scholarly journals Bradykinin B2 Receptor in the Adrenal Medulla of Male Rats and Mice: Glucocorticoid-Dependent Increase With Immobilization Stress

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3729-3738 ◽  
Author(s):  
Regina Nostramo ◽  
Andrej Tillinger ◽  
Lidia Serova ◽  
Richard Kvetnansky ◽  
Esther L. Sabban
Keyword(s):  
Gene Expression ◽  
Adrenal Medulla ◽  
Immobilization Stress ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Mrna Levels ◽  
Stress Exposure ◽  
Bradykinin B2 Receptor ◽  
Catecholamine Biosynthesis ◽  
Catecholaminergic System

Bradykinin, acting via the bradykinin B2 receptor (B2R), is a potent stimulator of adrenomedullary catecholamine biosynthesis and release and likely plays an important role in the adrenomedullary stress response. However, the effects of stress on the expression of this receptor in the adrenal medulla are currently unclear. Here, we examined the changes in adrenomedullary B2R gene expression in male rats in response to single (1 time) and repeated (6 times) exposure to 2 hours immobilization stress (IMO). Immediately after 1 or 6 times IMO, B2R mRNA levels were increased by 9-fold and 7-fold, respectively, and returned to unstressed control levels 3 hours later. This large, but transient, increase in mRNA elicited a doubling of protein levels 3 hours after the stress exposure. Next, the role of the hypothalamic-pituitary-adrenocortical axis in the stress-induced upregulation of B2R gene expression was examined. Treatment with endogenous (corticosterone) and synthetic (dexamethasone) glucocorticoids dose-dependently increased B2R mRNA levels in adrenomedullary-derived PC12 cells. Furthermore, cortisol supplementation at levels mimicking stress exposure elevated B2R mRNA levels in the adrenal medulla of hypophysectomized rats. In response to 1 exposure to IMO, the stress-triggered rise in plasma corticosterone and adrenomedullary B2R mRNA levels was attenuated in CRH-knockout mice and absent in pharmacologically adrenalectomized rats, indicating a requirement for glucocorticoids in the upregulation of B2R gene expression with stress. Overall, the increase in B2R gene expression in response to the stress-triggered rise in glucocorticoids likely enhances catecholamine biosynthesis and release and may serve as an adaptive response of the adrenomedullary catecholaminergic system to stress.

Regulation of nonclassical renin-angiotensin system receptor gene expression in the adrenal medulla by acute and repeated immobilization stress

2015 ◽  
Vol 308 (6) ◽  
pp. R517-R529 ◽  
Author(s):  
Regina Nostramo ◽  
Lidia Serova ◽  
Marcela Laukova ◽  
Andrej Tillinger ◽  
Chandana Peddu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adrenal Medulla ◽  
Immobilization Stress ◽  
Receptor Gene ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Catecholamine Biosynthesis ◽  
Receptor Mrna

The involvement of the nonclassical renin-angiotensin system (RAS) in the adrenomedullary response to stress is unclear. Therefore, we examined basal and immobilization stress (IMO)-triggered changes in gene expression of the classical and nonclassical RAS receptors in the rat adrenal medulla, specifically the angiotensin II type 2 (AT2) and type 4 (AT4) receptors, (pro)renin receptor [(P)RR], and Mas receptor (MasR). All RAS receptors were identified, with AT2 receptor mRNA levels being the most abundant, followed by the (P)RR, AT1A receptor, AT4 receptor, and MasR. Following a single IMO, AT2 and AT4 receptor mRNA levels decreased by 90 and 50%, respectively. Their mRNA levels were also transiently decreased by repeated IMO. MasR mRNA levels displayed a 75% transient decrease as well. Conversely, (P)RR mRNA levels were increased by 50% following single or repeated IMO. Because of its abundance, the function of the (P)RR was explored in PC-12 cells. Prorenin activation of the (P)RR increased phosphorylation of extracellular signal-regulated kinase 1/2 and tyrosine hydroxylase at Ser31, likely increasing its enzymatic activity and catecholamine biosynthesis. Together, the broad and dynamic changes in gene expression of the nonclassical RAS receptors implicate their role in the intricate response of the adrenomedullary catecholaminergic system to stress.

scholarly journals Differential regulation of catecholamine synthesis and transport in rat adrenal medulla by fluoxetine treatment

2015 ◽  
Vol 87 (1) ◽  
pp. 343-350 ◽  
Author(s):  
NATASA SPASOJEVIC ◽  
PREDRAG JOVANOVIC ◽  
SLADJANA DRONJAK
Keyword(s):  
Gene Expression ◽  
Tyrosine Hydroxylase ◽  
Adrenal Medulla ◽  
Norepinephrine Transporter ◽  
Male Rats ◽  
Mild Stress ◽  
Mrna Levels ◽  
Catecholamine Synthesis ◽  
Fluoxetine Treatment ◽  
Chronic Fluoxetine

We have recently shown that chronic fluoxetine treatment acted significantly increasing plasma norepinephrine and epinephrine concentrations both in control and chronically stressed adult male rats. However, possible effects of fluoxetine on catecholamine synthesis and re-uptake in adrenal medulla have been largely unknown. In the present study the effects of chronic fluoxetine treatment on tyrosine hydroxylase, a rate-limiting enzyme in catecholamine synthesis, as well as a norepinephrine transporter and vesicular monoamine transporter 2 gene expressions in adrenal medulla of animals exposed to chronic unpredictable mild stress (CUMS) for 4 weeks, were investigated. Gene expression analyses were performed using a real-time quantitative reverse transcription-PCR. Chronically stressed animals had increased tyrosine hydroxylase mRNA levels and decreased expression of both transporters. Fluoxetine increased tyrosine hydroxylase and decreased norepinephrine transporter gene expression in both unstressed and CUMS rats. These findings suggest that chronic fluoxetine treatment increased plasma catecholamine levels by affecting opposing changes in catecholamine synthesis and uptake.

Effect of different types of stressors on peptide messenger ribonucleic acids in the hypothalamic paraventricular nucleus

1993 ◽  
Vol 128 (6) ◽  
pp. 485-492 ◽  
Author(s):  
Sandra Ceccatelli ◽  
Catello Orazzo
Keyword(s):  
Paraventricular Nucleus ◽  
Immobilization Stress ◽  
Thyrotropin Releasing Hormone ◽  
Hypothalamic Paraventricular Nucleus ◽  
Male Rats ◽  
Mrna Levels ◽  
Corticotropin Releasing Hormone ◽  
Ribonucleic Acids ◽  
Releasing Hormone ◽  
Different Types

Using in situ hybridization we have studied the effects of different types of stressors, such as ether, immobilization, cold and swimming, on the expression of several peptide messenger ribonucleic acids (mRNAs) in the hypothalamic paraventricular nucleus of adult male rats. Paraventricular nucleus sections were hybridized using synthetic oligonucleotide probes complementary to mRNA for corticotropin-releasing hormone, neurotensin, enkephalin and thyrotropin-releasing hormone. A clear upregulation of neurotensin mRNA was seen after ether and, to a lesser extent, after immobilization stress, whereas after the two other stressors neurotensin mRNA was undetectable, as in control rats. An increase in enkephalin mRNA was observed in a selective region of the dorsal part of the medioparvocellular subdivision of the paraventricular nucleus only after ether and immobilization stress. No significant changes were seen in corticotropin-releasing hormone and thyrotropin-releasing hormone mRNA levels in any of the experimental paradigms. The present results show selective changes for various peptide mRNAs in the paraventricular nucleus after various types of stress. Significant effects could be demonstrated only on neurotensin and enkephalin mRNA after ether and immobilization stress. This suggests that adaptive changes in the rate of synthesis, processing and transport of the peptide may develop over a longer period of time.

Differential regulation of FSH and inhibin gene expression and synthesis by testosterone in immature and mature male rats

1993 ◽  
Vol 137 (1) ◽  
pp. 69-79 ◽  
Author(s):  
A. Perheentupa ◽  
M. Bergendahl ◽  
F. H. de Jong ◽  
I. Huhtaniemi
Keyword(s):  
Gene Expression ◽  
Combined Treatment ◽  
Male Rats ◽  
Mrna Levels ◽  
Partial Recovery ◽  
Β Subunit ◽  
Adult Rats ◽  
Testosterone Treatment ◽  
Subunit Mrna ◽  
Immature Rats

ABSTRACT Direct effects of testosterone on gonadotrophins at the pituitary level were studied in intact and castrated immature (age 10 days) and mature (70 days) male rats. Gonadotrophin-releasing hormone action was blocked by treatment with a potent GnRH antagonist, Ac-d-pClPhe-d-pClPhe-d-Trp-Ser-Tyr-d-Arg-Leu-Arg-Pro-d-Ala-NH2CH3COOH (Ant; Organon 30276; 1·0 mg/kg body weight per day) injected subcutaneously. Silicone elastomer capsules were used for the testosterone treatment. Both treatments commenced on the day of orchiectomy and lasted for 7 days. In adult male rats Ant treatment suppressed serum testosterone from 9·5 ± 2·5 (s.e.m.) nmol/l to below the limit of detection (< 0·10 nmol/l; P < 0·01), and the testosterone implants reversed the decrease. Treatment with Ant decreased the pituitary content of FSH-β subunit mRNA in intact and orchiectomized rats to 14% of their respective controls (P < 0·01). These levels were increased to 80–81% of controls (not significant) in both groups by combined treatment with testosterone and Ant. Orchiectomy alone increased FSH-β subunit mRNA by 202% (P < 0·01). In intact immature rats Ant treatment decreased the level of pituitary FSH-β subunit mRNA to 21% (P<0·01), and a partial recovery (P < 0·01) to 42% of controls was observed with combined Ant + testosterone treatment. In contrast, in orchiectomized immature rats, where ANT decreased FSH-β subunit levels to 48% of controls (P < 0·01), testosterone was able to reverse these mRNA levels completely (114% of controls). No evidence for the direct pituitary effects of testosterone were found in the mRNA of the common α or LH-β subunits. In adult rats, the testicular inhibin α and βA subunit mRNA levels were increased (P < 0·01) by Ant + testosterone compared with Ant-treated animals, but there were no differences in serum immunoreactive inhibin between any of the uncastrated adult groups. In intact immature rats, Ant + testosterone treatment increased (P < 0·01) inhibin βA subunit mRNA levels compared with controls and Ant-treated animals. Ant decreased the level of peripheral inhibin immunoreactivity from 8·3 ± 2·0 U/ml to 2·1 ± 0·4 U/ml (P < 0·01) and testosterone reversed it to 5·8 ± 0·6 U/ml (not significant). In conclusion, our observations indicated that testosterone is able to stimulate FSH gene expression and secretion directly in immature and adult rats, but the testosterone response is enhanced at both ages by orchiectomy, even more so in the immature rat. This may be explained by age differences in the contribution of testicular inhibin to the regulation of FSH synthesis and secretion at the pituitary level. Journal of Endocrinology (1993) 137, 69–79

Prepubertal male rats with high rates of germ-cell apoptosis present exacerbated rates of germ-cell apoptosis after serotonin depletion

2016 ◽  
Vol 28 (6) ◽  
pp. 806 ◽  
Author(s):  
Néstor Méndez Palacios ◽  
María Elena Ayala Escobar ◽  
Maximino Méndez Mendoza ◽  
Rubén Huerta Crispín ◽  
Octavio Guerrero Andrade ◽  
...  
Keyword(s):  
Gene Expression ◽  
Germ Cell ◽  
Mrna Expression ◽  
Cell Apoptosis ◽  
Differential Sensitivity ◽  
Male Rats ◽  
Mrna Levels ◽  
Germ Cell Apoptosis ◽  
Expression Of Genes ◽  
Prepubertal Rats

Male germ-cell apoptosis occurs naturally and can be increased by exposure to drugs and toxic chemicals. Individuals may have different rates of apoptosis and are likely to also exhibit differential sensitivity to outside influences. Previously, we reported that p-chloroamphetamine (pCA), a substance that inhibits serotonin synthesis, induced germ-cell apoptosis in prepubertal male rats. Here, we identified prepubertal rats with naturally high or low rates of germ-cell apoptosis and evaluated gene expression in both groups. Bax and Shbg mRNA levels were higher in rats with high rates of germ-cell apoptosis. Rats were then treated with pCA and the neuro-hormonal response and gene expression were evaluated. Treatment with pCA induced a reduction in serotonin concentrations but levels of sex hormones and gonadotrophins were not changed. Rats with initially high rates of germ-cell apoptosis had even higher rates of germ-cell apoptosis after treatment with pCA. In rats with high rates of germ-cell apoptosis Bax mRNA expression remained high after treatment with pCA. On the basis of category, an inverse relationship between mRNA expression of Bax and Bcl2, Bax and AR and Bax and Hsd3b2 was found. Here we provide evidence that innate levels of germ-cell apoptosis could be explained by the level of mRNA expression of genes involved with apoptosis and spermatogenesis.

Effect of blockade of mGluR5 on stress hormone release and its gene expression in the adrenal gland

2014 ◽  
Vol 92 (8) ◽  
pp. 686-692 ◽  
Author(s):  
Michal Pokusa ◽  
Barbora Prokopova ◽  
Natasa Hlavacova ◽  
Aikaterini Makatsori ◽  
Daniela Jezova
Keyword(s):  
Gene Expression ◽  
Adrenal Gland ◽  
Metabotropic Glutamate Receptor ◽  
Glutamate Release ◽  
Catecholamine Release ◽  
Male Rats ◽  
Receptor Subtype ◽  
Mrna Levels ◽  
Hormone Release ◽  
Different Strains

The aim of this study was to verify the presence of metabotropic glutamate receptor subtype 5 (mGluR5) in the adrenal gland of male rats of 2 different strains, and to test the hypothesis that treatment with mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) affects hormone release and adrenal gene expression of mGluR5 under conditions of stress. The results clearly show the gene expression of mGluR5 in the adrenal gland in both the adrenal cortex and medulla. Treatment with the glutamate release inhibitor riluzole (4 mg·(kg body mass)–1·day–1 for 2 weeks) failed to modify mRNA levels of either the mGluR5 or NR1 subunit of the NMDA receptor in the adrenal glands, as measured by real-time PCR. Blockade of mGluR5 with MPEP (1 mg·kg–1 for 4 days) increased corticosterone but not catecholamine release during restraint stress (20 min). Treatment with MPEP had no effect on mRNA levels coding for steroidogenic factors StAR and SF-1, and decreased mGluR5 gene expression in the adrenal gland. In conclusion, mGluR5 is not likely to play a significant role in stress-induced catecholamine release. Pharmacological blockade of mGluR5 has a modest influence on the hypothalamic–pituitary–adrenocortical axis, as reflected in adrenal hypertrophy and increased corticosterone concentrations.

Sexual dimorphism of hepatic 11β-hydroxysteroid dehydrogenase in the rat: the role of growth hormone patterns

1994 ◽  
Vol 143 (3) ◽  
pp. 541-548 ◽  
Author(s):  
S C Low ◽  
K E Chapman ◽  
C R W Edwards ◽  
T Wells ◽  
I C A F Robinson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sexual Dimorphism ◽  
Mrna Expression ◽  
Hydroxysteroid Dehydrogenase ◽  
Male Rats ◽  
Total Daily Dose ◽  
Mrna Levels ◽  
Control Female ◽  
Gh Secretion ◽  
Repressive Effect

Abstract 11 β-Hydroxysteroid dehydrogenase (11β-HSD) catalyses the reversible metabolism of corticosterone to inert 11-dehydrocorticosterone. At least two isoforms exist. 11β-HSD-1, the first to be characterised and the only isoform for which a cDNA has been isolated, is highly expressed in liver, kidney and hippocampus. The activity of 11β-HSD in rat liver is higher in males, due to oestrogen repression of 11β-HSD-1 gene transcription in females. Sexual dimorphism in rodent liver proteins is frequently mediated indirectly via sex-specific patterns of GH release (continuous in females, pulsatile in males). We have now investigated whether this applies to 11β-HSD, using dwarf rats (congenitally deficient in GH) and hypophysectomised animals. 11β-HSD activity and 11β-HSD-1 mRNA expression in liver was significantly lower in control female than male rats (50% and 72% of male levels respectively). These sex differences in the liver were attenuated in dwarf rats, with both males and females showing similar levels of 11 β-HSD activity to control males. Administration of continuous (female pattern) GH to dwarf male rats decreased hepatic 11β-HSD activity (30% fall) and mRNA expression (77% fall), whereas the same total daily dose of GH given in the male (pulsatile) pattern had no effect on hepatic 11 β-HSD in female dwarf rats. Continuous GH also attenuated hepatic 11 β-HSD activity (25% fall) and 11β-HSD-1 mRNA expression (82% fall) in hypophysectomised animals. However, oestradiol itself suppressed hepatic 11β-HSD activity (25% fall) and 11β-HSD-1 mRNA expression (60% fall) in hypophysectomised rats. Renal 11 β-HSD activity showed no sexual dimorphism in control or dwarf rats, although overall activity was lower in dwarf animals. By contrast, 11β-HSD-1 mRNA expression was higher in male than female kidney in both control and dwarf strains. Neither GH pattern had any effect on 11β-HSD activity or 11β-HSD-1 mRNA levels in the kidney of dwarf rats, although continuous GH attenuated 11β-HSD activity (28% fall) and 11β-HSD-1 mRNA expression in kidney (47% decrease) in hypophysectomised animals. Oestradiol attenuated renal 11β-HSD-1 mRNA expression (74% fall) in hypophysectomised rats, but increased enzyme activity (62% rise) in the kidney. None of the manipulations had any effect on hippocampal 11 β-HSD activity or gene expression. These data demonstrate the following. (i) Sexual dimorphism of hepatic 11β-HSD is mediated, in part, via sex-specific patterns of GH secretion acting on 11β-HSD-1 gene expression. (ii) There is an additional direct repressive effect of oestrogen on hepatic 11β-HSD-1. (iii) Other tissue-specific factors are involved in regulating 11β-HSD-1, as neither peripheral GH nor oestrogen have effects upon hippocampal 11β-HSD-1. (iv) The regulation of 11β-HSD-1 mRNA expression in the kidney broadly parallels the liver. The lack of correlation between changes in expression of the 11β-HSD-1 gene and renal 11β-HSD activity reflects the presence of an additional gene product(s) in the kidney, the expression of which is largely independent of GH. Journal of Endocrinology (1994) 143, 541–548

Expression patterns of the c-myc gene in adrenocortical tumors and pheochromocytomas

1997 ◽  
Vol 152 (2) ◽  
pp. 175-181 ◽  
Author(s):  
J Liu ◽  
R Voutilainen ◽  
A I Kahri ◽  
P Heikkilä
Keyword(s):  
Gene Expression ◽  
Adrenal Medulla ◽  
Expression Patterns ◽  
Zona Glomerulosa ◽  
The Other ◽  
Adrenal Tumors ◽  
Zona Fasciculata ◽  
Mrna Levels ◽  
Adrenal Neoplasms ◽  
Adrenocortical Carcinomas

Abstract Abundant c-myc gene expression in neoplasms has been often linked to poor prognosis. As c-myc mRNA is expressed and hormonally regulated in human adrenals, we examined the c-myc gene expression in adrenal tumors by RNA analysis and immunohistochemistry to find out the possible role of c-myc in adrenal neoplasms. The abundant expression of the c-myc gene in normal adrenals was localized to the zona fasciculata and zona reticularis, with much lower expression in the zona glomerulosa and adrenal medulla. In hormonally active adrenocortical carcinomas (n=6) and in virilizing adenomas (n=4), c-myc mRNA levels were approximately 10% of those in normal adrenals (n=11). In contrast, adrenal adenomas from patients with Cushing's (n=4) and Conn's (n=9) syndrome, non-functional adenomas (n=2), adrenocortical hyperplasias (bilateral, n=5; nodular, n=4), and non-functional adrenocortical carcinomas (n=3) expressed c-myc mRNA to the same extent as normal adrenals. The c-myc mRNA abundance in benign adrenal pheochromocytomas (n=19) was similar to that in normal adrenal medulla. However, in malignant adrenal pheochromocytomas (n=6), the average c-myc mRNA levels were approximately threefold that in benign adrenal pheochromocytomas. There was a good correlation between c-myc mRNA expression and immunohistochemical reactivity in both normal and pathological adrenal tissues. Southern blot analysis revealed no amplification or rearrangement of the c-myc gene in any of the adrenal tumors. In conclusion, c-myc expression localized to zona fasciculata and reticularis in normal adrenals. Virilizing adenomas and hormonally active adrenocortical carcinomas expressed c-myc mRNA clearly less than the other adrenal neoplasms and normal adrenal tissue. On the other hand, malignant pheochromocytomas contained more c-myc mRNA than benign ones. Further studies are required to clarify the mechanisms and significance for the distinct expression pattern of the c-myc gene in different adrenal neoplasms. Journal of Endocrinology (1997) 152, 175–181

scholarly journals Regulation of angiotensin II type 2 receptor gene expression in the adrenal medulla by acute and repeated immobilization stress

2012 ◽  
Vol 215 (2) ◽  
pp. 291-301 ◽  
Author(s):  
Regina Nostramo ◽  
Andrej Tillinger ◽  
Juan M Saavedra ◽  
Ashok Kumar ◽  
Varunkumar Pandey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Receptor Gene ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Ang Ii ◽  
Catecholamine Biosynthesis ◽  
Receptor Mrna ◽  
Receptor Gene Expression

While the renin–angiotensin system is important for adrenomedullary responses to stress, the involvement of specific angiotensin II (Ang II) receptor subtypes is unclear. We examined gene expression changes of angiotensin II type 1A (AT1A) and type 2 (AT2) receptors in rat adrenal medulla in response to immobilization stress (IMO). AT2 receptor mRNA levels decreased immediately after a single 2-h IMO. Repeated IMO also decreased AT2 receptor mRNA levels, but the decline was more transient. AT1A receptor mRNA levels were unaltered with either single or repeated IMO, although binding was increased following repeated IMO. These effects of stress on Ang II receptor expression may alter catecholamine biosynthesis, as tyrosine hydroxylase and dopamine β-hydroxylase mRNA levels in PC12 cells are decreased with Ang II treatment in the presence of ZD7155 (AT1 receptor antagonist) or with CGP42112 (AT2 receptor agonist) treatment. Involvement of stress-triggered activation of the hypothalamic–pituitary–adrenocortical or sympathoadrenal axis in AT2 receptor downregulation was examined. Cultured cells treated with the synthetic glucocorticoid dexamethasone displayed a transcriptionally mediated decrease in AT2 receptor mRNA levels. However, glucocorticoids are not required for the immediate stress-triggered decrease in AT2 receptor gene expression, as demonstrated in corticotropin-releasing hormone knockout (Crh KO) mice and hypophysectomized rats, although they can regulate basal gene expression. cAMP and pituitary adenylate cyclase-activating polypeptide also reduced AT2 receptor gene expression and may mediate this response. Overall, the effects of stress on adrenomedullary AT1A and AT2 receptor expression may contribute to allostatic changes, such as regulation of catecholamine biosynthesis.

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