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.

BIOCHEMISTRY OF HISTOLOGICALLY DEFINED ZONES IN THE ADRENAL CORTEX: CORTISOL SYNTHESIS IN THE HORSE

1967 ◽  
Vol 37 (4) ◽  
pp. 413-NP ◽  
Author(s):  
E. H. D. CAMERON ◽  
J. K. GRANT
Keyword(s):  
Adrenal Cortex ◽  
Zona Fasciculata ◽  
Subsequent Formation ◽  
Zona Reticularis ◽  
Cell Form ◽  
Reticular Cells ◽  
Rate Limiting

SUMMARY The ability of cells from the zona fasciculata and zona reticularis of the horse adrenal cortex to transform [7α-3H]pregnenolone, [4-14C]progesterone, [7α-3H]17α-hydroxypregnenolone and [4-14C]17α-hydroxyprogesterone to cortisol in vitro was investigated. It was found that: (1) Both types of cell form cortisol from these steroids. (2) The transformation is greater in fascicular cells. (3) The formation of 17α-hydroxyprogesterone from pregnenolone (via either progesterone or 17α-hydroxypregnenolone) is slower that the subsequent formation of cortisol from 17α-hydroxyprogesterone. (4) The formation of 17α-hydroxyprogesterone from 17α-hydroxypregnenolone is rate-limiting in cortisol formation, but is about 2·4 times faster in fascicular than in reticular cells. (5) 17α-Hydroxylation of progesterone is also faster in fascicular than in reticular cells.

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.

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.

PROPERTIES OF RAT ADRENAL ZONA RETICULARIS CELLS: PRODUCTION AND STIMULATION OF CERTAIN STEROIDS

1979 ◽  
Vol 83 (3) ◽  
pp. 435-447 ◽  
Author(s):  
J. B. G. BELL ◽  
R. P. GOULD ◽  
P. J. HYATT ◽  
J. F. TAIT ◽  
S. A. S. TAIT
Keyword(s):  
Adrenal Cortex ◽  
Significant Role ◽  
Zona Fasciculata ◽  
Cell Type ◽  
Acth Stimulation ◽  
Specific Stimulus ◽  
Zona Reticularis ◽  
Cell Pool ◽  
Stimulation Of

The outputs of corticosterone, deoxycorticosterone and androstenedione from dispersed, purified rat adrenal zona reticularis and zona fasciculata cells have been measured by radioimmunoassay. Preferential production of deoxycorticosterone by zona reticularis cells was demonstrated by their higher basal deoxycorticosterone: corticosterone ratio when compared with zona fasciculata cells. Adrenocorticotrophin (ACTH) stimulated corticosterone output by all cell pools prepared by unit gravity (1 g) sedimentation, zona fasciculata cells being stimulated 130-fold compared with 20-fold for the zona reticularis cells in relation to their basal corticosterone output. In every cell pool, ACTH stimulated the output of corticosterone more than it stimulated the output of deoxycorticosterone. In parallel cell preparations, it was shown that ACTH increased the conversion of tracer amounts of radioactive deoxycorticosterone to corticosterone and decreased the conversion of radioactive corticosterone to 11-dehydrocorticosterone. Adrenocorticotrophin did not increase the conversion of radioactive deoxycorticosterone to total 11-oxygenated steroids (corticosterone+ 11-dehydrocorticosterone). It is unlikely therefore that ACTH stimulates 11 β-hydroxylation. Data indicate that the ratio of deoxycorticosterone to total 11-oxygenated steroids (corticosterone +11-dehydrocorticosterone) is characteristic for each cell type, and that this ratio will be relatively independent of ACTH stimulation or the amount of pregnenolone substrate available. Basal androstenedione outputs were similar for both types of cell, and ACTH stimulation was very small, being slightly greater for zona fasciculata than for zona reticularis cells. The contribution of the zona reticularis cells to the basal output of any steroid by the cells of the inner two zones of the adrenal cortex of the rat was relatively small (20% for deoxycorticosterone and 10% for corticosterone) and was even less after stimulation by ACTH. Unless a specific stimulus can be found, therefore, a significant role for the zona reticularis cannot yet be established.

scholarly journals IDENTIFICATION OF PEROXISOMES IN THE RAT ADRENAL CORTEX

1972 ◽  
Vol 20 (3) ◽  
pp. 173-179 ◽  
Author(s):  
MARGARET E. BEARD
Keyword(s):  
Acid Phosphatase ◽  
Adrenal Cortex ◽  
Zona Fasciculata ◽  
Positive Staining ◽  
Staining Reaction ◽  
Dense Matrix ◽  
Zona Reticularis ◽  
Liver And Kidney ◽  
Branched Structures ◽  
Electron Dense Matrix

Organelles with the ultrastructure and cytochemical characteristics of peroxisomes (microbodies) have been identified in cells of the zona fasciculata and zona reticularis of the rat adrenal cortex. These peroxisomes appear as small, elliptical to spherical or branched structures, enclosed by a single membrane and composed of a moderately electron-dense matrix. They do not possess a nucleoid or core of the type found in peroxisomes of liver and kidney. These organelles show a strongly positive staining reaction with the diaminobenzidine technique for peroxidatic activity of catalase. This staining is inhibited by aminotriazole. In cytochemical preparations revealing acid phosphatase activity, lysosomes are strongly stained and peroxisomes are free of reaction product.

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.

Plastoquinone-9 biosynthesis in cyanobacteria differs from that in plants and involves a novel 4-hydroxybenzoate solanesyltransferase

2012 ◽  
Vol 442 (3) ◽  
pp. 621-629 ◽  
Author(s):  
Radin Sadre ◽  
Christian Pfaff ◽  
Stephan Buchkremer
Keyword(s):  
Biosynthetic Pathway ◽  
In Vitro Assays ◽  
Transport Chain ◽  
In Vivo Labelling ◽  
Membrane Bound ◽  
Transformation Processes ◽  
Synechocystis Sp

PQ-9 (plastoquinone-9) has a central role in energy transformation processes in cyanobacteria by mediating electron transfer in both the photosynthetic as well as the respiratory electron transport chain. The present study provides evidence that the PQ-9 biosynthetic pathway in cyanobacteria differs substantially from that in plants. We identified 4-hydroxybenzoate as being the aromatic precursor for PQ-9 in Synechocystis sp. PCC6803, and in the present paper we report on the role of the membrane-bound 4-hydroxybenzoate solanesyltransferase, Slr0926, in PQ-9 biosynthesis and on the properties of the enzyme. The catalytic activity of Slr0926 was demonstrated by in vivo labelling experiments in Synechocystis sp., complementation studies in an Escherichia coli mutant with a defect in ubiquinone biosynthesis, and in vitro assays using the recombinant as well as the native enzyme. Although Slr0926 was highly specific for the prenyl acceptor substrate 4-hydroxybenzoate, it displayed a broad specificity with regard to the prenyl donor substrate and used not only solanesyl diphosphate, but also a number of shorter-chain prenyl diphosphates. In combination with in silico data, our results indicate that Slr0926 evolved from bacterial 4-hydroxybenzoate prenyltransferases catalysing prenylation in the course of ubiquinone biosynthesis.

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.

scholarly journals Adrenal Gland Toxicity: Chemically Induced Dysfunction

1988 ◽  
Vol 7 (1) ◽  
pp. 45-69 ◽  
Author(s):  
H. D. Colby
Keyword(s):  
Adrenal Cortex ◽  
Covalent Binding ◽  
Critical Role ◽  
Physiological Role ◽  
Metabolic Activation ◽  
Zona Fasciculata ◽  
Zona Reticularis ◽  
Hormone Synthesis ◽  
Chemically Induced ◽  
Endocrine Organs

Among the endocrine organs, the adrenal cortex appears to be the most vulnerable to chemically induced injury. A wide variety of chemicals has been found to cause morphological or functional lesions in the gland. Some of the lesions are highly localized to specific anatomical zones of the adrenal cortex, and the resulting functional deficits depend on the physiological role(s) of the zone affected. In addition, metabolic activation is an important factor contributing to the gland's vulnerability to chemical injury. For example, carbon tetrachloride (CCl4) causes adrenocortical necrosis, but only of the innermost zone of the gland, the zona reticularis. The apparent reason for the localized effect of CCl4 in the adrenal cortex is that only the cells of the zona reticularis have the enzymatic capacity to activate CCl4, resulting in lipid peroxidation and covalent binding to cellular macromolecules. By contrast, the mineralocorticoid antagonist, spironolactone, causes functional lesions in the adrenal cortex that are limited to the middle zone of the gland, the zona fasciculata. The explanation again involves metabolic activation; only the zona fasciculata converts spironolactone to a highly reactive metabolite that effects the destruction of several enzymes that are required for steroid hormone synthesis. These findings indicate that bioactivation plays a critical role in the mechanism(s) of action of various toxic agents on the adrenal cortex and also may be responsible for the anatomically localized effects of many chemicals.

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