Introduction: Adrenocortical activity in various species is sensitive to androgens and estrogens. They may affect adrenal cortex growth and functioning either via central pathways (CRH and ACTH) or directly, via specific receptors expressed in the cortex and/or by interfering with adrenocortical enzymes, among them those involved in steroidogenesis. Only limited data on expression of androgen and estrogen receptors in adrenal glands are available.
View Article and Find Full Text PDFNotable sex-related differences exist in mammalian adrenal cortex structure and function. In adult rats, the adrenal weight and the average volume of zona fasciculata cells of females are larger and secrete greater amounts of corticosterone than those of males. The molecular bases of these sex-related differences are poorly understood.
View Article and Find Full Text PDFVSNL1 encodes the calcium-sensor protein visinin-like 1 and was identified previously as an upregulated gene in a sample set of aldosterone-producing adenomas. Recently, by means of microarray studies we demonstrated high expression of Vsnl1 gene in rat adrenal zona glomerulosa (ZG). Only scanty data are available on the role of this gene in adrenal function as well as on regulation of its expression by factors affecting adrenal cortex structure and function.
View Article and Find Full Text PDFEnucleation-induced adrenal regeneration is a highly controlled process; however, only some elements involved in this process have been recognized. Therefore, we performed studies on regenerating rat adrenals. Microarray RNA analysis and QPCR revealed that enucleation resulted in a rapid elevation of expression of genes involved in response to wounding, defense response, and in immunological processes.
View Article and Find Full Text PDFThe enucleation-induced (EI) rapid proliferation of adrenocortical cells is followed by their differentiation, the degree of which may be characterized by the expression of genes directly and indirectly involved in steroid hormone biosynthesis. In this study, out of 30,000 transcripts of genes identified by means of Affymetrix Rat Gene 1.1 ST Array, we aimed to select genes (either up- or downregulated) involved in steroidogenesis in the course of enucleation-induced adrenal regeneration.
View Article and Find Full Text PDFEnucleation-induced rapid proliferation of adrenocortical cells and restoration of adrenals structure requires formation of new blood vessels. The performed studies aimed to select from around 30,000 transcripts, identified by means of Affymetrix(®) Rat Gene 1.1 ST Array, the genes involved in angiogenesis in the course of enucleation-induced adrenal regeneration and to characterize their expression levels in regenerating gland between days 1 and 15 after surgery.
View Article and Find Full Text PDFStudies involving the role of ghrelin (GHREL) in regulating the proliferative activity of various cell types have obtained variable results depending primarily on the experimental model applied. It was recently reported that neither GHREL nor obestatin (OBS) affected the proliferative activity of cultured rat adrenocortical cells. In view of the conflicting results, we investigated the effects of GHREL and OBS on the proliferative activity of rat adrenocortical cells in a model of bilateral enucleation-induced adrenocortical regeneration in the rat.
View Article and Find Full Text PDFNeuromedin-U (NMU) is a brain-gut peptide, which has been previously found to stimulate hypothalamic-pituitary-adrenal axis in the rat and to control the growth of the rat adrenal cortex. The present study aimed to investigate the possible involvement of NMU in the regulation of unilateral adrenalectomy-induced compensatory adrenal growth, a phenomenon known to be neurally mediated. The right adrenal gland of mature female rats was removed, the contralateral gland was then analyzed at 24 and 72h following surgery.
View Article and Find Full Text PDFNeuromedin U (NMU) is a brain-gut peptide involved in the regulation of the hypothalamic-pituitary-adrenal axis and adrenocortical cell proliferation. In this study, we investigated the effects of NMU8 (three subcutaneous injections of 6.0 nmol/100 g, 24, 16 and 8 h before autopsy) on the adrenal glands of rats treated for 2 or 4 days with a low (2 microg/100 g body weight/24 h) or a high (8 microg) dose of adrenocorticotropic hormone (ACTH).
View Article and Find Full Text PDFNeuromedin-U (NMU) is a brain-gut peptide, which has been previously found to stimulate hypothalamic-pituitary-adrenal axis in the rat. Enucleation-induced adrenal regeneration in rats with contralateral adrenalectomy is a well-established model of adrenal growth, that not only depends on the compensatory ACTH hypersecretion, but is also modulated by several regulatory peptides. Hence, we investigated whether NMU may be included in this group of bioactive molecules.
View Article and Find Full Text PDFNeuromedin U (NMU) is a brain-gut peptide, that in the peripheral organs and tissues acts via a G protein-coupled receptor, called NMUR1. Reverse transcription-polymerase chain reaction showed the expression of NMUR1 mRNA in either cortex and medulla or dispersed zona glomerulosa and zona fasciculata-reticularis cells of the immature rat adrenals. Accordingly, immunocytochemistry demonstrated the presence of NMUR1-like immunoreactivity in the cortex and medulla of immature adrenals.
View Article and Find Full Text PDFNeuromedin S (NMS) and neuromedin U (NMU) are regulatory peptides that share the C-terminal amino-acid sequence and act via common G protein-coupled receptors called NMUR1 and NMUR2. Semiquantitative real time-PCR showed that in the rat hypothalamus and testis NMS gene expression was markedly higher than that of the NMU gene, while the reverse occurred in the anterior pituitary and thyroid gland. Low expression of both genes was detected in the thymus, adrenal gland and ovary, whereas in the pancreatic islets only the expression of NMU mRNA was detected.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFEnucleation-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.
View Article and Find Full Text PDFMany lines of evidence indicate that cholecystokinin (CCK) and its receptors, named CCK1-R and CCK2-R, are expressed in the hypothalamo-pituitary-adrenal (HPA) axis, the function of which they acutely stimulate. However, the role of endogenous CCK system in the regulation of HPA axis is still unknown. To address this issue we investigated the effect of the prolonged (6-day) administration of CCK, CCK-R antagonists (CCK-RAs) and pentagastrin (PG), a CCK2-R agonist, on adult rat HPA axis.
View Article and Find Full Text PDFExendin-4 (Ex4) is a potent and long-lasting agonist of glucagon-like peptide-1 (GLP-1), which has been previously found to stimulate pituitary-adrenal axis in the rat. Aim of the present study was to gain insight into the mechanism(s) involved in the Ex4-induced rise in the rat plasma concentrations of ACTH, aldosterone and corticosterone. Preliminary time- and dose-response studies showed that the maximum stimulating effect of Ex4 occurred within 1 or 2 h and at dose ranging from 0.
View Article and Find Full Text PDFGhrelin is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), which was originally isolated from rat stomach. Ghrelin and GHS-R are also expressed in several peripheral tissues, including adrenal glands, and this prompted us to study ghrelin expression and ghrelin-binding site localization in the human adrenal cortex, and the possible effect of this peptide on corticosteroid-hormone secretion. Reverse transcription-polymerase chain reaction (RT-PCR) and radioimmune assay (RIA) showed sizeable expression of ghrelin mRNA and protein in six human adrenal cortexes.
View Article and Find Full Text PDFMany lines of evidence have shown that preproglucagon-derived peptides affect steroid secretion from dispersed adrenocortical cells, and that streptozotocin (STZ)-induced experimental diabetes alters adrenocortical-cell function. Hence, we compared the effects of glucagon, glucagon-like peptide (GLP)-1 and GLP-2 on basal and ACTH-stimulated secretion of dispersed adrenocortical cells from normal and STZ-induced diabetic rats. We also examined the effects of exendins (EX) 3 and 4, because EX4 is known to be a potent and long-lasting agonist of GLP-1 receptors.
View Article and Find Full Text PDFAdrenomedullin (ADM) and its receptors are expressed in the adrenal cortex, where ADM is currently known to inhibit agonist-stimulated aldosterone secretion from zona glomerulosa (ZG), without affecting either basal aldosterone release or the secretory activity of zona fasciculata-reticularis (ZF/R) cells. These functional findings have been obtained using freshly dispersed adrenocortical cells, but evidence has been provided that ADM is able to enhance basal aldosterone secretion from rat capsule-ZG preparations. Hence, we investigated the effect of ADM and ADM22-52, a putative antagonist of ADM receptors, on the secretory activity of rat adrenal cell cultured in vitro for 72 h.
View Article and Find Full Text PDFAdrenomedullin (AM) is a hypotensive peptide, which derives from the proteolytic cleavage of pro(p)AM, and acts through two subtypes of receptors, named L1-receptor (L1-R) and calcitonin receptor-like receptor (CRLR). CRLR functions as either a calcitonin gene-related peptide (CGRP) receptor or a selective AM receptor depending on which member of a family of receptor-activity-modifying proteins (RAMPs) is expressed: RAMP1 generates CGRP receptors, while RAMP2 and RAMP3 produce AM receptors. Reverse transcription (RT)-polymerase chain reaction (PCR) consistently allowed the detection of pAM and peptidyl-glycine alpha-amidating monooxygenase (the enzyme converting immature AM to the mature peptide) mRNAs in the thymus cortex of immature (10-day-old) rats.
View Article and Find Full Text PDFGhrelin is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), which has been originally isolated from rat stomach. Evidence has been previously provided that adrenal gland possesses abundant ghrelin-displaceable GHS-Rs, but nothing is known about the possible role of ghrelin in the regulation of adrenocortical function. Reverse transcription-polymerase chain reaction demonstrated the expression of ghrelin and GHS-R in the rat adrenal cortex, and high adrenal concentrations of immunoreactive ghrelin were detected by radioimmune assay (RIA).
View Article and Find Full Text PDFEvidence indicates that some regulatory peptides (endothelins, cholecystokinin and VIP) are involved in the control of thymus growth, and we have investigated whether galanin may be included in this group of peptides. In fact, galanin, a 29-amino acid peptide acting through three subtypes of G protein-coupled receptors (GalR1, GalR2 and GalR3), seems to play a role in the control of the immune system. Reverse transcription (RT)-polymerase chain reaction (PCR) allowed the detection of galanin, GalR1 and GalR3 mRNAs in the thymus cortex of immature (20-day-old) rats, while GalR2 expression was very weak or absent.
View Article and Find Full Text PDFEvidence has been provided that adrenomedullin (ADM) stimulates the proliferative activity of adult rat adrenal zona glomerulosa (ZG). However, the selective ADM receptor antagonist ADM(22-52), although being able to block ADM effect, was per se ineffective. In contrast, in the companion paper, we showed that ADM(22-52) depresses the proliferation rate of ZG in 20-day-old rats, suggesting the involvement of endogenous ADM system in adrenal maturation.
View Article and Find Full Text PDFCompelling evidence indicates that the active growth of immature rat adrenal glands is sustained not only by an increased release of pituitary ACTH, but also by other ancillary mechanisms. We investigated whether vasoactive intestinal peptide (VIP), atrial natriuretic peptide (ANP), adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) play a relevant role in these mechanisms. These four regulatory peptides were chosen because previous studies demonstrated that they are expressed in rat adrenals and are able to modulate the secretory activity and growth of zona glomerulosa (ZG), i.
View Article and Find Full Text PDFLeptin is an adipose tissue-secreted hormone, which decreases caloric intake and increases energy expenditure. Some effects of leptin on energy balance seem to be mediated by the hypothalamo-pituitary-thyroid axis. The present study was designed to ascertain whether i) rat thyroid gland expresses the long form of leptin receptor (ObRb) and ii) the prolonged leptin administration (daily subcutaneous injections of 24 nmol/kg leptin for 6 consecutive days) affects thyroid-gland function in this species.
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