endogenous ligand of the G protein-coupled receptor (GPR)-14, now named UT-R. Real-time PCR demonstrated the expression of UII and UT-R mRNAs in both dispersed and in vitro cultured rat adrenocortical cells. UII concentration-dependently decreased basal, but not ACTH-stimulated, corticosterone secretion from cultured adrenocortical cells, and the effect was abolished by the UT-R antagonist Palosuran. UII did not affect the proliferation rate of cultured cells. Taken together, these findings suggest that UII may be included in the group of peptides (adrenomedullin, atrial natriuretic peptide, neurotensin and beacon), that, acting in an autocrine-paracrine manner, are involved in the inhibitory tuning of adrenocortical secretion.

Adrenal Cortex↗

PubMed2006

Effects of some endocrine disruptors on the secretory and proliferative activity of the regenerating rat adrenal cortex.

The effects of some endocrine disruptors that possess estrogen-like activity on the secretion and growth of regenerating rat adrenal cortex have been investigated in ovariectomized (OVX) and sham-OVX rats. As reference groups, dexamethasone (Dx)-administered sham-OVX and 17beta-estradiol-administered OVX animals were used. Dx, estradiol and endocrine disruptors were subcutaneously injected daily at a dose of 3 nmoles/100 g for 10 consecutive days after surgery, and adrenal enucleation was performed on day 5 of the experiment. Dx and genistein significantly decreased corticosterone plasma concentration (as measured by RIA) in sham-OVX rats with regenerating adrenals, while other disruptors (eusolex, procymidone, linurone, resveratrol, bisphenol-A and and silymarin) were ineffective. Mitotic index (as assayed by the stachmokinetic method with vincristine) was not changed by either Dx or disruptors. Estradiol significantly increased and genistein significantly lowered corticosterone blood level in OVX rats; similar effects were induced in the mitotic index of regenerating adrenals, but the changes were not significant. Eusolex increased the mitotic index, without altering the level of circulating corticosterone. Collectively, our findings allow us to conclude that, of the endocrine disruptors tested, only genistein is able to suppress the secretory activity of regenerating adrenal cortex, this Dx-like effect being apparently unrelated to its estrogen-like activity, and only eusolex enhances the proliferation rate of regenerating adrenal, the effect being conceivably connected with its estrogen-like activity.

Adrenal Cortex↗

PubMed2006

Effects of proadrenomedullin N-terminal 20 peptide on the rat pituitary-adrenocortical axis under basal and stressful conditions.

Proadrenomedullin N-terminal 20 peptide (PAMP) derives, along with adrenomedullin (AM), from prepro-AM. AM has been reported to modulate the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and this study aimed at ascertaining whether PAMP exerts similar effects. PAMP was subcutaneously administered to non-stressed and stressed rats, and the plasma concentrations of ACTH and corticosterone were measured by radioimmune assay. In non-stressed rats, PAMP raised ACTH and corticosterone blood levels at 60 min, and ACTH plasma concentration at 120 min. Ether and cold stresses increased the plasma levels of both ACTH and corticosterone, and PAMP dampened HPA axis response to cold stress, without affecting that to ether stress. The conclusion is drawn that PAMP i) stimulates rat HPA axis, through a mechanism similar to that of ether stress; and ii) interferes with the neural pathways involved in the cold stress-induced activation of HPA axis.

Adrenocorticotropic Hormone↗

PubMed2006

Estradiol and resveratrol stimulating effect on osteocalcin, but not osteonectin and collagen-1alpha gene expression in primary culture of rat calvarial osteoblast-like cells.

Evidence is available that some endocrine disruptors, acting as selective estrogen receptor modulators (SERMs), interfere with osteoblast differentiation and function. Therefore, we investigated whether 17beta-estradiol, bisphenol-A (BSP), silymarin, genistein, resveratrol, procymidone, linurone and benzophenone-3 (BP3) modulate differentiation of rat calvarial osteoblast-like (ROB) cells in primary in vitro culture. Disruptors were added at day 18 of culture and cells were harvested 48 h later. Real time-PCR revealed that estradiol and resveratrol enhanced osteocalcin mRNA expression in ROB cells, while other disruptors were ineffective. The expression of osteonectin and collagen-1alpha was not affected by any disruptor. Estradiol, resveratrol, genistein and BSP stimulated the proliferative activity of ROB cells. In contrast, procymidone and linurone inhibited the proliferative activity, and silymarin and BP3 were ineffective. The conclusion is drawn that i) only resveratrol is able, like estradiol, to stimulate the specialized functions of ROB cells, and ii) the proliferative activity of ROB cells is more sensitive to endocrine disruptors, some of which could probably act via a mechanism independent of their SERM activity.

Animals↗

PubMed2006

Neuromedin U receptor 1 expression in the rat endocrine pancreas and evidence suggesting neuromedin U suppressive effect on insulin secretion from isolated rat pancreatic islets.

Neuromedin U (NmU) is a regulatory peptide found in significant concentrations in both the brain and gut of the rat and is named according to its ability to powerfully contract the uterus. Two types of NmU receptors were recently identified and subsequent studies evidenced NmU involvement in the regulation of energy homeostasis. Such a role of neuromedin U suggests that a polypeptide may also be involved in the regulation of adipoinsular axis function. Therefore in the present study we examined the expression of NmU receptors in pancreatic islets using RT-PCR and Western blotting analysis. We also investigated the role of NmU in regulation of insulin secretion in vitro using isolated pancreatic islets. We have confirmed that NmUR1 but not NmUR2 is specifically expressed in isolated rat pancreatic islets. In all tested doses (1, 10, 100 nmol/l) NmU dose- dependently decreased insulin output by isolated pancreatic islets. These inhibitory effects of NmU on insulin secretion may suggest the involvement of NmU in regulating the pancreatic branch of adipoinsular axis function. Thus, NmU can be included in that group of anorectic peptides, which are also involved in the regulation of insulin secretion.

Animals↗

PubMed2006

Expression of neuropeptides B and W and their receptors in endocrine glands of the rat.

Neuropeptides B and W (NPB and NPW) have been identified as endogenous ligands of the G protein-coupled receptors (GPR) 7 and 8, which in humans are expressed in the hypothalamus and probably involved in the regulation of energy homeostasis and feeding behavior. GPR8 is absent in the rat, where the GPR8-like receptor (GPR8-LR) has been described. Reverse transcription-polymerase chain reaction detected the expression of NPB, NPW, GPR7 and GPR8-LR mRNAs in the hypothalamus, anterior pituitary, thyroid and parathyroid glands, pancreatic islets, adrenal glands, ovary and testis of the rat. Immunocytochemistry demonstrated the presence of NPB and NPW immunoreactivities in these same glands. Radioimmune assay showed that the bolus intraperitoneal injection of 2 nmol/100 g NPB or NPW raised the plasma levels of parathyroid hormone, corticosterone and testosterone. NPB also increased the blood concentration of thyroxine, and NPW that of ACTH and estradiol. Taken together, these findings allow us to suggest that NPB and NPW play a role in the autocrine-paracrine functional regulation of the endocrine system in the rat.

Animals↗

PubMed2006

Endocrine disruptors and rat adrenocortical function: studies on freshly dispersed and cultured cells.

The effects of four endocrine disruptors: resveratrol, diphenylolpropane (bisphenol-A; BSP), benzophenone-3 (BP3) and silymarin on the secretory and proliferative activity of rat adrenocortical cells were investigated in vitro. Resveratrol and BP3 acutely increased basal corticosterone secretion from freshly dispersed adrenocortical cells, and resveratrol and BSP enhanced ACTH-stimulated cells. The 24-h exposure to resveratrol and BP3 increased basal corticosterone production from cultured adrenocortical cells, while ACTH-stimulated secretion was increased only by resveratrol. BSP was ineffective, while silymarin decreased basal, but not ACTH-stimulated secretion. The proliferative activity of the cultured adrenocortical cells was unaffected by the tested disruptors. In conclusion, the in vitro direct effect of endocrine disruptors on adrenocortical steroidogenesis displays a great variability, which seems to depend not only on their chemical nature, but also on their dose and the duration of the exposure of the studied cells.

Adrenal Cortex↗

PubMed2005

Orexins stimulate glucocorticoid secretion from cultured rat and human adrenocortical cells, exclusively acting via the OX1 receptor.

Orexins A and B are hypothalamic peptides, that act via two subtypes of receptors, named OX1-R and OX2-R. Rat and human adrenal cortexes are provided with both OX1-R and OX2-R, and we have previously shown that orexin-A, but not orexin-B, enhances glucocorticoid secretion from dispersed adrenocortical cells. Since OX1-Rs preferentially bind orexin-A and OX2-Rs are non-selective for both orexins, the hypothesis has been advanced that the secretagogue effect of orexin-A is exclusively mediated by the OX1-R. Here, we aimed to verify this contention and to gain insight into the signaling mechanism(s) underlying the secretagogue effect of orexins using primary cultures of rat and human adrenocortical cells. Reverse transcription-polymerase chain reaction showed that cultured cells, as freshly dispersed cells, expressed both OX1-R and OX2-R mRNAs. Orexin-A, but not orexin-B, concentration-dependently increased corticosterone and cortisol secretion from cultured rat and human adrenocortical cells, respectively. The blockade of OX1-Rs by selective antibodies abrogated the secretagogue effect of orexin-A, while the immuno-blockade of OX2-Rs was ineffective. The glucocorticoid response of cultured cells to orexin-A was annulled by the adenylate cyclase and protein kinase (PK) A inhibitors SQ-22536 and H-89, and unaffected by the phospholipase C and PKC inhibitors U-73122 and calphostin-C. Orexin-A, but not orexin-B, enhanced cyclic-AMP production from cultured cells, and did not alter inositol-3-phosphate release. Collectively, our present results allow us to conclude that orexins stimulate glucocorticoid secretion from rat and human adrenocortical cells, exclusively acting through OX1-Rs coupled to the adenylate cyclase/PKA-dependent signaling cascade.

Adrenal Cortex↗

PubMed2005

Effects of met-enkephalin on cell proliferation in different models of adrenocortical-cell growth.

Met-enkephalin (met-Enk) is an opioid peptide that acts via three main subtypes of receptors referred to as mu (mu)-, delta (delta)- and zeta (zeta)-receptor. While the first two receptor subtypes mediate the classic opioid effects of met-Enk, zeta-receptors are reported to be involved in the non-opioid actions of the peptide, i.e. the inhibitory effect on the cell growth. Despite the fact that met-Enk is known to regulate the function of the hypothalamic-pituitary-adrenal axis acting on both its central and peripheral branches, none is known on the effects of met-Enk on adrenal growth. Hence, we have investigated the effects of met-Enk and its receptor agonists and antagonists on cell proliferation in three different models of rat adrenal growth: i) immature adrenal cortex, ii) regenerating adrenal cortex and iii) primary cultures of adrenocortical cells. In in vivo experiments, rats were given subcutaneous injections of 1 nmol/100 g of the peptides 28, 16 and 4 h before the sacrifice, and proliferative activity was assessed by counting the number of metaphase-arrested cells (after vincristine administration). In in vitro studies, cultured adrenocortical cells were exposed for 48 h to the peptides at a concentration of 10(-6) M, and proliferative activity was measured by the EZ4U method. The blockade of mu- and delta-receptors raised proliferative activity in immature adrenals and decreased it in regenerating glands, and the effects were reversed by mu- and delta-receptor agonists. Naltrexone-induced blockade of all met-Enk receptor subtypes decreased proliferative activity in immature adrenal and raised it in regenerating glands. The exposure to either mu- or delta-receptor agonists and antagonists evoked doubtful or no effects on the proliferative activity of cultured adrenocortical cells. In contrast, met-Enk exerted a marked antiproliferogenic effect that was reversed by naltrexone. Taken together, these findings allow us to draw the following conclusions: i) mu- and delta-receptor activation inhibits the growth of immature adrenals, stimulates adrenal regeneration, and does not affect proliferation of cultured adrenocortical cells; ii) zeta-receptors mediate the growth inhibitory effect of met-Enk on both regenerating adrenals and cultured adrenocortical cells, but unexpectedly their activation stimulates the growth of immature gland; and iii) the effects of mu- and delta-receptor activation in in vivo experiments are probably mediated by extra-adrenal indirect mechanisms.

Adrenal Cortex↗

PubMed2005

Orexins modulate the growth of cultured rat adrenocortical cells, acting through type 1 and type 2 receptors coupled to the MAPK p42/p44- and p38-dependent cascades.

Orexin A and B are hypothalamic peptides that act through two subtypes of receptors named OX1-R and OX2-R. The OX1-R almost exclusively binds orexin-A, whereas OX2-R is non-selective for both orexins. We previously found that rat adrenocortical cells express both orexin-receptor subtypes, and orexin-A stimulates corticosterone secretion from dispersed adrenocortical cells acting via the OX1-R. Here, we examined the possibility that orexins, acting through both their receptor subtypes, modulate the growth of adrenocortical cells. Reverse transcription-polymerase chain reaction showed that rat adrenocortical cells cultured in vitro for four days expressed OX1-R and OX2-R mRNAs. Orexin-A increased the proliferation rate (PR) of cultured cells, while orexin-B lowered it. Using selective antibodies, we demonstrated that OX1-R immuno-blockade reversed the proliferogenic action of orexin-A, causing a sizeable decrease in PR. In contrast, OX2-R immuno-blockade magnified the proliferogenic effect of orexin-A and annulled the antiproliferogenic action of orexin-B. The proliferogenic effect of orexin-A in the presence of OX2-R immuno-blockade was abrogated by the MAPK p42/p44 inhibitor PD-98059, while the antiproliferogenic effect of orexin-A in the presence of OX1-R immuno-blockade was annulled by the MAPK p38 inhibitor SB-203580. Neither inhibitor altered per se the basal PR of cultured cells. Taken together, our present findings allow us to conclude that i) orexins modulate the growth of rat adrenocortical cells cultured in vitro, by exerting both proliferogenic and antiproliferogenic effects, which are mediated by OX1-Rs and OX2-Rs, respectively; and ii) OX1-R and OX2-R growth effects involve the activation of the MAPK p42/p44 and p38 signaling cascades, respectively.

Adrenal Cortex↗

PubMed2005

Evidence that orexins A and B stimulate insulin secretion from rat pancreatic islets via both receptor subtypes.

Orexins are recently identified neuropeptides that appear to play a role in the regulation of energy homeostasis and arousal. They bind to and activate two closely related G protein-coupled receptors (OXR1 and OXR2), previously described as orphans. In this study we examined involvement of orexins in regulation of insulin secretion from rat pancreatic islets utilizing an in situ perfused pancreas and isolated pancreatic islet models. By means of RT-PCR we found that both OXR1 and OXR2 are expressed in rat pancreatic islets. Furthermore, the expression levels of OXR1 were higher than OXR2. In both experimental models applied, orexins A and B (1, 10 and 100 nmol/l) concentration dependently stimulated insulin secretion at two different glucose concentrations (6.66 or 26.4 mmol/l), with orexin A being more potent than orexin B. This study demonstrates that orexins A and B modulate insulin secretion in vitro.

Animals↗

PubMed2005

Arginin-vasopressin regulates proliferative activity of the regenerating rat adrenal cortex.

Enucleation-induced adrenal regeneration is a classic model to investigate adrenocortical proliferation in vivo, which is dependent not only on pituitary ACTH release, but also on various other neural and endocrine signals. Arginin-vasopressin (AVP), mainly acting via V1 receptors, regulates hypothalamic-hypophyseal-adrenal axis function, acting on both its central and peripheral branches. Here, we studied whether endogenous AVP system modulates rat adrenal regeneration. Reverse transcription-polymerase chain reaction (PCR) detected only the mRNAs of V1a and V1b receptors in normal and regenerating adrenals. The expression was very low, and semi-quantitative conventional and real-time PCR showed that it was down-regulated in regenerating adrenals in relation to the time elapsed from enucleation. AVP (three subcutaneous injections 28, 16 and 4 h before sacrifice) raised metaphase index at day 5, but not at day 8 of regeneration. Unexpectedly, both V1-receptor and V2-receptor antagonists increased metaphase index at days 5 and 8 of regeneration. Neither AVP nor AVP-receptor antagonists affected plasma levels of corticosterone in rats bearing regenerating adrenals. It is concluded that AVP, acting via V1 receptors located in adrenals, exerts a stimulating effects on adrenal regeneration. Due to the down-regulation of V1-receptor expression in regenerating adrenals, this effect is very weak and is easily overcome by a tonic inhibitory action of endogenous AVP systems probably involving extra-adrenal indirect mechanisms.

Adrenal Cortex↗

PubMed2005

Differential expression and function of beacon in the rat adrenal cortex and medulla.

Beacon gene is overexpressed in obese rats, and beacon was found to stimulate food intake. Evidence has been recently provided that beacon is also expressed in the endocrine glands of normal rats, including adrenal cortex, of which it appears to regulate secretory activity. To further characterize the role of beacon in the rat adrenals, we investigated the level of beacon expression in the adrenal zona glomerulosa (ZG), zona fasciculata-reticularis (ZF/R) and medulla (AM), and the in vitro secretory responses to beacon[47-73] (hereinafter, beacon) of adrenocortical and adrenomedullary tissues. Real-time polymerase chain reaction revealed similar high levels of beacon mRNA in the ZG and ZF/R, and significantly lower (-80%) levels in AM. Immunocytochemistry showed that the distribution of beacon protein followed that of beacon mRNA. Quantitative high pressure liquid chromatography demonstrated that beacon (5x10(-7) M) reduced by about 56% the in vitro total steroid-hormone production from ZG and ZF/R tissues, without affecting catecholamine secretion from AM specimens. The beacon-induced lowering in the secretory activity of adrenal cortex depended on similar reductions (from 50-64%) in the production of the main adrenocortical hormones (pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone, 18-hydroxy-corticosterone and aldosterone), thereby suggesting an inhibitory action of beacon in the early step of steroidogenesis (i.e. the conversion of cholesterol to pregnenolone). The hypothesis is advanced that beacon is to be considered an autocrine-paracrine negative regulator of mineralo- and glucocorticoid synthesis in the rat adrenal gland.

Adrenal Cortex↗