IN VITRO MODIFICATION OF RAT ADRENAL ZONA FASCICULATA/RETICULARIS FUNCTION BY THE ZONA GLOMERULOSA

1976 ◽  
Vol 81 (2) ◽  
pp. 340-350 ◽  
Author(s):  
G. P. Vinson ◽  
Barbara J. Whitehouse
Keyword(s):  
Adrenal Cortex ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Equivalent Amount ◽  
Adrenal Tissue ◽  
Specific Analysis ◽  
Adrenal Zona Fasciculata ◽  
Preincubation Medium

ABSTRACT Following earlier findings, the possibility that the zona glomerulosa of the rat adrenal cortex may modify inner zone function was investigated. In a series of in vitro experiments designed to test this hypothesis it was found that: 1. Inner zone preparations gave significantly more steroid than either glomerulosa tissue incubated alone, or (for the first 40 min of a two hour incubation), an equivalent amount of whole adrenal tissue. Whole tissue yields were greater than glomerulosa alone only at the 120 min point. At no time did the whole tissue output approach the total anticipated by addition of separate inner zone and glomerulosa yields. 2. In 20 min incubations, inner zone steroid output generally could be depressed by the addition of a glomerulosa preincubation medium (PIM), or a steroid extract of a glomerulosa PIM, or by the addition of 100 ng aldosterone. Inner zone PIM had less effect. 3. Higher concentrations of aldosterone gave increased inhibition of inner zone corticosteroid production. The results indicated that only a part of the total corticosterone output was aldosterone sensitive in this way. 4. More specific analysis of the steroids showed that yields of corticosterone from endogenous precursors were depressed by aldosterone, but deoxycorticosterone and 18-hydroxydeoxycorticosterone were not. In the same incubations the presence of aldosterone had no effect on the formation of these three products from [3H]pregnenolone. In total the results suggest that the presence of the glomerulosa may affect inner zone function by inhibiting the secretion of corticosterone formed from endogenous precursors. It is possible that aldosterone is the agent of this effect.

IN VITRO RESPONSES OF FOCAL HYPERPLASTIC TISSUE OF THE HUMAN ADRENAL ZONA FASCICULATA TO ACTH

1977 ◽  
Vol 86 (2) ◽  
pp. 363-368 ◽  
Author(s):  
Kenneth V. Honn ◽  
Walter Chavin ◽  
Amnuay Singhakowinta
Keyword(s):  
Adrenocortical Function ◽  
Zona Fasciculata ◽  
Adrenal Tissue ◽  
Basal Cortisol ◽  
Aldosterone Production ◽  
Hyperplastic Tissue ◽  
Normal Human ◽  
Adrenal Zona Fasciculata ◽  
Normal Adrenal Tissue

ABSTRACT The temporal cAMP, cortisol and aldosterone responses to ACTH of focal hyperplasia of the zona fasciculata and of normal human adrenocortical tissue were investigated. ACTH significantly increased cAMP levels (1 min) and cortisol output (2 min) in normal adrenal tissue but not in hyperplastic tissue. However, following ACTH treatment cortisol and aldosterone production were depressed in the abnormal adrenal tissue below the untreated or the ACTH stimulated normal adrenal tissue. In addition, basal cortisol and aldosterone production of the hyperplastic adrenal tissue was elevated above that of the normal adrenal tissue. These findings suggest that the cAMP second messenger concept may be only one of several mechanisms in the modulation of human adrenocortical function.

In vitro conversion of cholesterol into aldosterone and cortisol in different zones of the bovine adrenal cortex

1982 ◽  
Vol 101 (3) ◽  
pp. 436-441 ◽  
Author(s):  
Karl-Eric Karlmar
Keyword(s):  
Adrenal Cortex ◽  
Total Content ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Oxidoreductase Activity ◽  
Chain Cleavage ◽  
Specific Fraction ◽  
The Individual ◽  
Cytochrome P 450

Abstract. The individual steps in the formation of aldosterone and cortisol from cholesterol were assayed in different subcellular preparations from the inner and outer zones of bovine adrenal cortex. In zona glomerulosa the 11β-, 18- and 21-hydroxylase activities were relatively high, whereas the 17α-hydroxylase activity was relatively low. Cholesterol side-chain cleavage and 3β-hydroxysteroid-Δ5-oxidoreductase activity were similar in zona glomerulosa and zona fasciculata-reticularis. The differences were however only quantitative. In no case one specific fraction was totally devoid of enzyme activity. The total content of mitochondrial cytochrome P-450 was relatively high in zona fasciculata-reticularis whereas the content of microsomal cytochrome P-450 was similar in the two fractions. In view of the relatively small differences observed, it seems likely that other factors than distribution of the above enzymes are of major importance for the specific production of gluco- and mineralocorticoids in the two layers.

VERGLEICHENDE UNTERSUCHUNGEN ZUR BIOGENESE VON STEROIDHORMONEN BEI DURCHSTRÖMUNG ÜBERLEBENDER NEBENNIEREN EINER PATIENTIN MIT CUSHING- UND EINER PATIENTIN MIT CONN-SYNDROM

1963 ◽  
Vol 43 (3) ◽  
pp. 419-429 ◽  
Author(s):  
H. Schriefers ◽  
J. M. Bayer ◽  
M. Pittel
Keyword(s):  
Adrenal Gland ◽  
Adrenal Cortex ◽  
Zona Glomerulosa ◽  
Secretion Rate ◽  
Zona Fasciculata ◽  
Conn’S Syndrome ◽  
Adrenal Cortical Adenoma ◽  
Aldosterone Production ◽  
The Right

ABSTRACT In vitro perfusion experiments were carried out with adrenal glands surgically removed from a patient with Cushing's syndrome (hyperplasia of the adrenal cortex) and a patient with Conn's syndrome (adrenal cortical adenoma). From the perfusates the following steroids were extracted, estimated and identified: cortisol, corticosterone, 11β-hydroxyandrostenedione, cortisone and aldosterone. The secretion capacities of the right Cushing adrenal and of the adrenal gland bearing the adenoma were compared with each other. In both adrenals cortisol was the main secretion product and the secretion rates of aldosterone were lowest and practically equal. The Cushing adrenal differed from the adrenal gland with the adenoma in its higher secretion rate of all investigated steroids except aldosterone, in its higher cortisol/aldosterone ratio and in its response to the administration of ACTH. To this stimulus the aldosterone production of the Cushing adrenal reacted in the same rate as the cortisol release. The adrenal gland with the adenoma of the patient with Conn's syndrome had only a relatively higher aldosterone secretion rate in respect to its lower cortisol production (lower cortisol/aldosterone ratio). The total preparation consisting of the adrenal with the adenoma responded neither to ACTH nor to hypertensin. The missing response of the adrenal cortex not including the tumor to ACTH is explained by the structural change in the sense of the so called regressive transformation (small zona fasciculata with relative large zona glomerulosa and reticularis) which was found in our case. Dehydroepiandrosterone was demonstrable in none of the perfusate extracts even under the condition where the left adrenal of the Cushing patient was perfused with added 17α-hydroxy-pregnenolone.

PARALLEL BIOCHEMICAL AND HISTOCHEMICAL STUDIES OF AN ADRENOCORTICAL ADENOMA FROM A PATIENT WITH PRIMARY ALDOSTERONISM

1961 ◽  
Vol 38 (2) ◽  
pp. 207-219 ◽  
Author(s):  
Jean Davignon ◽  
Gilles Tremblay ◽  
Wojciech Nowaczynski ◽  
Erich Koiw ◽  
Jacques Genest
Keyword(s):  
Primary Aldosteronism ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Morphological Aspect ◽  
Adrenocortical Adenoma ◽  
Acth Stimulation ◽  
Chromatographic Techniques ◽  
Striking Increase ◽  
Adrenal Tissue

ABSTRACT An adrenocortical adenoma surgically removed from a patient with primary aldosteronism was investigated by histological, histochemical and incubation-chromatographic techniques and compared to intact adrenal tissue excised from the contralateral gland. The tumour was composed almost entirely of fasciculata-like tissue and released »in vitro« cortisol, corticosterone, aldosterone, cortisone and 17-hydroxy-11-deoxycorticosterone but no measurable amounts of 11β-hydroxy-androstenedione. In contrast to the contralateral gland with prominent zona glomerulosa and atrophic zona fasciculata, which responded poorly to corticotrophin (ACTH) stimulation, the tumour responded by a striking increase in the formation of cortisol, corticosterone and aldosterone. An attempt was made to correlate the morphological aspect with the biochemical findings »in vitro«.

THE ROLE OF PROGESTERONE IN THE BIOSYNTHESIS OF CORTISOL IN HUMAN ADRENAL TISSUE

1968 ◽  
Vol 41 (3) ◽  
pp. 319-326 ◽  
Author(s):  
E. H. D. CAMERON ◽  
M. A. BEYNON ◽  
K. GRIFFITHS
Keyword(s):  
Adrenal Cortex ◽  
Biosynthetic Pathway ◽  
Zona Fasciculata ◽  
Relative Importance ◽  
Mathematical Approach ◽  
Zona Reticularis ◽  
Adrenal Tissue

SUMMARY The ability of cells from the zona fasciculata and the zona reticularis of the human adrenal cortex to transform labelled pregnenolone and progesterone to cortisol in vitro was investigated. Examination of the 3H:14C ratios of 16α-hydroxyprogesterone, 17α-hydroxyprogesterone, 11-deoxycorticosterone and cortisol formed during incubations in vitro suggested that the role of progesterone in the transformation of pregnenolone to cortisol might be a relatively minor one. An attempt was subsequently made to estimate the relative importance of the biosynthetic pathway to cortisol by way of progesterone in hyperplastic adrenal tissue by a mathematical approach.

scholarly journals Human Adrenocortical Remodeling Leading to Aldosterone-Producing Cell Cluster Generation

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Koshiro Nishimoto ◽  
Tsugio Seki ◽  
Yuichiro Hayashi ◽  
Shuji Mikami ◽  
Ghaith Al-Eyd ◽  
...  
Keyword(s):  
Adrenal Cortex ◽  
Zona Glomerulosa ◽  
Statistical Analyses ◽  
Cell Cluster ◽  
Zona Fasciculata ◽  
Undifferentiated Cell ◽  
Immunohistochemical Detection ◽  
Cluster Generation ◽  
Over Time ◽  
Cell Zone

Background. The immunohistochemical detection of aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1) has enabled the identification of aldosterone-producing cell clusters (APCCs) in the subcapsular portion of the human adult adrenal cortex. We hypothesized that adrenals have layered zonation in early postnatal stages and are remodeled to possess APCCs over time.Purposes. To investigate changes in human adrenocortical zonation with age.Methods. We retrospectively analyzed adrenal tissues prepared from 33 autopsied patients aged between 0 and 50 years. They were immunostained for CYP11B2 and CYP11B1. The percentage of APCC areas over the whole adrenal area (AA/WAA, %) and the number of APCCs (NOA, APCCs/mm2) were calculated by four examiners. Average values were used in statistical analyses.Results. Adrenals under 11 years old had layered zona glomerulosa (ZG) and zona fasciculata (ZF) without apparent APCCs. Some adrenals had an unstained (CYP11B2/CYP11B1-negative) layer between ZG and ZF, resembling the rat undifferentiated cell zone. Average AA/WAA and NOA correlated with age, suggesting that APCC development is associated with aging. Possible APCC-to-APA transitional lesions were incidentally identified in two adult adrenals.Conclusions. The adrenal cortex with layered zonation remodels to possess APCCs over time. APCC generation may be associated with hypertension in adults.

scholarly journals Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland

2011 ◽  
Vol 46 (3) ◽  
pp. 227-232 ◽  
Author(s):  
Rebecca J Gorrigan ◽  
Leonardo Guasti ◽  
Peter King ◽  
Adrian J Clark ◽  
Li F Chan
Keyword(s):  
Adrenal Gland ◽  
Adrenal Cortex ◽  
Accessory Protein ◽  
Zona Fasciculata ◽  
Accessory Proteins ◽  
Similar Function ◽  
Glucocorticoid Deficiency ◽  
Inactivating Mutations

The melanocortin-2-receptor (MC2R)/MC2R accessory protein (MRAP) complex is critical to the production of glucocorticoids from the adrenal cortex. Inactivating mutations in either MC2R or MRAP result in the clinical condition familial glucocorticoid deficiency. The localisation of MC2R together with MRAP within the adrenal gland has not previously been reported. Furthermore, MRAP2, a paralogue of MRAP, has been shown in vitro to have a similar function to MRAP, facilitating MC2R trafficking and responsiveness to ACTH. Despite similar MC2R accessory functions, in vivo, patients with inactivating mutations of MRAP fail to be rescued by a functioning MRAP2 gene, suggesting differences in adrenal expression, localisation and/or function between the two MRAPs. In this study on the rat adrenal gland, we demonstrate that while MRAP and MC2R are highly expressed in the zona fasciculata, MRAP2 is expressed throughout the adrenal cortex in low quantities. In the developing adrenal gland, both MRAP and MRAP2 are equally well expressed. The MC2R/MRAP2 complex requires much higher concentrations of ACTH to activate compared with the MC2R/MRAP complex. Interestingly, expression of MC2R and MRAP in the undifferentiated zone would support the notion that ACTH may play an important role in adrenal cell differentiation and maintenance.

Electrical responses in cat adrenal cortex: possible relation to aldosterone secretion.

1979 ◽  
Vol 237 (2) ◽  
pp. E158 ◽  
Author(s):  
E Natke ◽  
E Kabela
Keyword(s):  
Membrane Potential ◽  
Angiotensin Ii ◽  
Adrenal Cortex ◽  
Adrenal Glands ◽  
Membrane Depolarization ◽  
Zona Glomerulosa ◽  
Membrane Potentials ◽  
Zona Fasciculata ◽  
Aldosterone Secretion ◽  
Stimulus Secretion Coupling

The effects of secretagogues for aldosterone release were studied on the membrane potential of cells in the adrenal cortex of the cat. Adrenal glands were excised, sliced, and continuously superfused. Membrane potentials were recorded from both zona glomerulosa and zona fasciculata-reticularis. Secretagogues, angiotensin II (1 microgram/ml) and 20 mM KCl, were found to depolarize cells rapidly. Ouabain (10(-5) M) also depolarized the membrane potential although the response was sluggish. Samples of the superfusate were collected and analyzed by radioimmunoassay for their aldosterone and cortisol content. Depolarizing concentrations of angiotensin II, KCl, and ouabain seemed to increase aldosterone release. Cortisol output was more variable. Saralasin blocked the effects of angiotensin II on the membrane potential. These experiments suggest that membrane depolarization plays a role in the stimulus-secretion coupling of mineral corticoids.

scholarly journals Oxygen-dependence of ACTH-stimulated aldosterone and corticosterone synthesis in the rat adrenal cortex: developmental aspects

2002 ◽  
Vol 172 (3) ◽  
pp. 595-604 ◽  
Author(s):  
ED Bruder ◽  
AK Nagler ◽  
H Raff
Keyword(s):  
Enzyme Activity ◽  
Age Groups ◽  
Maximal Activity ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Steroid Synthesis ◽  
Camp Generation ◽  
Aldosterone Production ◽  
Health And Disease

The control of ACTH-stimulated steroidogenesis under decreasing levels of O(2) is not fully understood. The purpose of this study was to examine the effects of decreased O(2) in vitro on rat adrenocortical steroid synthesis at different stages of development. Of interest was the evaluation of the effect of low O(2) on steroidogenesis during the stress hyporesponsive period of the neonate. Rats were killed at 7, 14, or 42 days of age, adrenals collected and capsules (zona glomerulosa, ZG) separated from subcapsules (zona fasciculata/reticularis, ZFR). Cells were dispersed and placed into glass vials each gassed with a different level of O(2) (21, 5, 2, 1, or 0% O(2)). The entire steroidogenic pathway was analyzed by measuring ACTH-stimulated cAMP, corticosterone and aldosterone production during a 2 h incubation. In addition, the early (P450 scc) and late (P450c11 beta and P450 aldo) pathway activities were examined in the presence of cyanoketone. The PO(2) for half-maximal activity (P(50)) for aldosterone synthesis in ZG cells from 7- and 42-day-old rats was approximately 28 mmHg and 7 mmHg respectively, indicating that cells from older rats were more resistant to inhibition by low O(2). The P(50) for cAMP production from the ZG was approximately 14 mmHg for both age groups. The P(50) for corticosterone synthesis was approximately 28 mmHg and <7 mmHg in ZFR cells from 7- and 42-day-old cells respectively. The only enzyme activities affected by low O(2) (<35 mmHg) were P450 aldo and P450 scc. Moderate decreases in O(2) (from approximately 150 mmHg) decreased aldosteronogenesis, possibly due to observed decreases in cAMP generation, but not due to decreases in steroidogenic enzyme activity (7-day-old). Severe decreases in O(2) presumably inhibited P450 aldo through a direct effect on enzyme activity (both ages). P450 scc activity (including cholesterol transport) also seems to be decreased by very low O(2) (7-day-old). These findings illustrate a novel developmental alteration in O(2)-regulated steroid production, and may have implications for neonatal health and disease.

scholarly journals Human Adrenal Cortical Zone Changes With Aging

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A69-A69
Author(s):  
Yuta Tezuka ◽  
Nanako Atsumi ◽  
Amy Blinder ◽  
Juilee Rege ◽  
Thomas J Giordano ◽  
...  
Keyword(s):  
Adrenal Cortex ◽  
Adult Life ◽  
Rank Correlation ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Strong Positive Correlation ◽  
Adult Life Span ◽  
Functional Changes ◽  
Morphological Studies ◽  
Age Related

Abstract Background: Previous adrenal morphological studies have shown that the zona reticularis (ZR) and the zona glomerulosa (ZG) decrease in size with aging. Although several lines of evidence indicate that the hypothalamic-pituitary-adrenal axis becomes hyperactive in elderly, little is known about age-related transformations of the adrenal zona fasciculata (ZF). Objectives: To investigate the morphological and functional changes of the adrenal cortex across the adult life span, with emphasis on: 1) the understudied ZF, and 2) potential sexual dimorphisms. Methods: We used immunohistochemistry to evaluate the expression of several cortical proteins: aldosterone synthase (CYP11B2), visinin-like protein 1 (VSNL1), 3β-hydroxysteroid dehydrogenase type II (HSD3B2), 11β-hydroxylase (CYP11B1) and cytochrome b5 type A (CYB5A). The ZF area was estimated by subtracting the VSNL1-positive (a ZG marker) area from the HSD3B2-expressing area (ZG and ZF). All captured images were quantitated by ImageJ. In addition, we employed liquid chromatography-tandem mass spectrometry to quantify the morning serum concentrations of 6 steroids: cortisol, 11-deoxycortisol (11dF), 17α-hydroxyprogesterone (17OHP4), 11-deoxycorticosterone (DOC), corticosterone, and androstenedione (A4). The Mann-Whitney U test and Spearman’s rank correlation coefficients were used for statistical analysis, as appropriate. Results: We included 60 adrenal glands from 30 men and 30 women, with ages between 18–86 years. The total cortical area was positively correlated with age (r=0.34, p=0.008), and this association was significant only in men (p=0.02). Both the total (VSNL1-positive) and functional ZG (CYP11B2-positive) areas declined abruptly with aging in men (r=-0.57 and -0.76, p=0.001 and p&lt;0.0001, respectively), but not women (p=0.06 and 0.27, respectively). The CYB5A-positive area, marking the ZR, correlated negatively with age (r=-0.76, p&lt;0.0001) in both sexes. In contrast, the estimated ZF area showed a strong positive correlation with age both in men (r=0.59, p=0.0006) and women (r=0.49, p=0.007), while CYP11B1-positive area remained stable across ages (p=0.86). Finally, we measured morning levels of 6 steroids in 149 men and 149 women, with ages between 21–95 years, matched for age and body mass index. Serum cortisol, corticosterone, and DOC levels remained relatively stable across ages (p=0.38, 0.64 and 0.25, respectively), while 11dF levels increased slightly with age (r=0.16 and p=0.007), particularly so in men (p=0.005). Expectedly, 17OHP4 and A4 declined with aging (r=-0.37 and -0.37, p&lt;0.0001 for both). Conclusions: In contrast with the ZG and ZR, the ZF and the total adrenal cortex area enlarge with aging. An abrupt decline of the ZG occurs with age in men, but not in women, possibly contributing to sexual dimorphism in cardiovascular risk.

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