Chronic stress induces adrenal hyperplasia and hypertrophy in a subregion-specific manner

2006 ◽  
Vol 291 (5) ◽  
pp. E965-E973 ◽  
Author(s):  
Yvonne M. Ulrich-Lai ◽  
Helmer F. Figueiredo ◽  
Michelle M. Ostrander ◽  
Dennis C. Choi ◽  
William C. Engeland ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Zona Glomerulosa ◽  
Male Rats ◽  
Adrenal Weight ◽  
Zona Fasciculata ◽  
Dna And Rna ◽  
Maximal Output ◽  
Increased Sensitivity ◽  
And Function ◽  
Induced Changes

The adrenal gland is an essential stress-responsive organ that is part of both the hypothalamic-pituitary-adrenal axis and the sympatho-adrenomedullary system. Chronic stress exposure commonly increases adrenal weight, but it is not known to what extent this growth is due to cellular hyperplasia or hypertrophy and whether it is subregion specific. Moreover, it is not clear whether increased production of adrenal glucocorticoid after chronic stress is due to increased sensitivity to adrenocorticotropic hormone (ACTH) vs. increased maximal output. The present studies use a 14-day chronic variable stress (CVS) paradigm in adult male rats to assess the effects of chronic stress on adrenal growth and corticosterone steroidogenesis. Exogenous ACTH administration (0–895 ng/100 g body wt) to dexamethasone-blocked rats demonstrated that CVS increased maximal plasma and adrenal corticosterone responses to ACTH without affecting sensitivity. This enhanced function was associated with increased adrenal weight, DNA and RNA content, and RNA/DNA ratio after CVS, suggesting that both cellular hyperplasia and hypertrophy occurred. Unbiased stereological counting of cells labeled for Ki67 (cell division marker) or 4,6-diamidino-2-phenylindole (nuclear marker), combined with zone specific markers, showed that CVS induced hyperplasia in the outer zona fasciculata, hypertrophy in the inner zona fasciculata and medulla, and reduced cell size in the zona glomerulosa. Collectively, these results demonstrate that increased adrenal weight after CVS is due to hyperplasia and hypertrophy that occur in specific adrenal subregions and is associated with increased maximal corticosterone responses to ACTH. These chronic stress-induced changes in adrenal growth and function may have implications for patients with stress-related disorders.

Thallium Induced Changes in Behavioral Patterns: Correlation With Altered Lipid Peroxidation and Lysosomal Enzyme Activity in Brain Regions of Male Rats

1985 ◽  
Vol 1 (1) ◽  
pp. 81-98 ◽  
Author(s):  
David R. Brown ◽  
Barbara G. Callahan ◽  
Mark A. Cleaves ◽  
Robert A. Schatz
Keyword(s):  
Lipid Peroxidation ◽  
Lysosomal Enzyme ◽  
Brain Regions ◽  
Male Rats ◽  
Patterns Of Behavior ◽  
Low Levels ◽  
Behavioral Sequelae ◽  
Human Poisoning ◽  
And Function ◽  
Induced Changes

The effects of exposures to low levels of heavy metals is a complex and serious problem. Thallium is a metal which produces behavioral sequelae in human poisoning and is potentially hazardous with low level exposures. A test battery is presented which utilizes biochemical and behavioral testing to assess the effects of low levels of thallium on central nervous system chemistry and function in rats. The doses of thallium used (4 and 8 mg/kg) produced no overt signs of behavioral toxicity but did produce dose-related increases in lipid peroxidation and activation of the lysosomal enzyme beta-galactosidase in selected brain regions. At these dose levels, thallium also selectively altered the patterns of behavior. The study suggests that the target regions of thallium in the brain include the cortex, the cerebellum and the brainstem. The dose-response relationships, found for certain pairs of behavioral acts, were correlated with biochemical changes in one or more brain regions.

SOME ASPECTS OF ZONATION AND FUNCTION OF THE ADRENAL CORTEX

1954 ◽  
Vol 10 (3) ◽  
pp. 266-NP ◽  
Author(s):  
I. CHESTER JONES ◽  
A. WRIGHT
Keyword(s):  
Outer Part ◽  
Outer Region ◽  
Pituitary Hormones ◽  
Zona Glomerulosa ◽  
Female Rats ◽  
Zona Fasciculata ◽  
Zona Reticularis ◽  
Male And Female Rats ◽  
Glomerulosa Cells ◽  
And Function

SUMMARY The adrenal of male and female rats with persistent diabetes insipidus showed a prominent zona fasciculata and zona reticularis. The zona glomerulosa was narrow or absent. The results from this and the preceding three papers are here reviewed together. It is concluded that control of salt-electrolyte metabolism cannot be ascribed to the zona glomerulosa. It is probable that the zona fasciculata is reponsible for most of the adrenocortical secretions. The zona glomerulosa is a vegetative back-water of cells, which is able to produce minimal amounts of adrenocortical secretions without stimulation by pituitary hormones, but is only of significance when the latter are absent. Rising amounts of circulating adrenocorticotrophic hormone (ACTH) can transform the zona glomerulosa into actively secreting cells of the zona fasciculata type. After cessation of such activity the zona glomerulosa re-forms, as the amount of ACTH will maintain only a certain volume of zona fasciculata (and zona reticularis) against the rigid limiting inner circumference formed by the medulla; some of the cells derived from the chief area of cell division in the outer part of the zona fasciculata do not mature to cells of the zona fasciculata type, but form zona glomerulosa cells. It is thought that cell migration occurs from the cells of the outer region of the zona fasciculata to the zona reticularis and that this is, normally, a slow process.

scholarly journals Transcriptome Analysis Reveals Differentially Expressed Transcripts in Rat Adrenal Zona Glomerulosa and Zona Fasciculata

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1755-1763 ◽  
Author(s):  
Koshiro Nishimoto ◽  
Christine S. Rigsby ◽  
Tao Wang ◽  
Kuniaki Mukai ◽  
Celso E. Gomez-Sanchez ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Zona Glomerulosa ◽  
Male Rats ◽  
Zona Fasciculata ◽  
Rt Pcr ◽  
Cellular Mechanisms ◽  
Hormone Production ◽  
Invaluable Tool ◽  
Laser Capture ◽  
Microarray Chips

In mammals, aldosterone is produced in the zona glomerulosa (zG), the outermost layer of the adrenal cortex, whereas glucocorticoids are produced in adjacent zona fasciculata (zF). However, the cellular mechanisms controlling the zonal development and the differential hormone production (i.e. functional zonation) are poorly understood. To explore the mechanisms, we defined zone-specific transcripts in this study. Eleven-week-old male rats were used and adrenal tissues were collected from zG and zF using laser-capture microdissection. RNA was isolated, biotin labeled, amplified, and hybridized to Illumina microarray chips. The microarray data were compared by fold change calculations. In zG, 235 transcripts showed more than a 2-fold up-regulation compared to zF with statistical significance. Similarly, 231 transcripts showed up-regulation in zF. The microarray findings were validated using quantitative RT-PCR and immunohistochemical staining on selected transcripts, including Cyp11b2 (zG/zF: 214.2x), Rgs4 (68.4x), Smoc2 (49.3x), and Mia1 (43.1x) in zG as well as Ddah1 (zF/zG 16.2x), Cidea (15.5x), Frzb (9.5x), and Hsd11b2 (8.3x) in zF. The lists of transcripts obtained in the current study will be an invaluable tool for the elucidation of cellular mechanisms leading to zG and zF functional zonation.

scholarly journals Vitamin D Regulatory Effect on Restraint Stress-Induced Changes on Serum Corticosterone and Hippocampus BDNF Levels in Male Rats

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Katayoun Sedaghat ◽  
Sara Choobdar ◽  
Ahmad Reza Bandegi ◽  
Zahra Ghods
Keyword(s):  
Vitamin D ◽  
Chronic Stress ◽  
Restraint Stress ◽  
Male Rats ◽  
Negative Effects ◽  
Bdnf Level ◽  
Serum Corticosterone ◽  
Protein Levels ◽  
Induced Changes ◽  
The Impact

Background: Chronic stress exerts negative effects on cognitive functions through inducing changes in the hippocampus. Brain-derived neurotrophic factor (BDNF) is an essential factor in cognitive activities, which is considerably reduced under chronic stress. 1,25(OH)2 vitamin D plays neuroprotective roles partially by regulating the expression of various neurotrophic factors. Objectives: Since few studies have studied the impact of vitamin D on BDNF level, we conducted this brief experiment to understand the role of vitamin D in maintaining hippocampal BDNF protein levels by using restraint as a model of chronic stress in rats. Methods: Rats underwent restraint stress 3 h/day for 28 days, during which they received vitamin D (5, 10 μg/kg) or its vehicle (IP, twice weekly). After the stress period, serum corticosterone (CORT) and hippocampus BDNF protein levels were measured. Results: Restraint stress increased serum CORT (P < 0.001) and reduced BDNF protein levels (P < 0.001) as compared to the non-stress group. Vitamin D markedly maintained BDNF level close to normal (P < 0.001), but did not change CORT level significantly. Conclusions: This study demonstrated that 3h/day of chronic restraint stress for 28 days boosted serum CORT and declined hippocampal BDNF levels, similar to stronger restraint stress models. Vitamin D maintained BDNF level close to normal in the hippocampus, but it did not affect CORT level significantly.

scholarly journals GH-receptor distribution in the ovine foetal adrenal gland: ontogenic and functional studies

1999 ◽  
Vol 162 (2) ◽  
pp. 197-205 ◽  
Author(s):  
AC McFarlane ◽  
SR Edmondson ◽  
EM Wintour ◽  
GA Werther
Keyword(s):  
Adrenal Gland ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Functional Studies ◽  
Receptor Mrna ◽  
Gh Receptor ◽  
Basal Plasma ◽  
Size And Morphology ◽  
And Function

In order to examine the role of GH in the regulation of foetal adrenal development and function, we have localized GH-receptor mRNA and protein in adrenal glands of ovine foetuses at specific stages of gestation. Adrenals from 60-75 day (n=4), 100-110 day (n=4) and 140-145 day (n=3) foetal sheep (term is 145-150 days) and non-pregnant adult animals (n=3) were dissected and fixed. GH-receptor mRNA localization was studied by in situ hybridization using a (35)S-labelled antisense cRNA probe, and protein by immunohistochemistry using a specific monoclonal antibody to the GH-receptor. At all ages studied, GH-receptor mRNA and immunoreactivity could be detected throughout the adrenocortical region. In adult adrenals, GH-receptor mRNA and immunoreactivity were also evident throughout the adrenocortical zone, with the strongest expression confined to a defined region of cells at the interface between the zona glomerulosa and zona fasciculata. Northern blot analysis of 100 day and 140 day foetal adrenals confirmed the presence of a 4.4 kb GH-receptor mRNA transcript, while immunoblotting of foetal adrenals at approximately 110 days of gestation revealed a 55 kDa GH-receptor species. To study the effect of GH on the function and growth of the immature foetal adrenal gland in vivo, chronically catheterized ovine foetuses (n=4), between 100 and 110 days of gestation, were given a pulsatile infusion of recombinant bovine GH (125 microgram/15 min, 24 pulses/24 h) for 72 h. Plasma cortisol and aldosterone levels were compared with age-matched controls receiving saline infusion alone (n=4). It was found that there was no difference in the basal plasma level of cortisol or aldosterone, and that infusion of GH did not alter steroid levels or gross adrenal size and morphology. These studies demonstrate strong expression of the GH-receptor in the developing ovine foetal adrenal cortex. However, in the immature foetus GH infusion is without effect on plasma steroid levels, suggesting that the steroidogenic action of GH in the ovine foetus may be gestationally dependent.

scholarly journals DIAGNOSIS OF ENDOCRINE DISEASE: 18-Oxocortisol and 18-hydroxycortisol: is there clinical utility of these steroids?

2018 ◽  
Vol 178 (1) ◽  
pp. R1-R9 ◽  
Author(s):  
Jacques W M Lenders ◽  
Tracy Ann Williams ◽  
Martin Reincke ◽  
Celso E Gomez-Sanchez
Keyword(s):  
Primary Aldosteronism ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Endocrine Disease ◽  
Familial Hyperaldosteronism ◽  
High Concentrations ◽  
And Function ◽  
Type 3

Since the early 1980s 18-hydroxycortisol and 18-oxocortisol have attracted attention when it was shown that the urinary excretion of these hybrid steroids was increased in primary aldosteronism. The development and more widespread use of specific assays has improved the understanding of their role in the (patho)physiology of adrenal disorders. The adrenal site of synthesis is not fully understood although it is clear that for the synthesis of 18-hydroxycortisol and 18-oxocortisol the action of both aldosterone synthase (zona glomerulosa) and 17α-hydroxylase (zona fasciculata) is required with cortisol as main substrate. The major physiological regulator is ACTH and the biological activity of both steroids is very low and therefore only very high concentrations might be effectivein vivo. In healthy subjects, the secretion of both steroids is low with 18-hydroxycortisol being substantially higher than that of 18-oxocortisol. The highest secretion of both steroids has been found in familial hyperaldosteronism type 1 (glucocorticoid-remediable aldosteronism) and in familial hyperaldosteronism type 3. Lower but yet substantially increased secretion is found in patients with aldosterone-producing adenomas in contrast to bilateral hyperplasia in whom the levels are similar to patients with hypertension. Several studies have attempted to show that these steroids, in particular, peripheral venous plasma 18-oxocortisol, might be a useful discriminatory biomarker for subtyping PA patients. The current available limited evidence precludes the use of these steroids for subtyping. We review the biosynthesis, regulation and function of 18-hydroxycortisol and 18-oxocortisol and their potential utility for the diagnosis and differential diagnosis of patients with primary aldosteronism.

scholarly journals Developmental programming of adult adrenal structure and steroidogenesis: effects of fetal glucocorticoid excess and postnatal dietary omega-3 fatty acids

2010 ◽  
Vol 205 (2) ◽  
pp. 171-178 ◽  
Author(s):  
Brendan J Waddell ◽  
Maike Bollen ◽  
Caitlin S Wyrwoll ◽  
Trevor A Mori ◽  
Peter J Mark
Keyword(s):  
Fatty Acids ◽  
Dietary Intervention ◽  
Zona Glomerulosa ◽  
Interactive Effects ◽  
Adrenocortical Function ◽  
Zona Fasciculata ◽  
Omega 3 ◽  
Pregnant Rats ◽  
Dexamethasone Acetate ◽  
And Function

Fetal glucocorticoid excess programs a range of detrimental outcomes in the adult phenotype, at least some of which may be due to altered adult adrenocortical function. In this study, we determined the effects of maternal dexamethasone treatment on offspring adrenal morphology and function, as well as the interactive effects of postnatal dietary omega-3 (n-3) fatty acids. This postnatal dietary intervention has been shown to alleviate many of the programming outcomes in this model, but whether this is via the effects on adrenal function is unknown. Dexamethasone acetate was administered to pregnant rats (0.75 μg/ml drinking water) from day 13 to term. Cross-fostered offspring were raised on either a standard or high-n-3 diet. Adrenal weight (relative to body weight) at 6 months of age was unaffected by prenatal dexamethasone, regardless of postnatal diet, and stereological analysis showed no effect of dexamethasone on the volumes of adrenal components (zona glomerulosa, zona fasciculata/reticularis or adrenal medulla). Expression of key steroidogenic genes (Cyp11a1 and Star) was unaffected by either prenatal dexamethasone or postnatal diet. In contrast, adrenal expression of Mc2r mRNA, which encodes the ACTH receptor, was higher in offspring of dexamethasone-treated mothers, an effect partially attenuated by the Hn3 diet. Moreover, stress-induced levels of plasma and urinary corticosterone and urinary aldosterone were elevated in offspring of dexamethasone-treated mothers, indicative of enhanced adrenal responsiveness. In conclusion, this study shows that prenatal exposure to dexamethasone does not increase basal adrenocortical activity but does result in a more stress-responsive adrenal phenotype, possibly via increased Mc2r expression.

Paliperidone attenuates chronic stress-induced changes in the expression of inflammasomes-related protein in the frontal cortex of male rats

2021 ◽  
Vol 90 ◽  
pp. 107217
Author(s):  
Karina S. MacDowell ◽  
David Martín-Hernández ◽  
Cristina Ulecia-Morón ◽  
Álvaro G. Bris ◽  
José L.M. Madrigal ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Chronic Stress ◽  
Male Rats ◽  
Related Protein ◽  
Induced Changes

Effect of adrenocorticotrophin on cortisol and androstenedione secretion from dispersed cells of guinea-pig adrenal zonae fasciculata and reticularis

1986 ◽  
Vol 109 (3) ◽  
pp. 399-404 ◽  
Author(s):  
W. R. Robertson ◽  
B. Davison ◽  
D. C. Anderson ◽  
J. Frost ◽  
A. Lambert
Keyword(s):  
Body Weight ◽  
Guinea Pig ◽  
Adrenal Cortex ◽  
Zona Glomerulosa ◽  
Adrenal Weight ◽  
Zona Fasciculata ◽  
Cortisol Secretion ◽  
Acth Stimulation ◽  
17 Hydroxyprogesterone ◽  
Dispersed Cells

ABSTRACT We have studied cortisol and androstenedione secretion by dispersed cells of the outer zona fasciculata (ZF) plus zona glomerulosa, and the inner zona reticularis (ZR) plus medulla of the guinea-pig adrenal. The ZF and ZR were microdissected apart, the cells dispersed and incubated (200 000 cells/ml) for 90 min in the presence of adrenocorticotrophin (ACTH; 500 ng/l), dibutyryl cyclic AMP (dbcAMP; 1 mmol/l), pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol and 21-deoxycortisol. The steroid concentrations were 5–25 μmol/l. Cortisol secretion was assayed by radioimmunoassay. There was no detectable cortisol secretion ( < 50 nmol/l) from the ZR in the controls (no additive) or after dbcAMP stimulation. Adrenocorticotrophin-stimulated cortisol secretion was also low (range < 50–340 nmol/l). In contrast the ZF secreted 177–379 (control), 828–2052 (dbcAMP) and 2863–9735 (ACTH) nmol cortisol/l. There was no detectable (i.e. < 2 nmol/l) cAMP production by ZR or ZF either basally (no ACTH) or after ACTH stimulation (500 ng/l). Challenge of the ZR cells with each cortisol precursor steroid (5 μmol/l) increased (P < 0·05) cortisol secretion over that seen with the corresponding basal and ACTH-stimulated controls. Thus pregnenolone, 17-hydroxypregnenolone, 17-hydroxyprogesterone, 11-deoxycortisol and 21-deoxycortisol (converted directly to cortisol by 21-hydroxylase) gave rise to (mean ± s.d., n = 4) 406 ± 86, 680 ± 180, 1307 ± 111, 1141 ± 234 and 3160 ± 419 nmol cortisol/l respectively. The corresponding figures for the ZF prepared from the same adrenal cortex were 3919 ± 309, 4122 ± 97, 5766 ± 615, 5035 ± 260 and 6954 ± 755 nmol cortisol/l. With pregnenolone (25 μmol/l), cortisol secretion increased to 7847 ± 1424 (ZR) and 12880 ± 982 nmol/l (ZF), a ZR:ZF ratio of 0·6 compared with 0·1 for pregnenolone at 5 μmol/l. Androstenedione was secreted in the basal state by both ZF and ZR in similar quantities, i.e. 3·7 ± 0·3 and 3·7 ± 0·4 nmol/l (n = 9 and 14 respectively). Both cell types were ACTH sensitive, with androstenedione secretion increasing to 28 ± 4·8 (ZF) and 12·5 ± 0·9 (ZR) nmol/l. There was a direct correlation (r = 0·924, P < 0·05) between total adrenal weight and body weight, between the percentage ZR in the cortex and adrenal weight (r = 0·96, P < 0·05) and between the percentage ZR and body weight (r = 0·981, P< 0·05). In a mature animal (800–1000 g) the ZR may occupy > 66% of the adrenal cortex. The mean diameters of cells from the ZF and ZR were 21 and 25 μm respectively. J. Endocr. (1986) 109, 399–404

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