Showing papers on "Adrenal cortex published in 1982"

Direct evidence that cholesterol ester hydrolase from adrenal cortex is the same enzyme as hormone-sensitive lipase from adipose tissue.

Abstract: Several properties of the cytosolic cholesterol ester hydrolase from bovine adrenal cortex were investigated and those properties were compared directly with those of the well-characterised hormone-sensitive lipase, the rate-limiting enzyme in adipose tissue lipolysis. Properties examined included: (a) activity against different substrates; (b) susceptibility to inhibition by NaF, Hg2+ ions and diisopropyl fluorophosphonate; (c) subunit molecular weight as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate; (d) ability to serve as a substrate for cyclic AMP-dependent protein kinase; (e) effect of phosphorylation on enzyme activity; and (f) degradation pattern of polypeptides following limited proteolysis. In all respects the two enzymes exhibited essentially identical characteristics. It is therefore concluded that the same protein, or two very similar proteins, catalyses the hydrolysis of cholesterol esters in adrenal cortex and lipolysis in adipose tissue. The implication of this finding is discussed in relation to the hormonal control of steroidogenesis in adrenal cortex and of lipolysis in adipose tissue.

Cytochrome P-45011 beta and P-450scc in adrenal cortex: zonal distribution and intramitochondrial localization by the horseradish peroxidase-labeled antibody method.

Abstract: In an attempt to elucidate the regulation mechanism(s) of adrenocortical steroidogenesis, cytochrome P-450scc and cytochrome P-45011 beta were localized in bovine adrenal glands by the direct peroxidase-labeled antibody method. At the light microscopic level, parenchymal cells of the zona fasciculata and the zona reticularis stained heavily for both cytochromes, while the parenchymal cells of zona glomerulosa stained lightly for both. At the electron microscopic level, these two cytochromes were associated with the matrix side of the inner mitochondrial membranes of parenchymal cells from all three zones of the adrenal cortex. The association of cytochrome P-450 with the inner mitochondrial membrane, in a manner similar to that previously reported for adrenodoxin and adrenodoxin reductase (F Mitani, Y Ishimura, S Izumi, K Watanabe, Acta Endocrinol 90:317, 1979), establishes that the steroid monooxygenase systems exist at this site. The degree of immunocytochemical staining within a single cell varied from one mitochondrion to another: some stained intensely along the entire inner membrane, including the cristae, some stained only along segments of the inner membrane, and some did not stain at all. This heterogeneity in staining was observed in mitochondria stained in situ as well as in isolated mitochondria. These findings suggest that there is a heterogeneity in steroidogenesis among mitochondria contained within a single cell of the adrenal cortex.

in Adrenal Cortex: Zonal Distribution and Intramitochondrial Localization by the Horseradish Peroxidase-labeled Antibody Method

Abstract: In an attempt to elucidate the regulation mechanism(s) of adrenocortical steroidogenesis, cytochrome P-4SOscc and cytochrome P-4501 ifi were localized in bovine adrenal glands by the direct peroxidase-labeled antibody method. At the light microscopic level, parenchymal cells of the zona fasciculata and the zona reticularis stained heavily for both cytochromes, while the parenchymal cells of zona glomerulosa stained lightly for both. At the electron microscopic level, these two cytochromes were associated with the matrix side of the inner mitochondrial membranes of parenchymal cells from all three zones of the adrenal cortex. The association of cytochrome P-450 with the inner mitochondrial membrane, in a manner similar to that previously reported for adrenodoxin and adrenodoxin reductase (F Mitani, Y Ishimura, S Izumi, K Watanabe, Acta

Hypersecretion of a new corticosteroid, 18-hydroxycortisol in two types of adrenocortical hypertension.

Abstract: The most abundant substance in the urinary free steroid fraction of patients with primary aldosteronism has been identified as 18-hydroxycortisol 18-hydroxycortisol is very likely an adrenocortical secretory product rather than a peripheral metabolite, since it is abundantly synthesized by aldosteronoma tissue slices The biogenesis of 18-hydroxycortisol takes place from cortisol rather than from 18-hydroxycorticosterone; that is, 17 alpha-precedes 18-hydroxylation Cortisol 18-hydroxylation appears to be unrelated to the two other types of adrenocortical hydroxylation at this position The pathway is present to a small extent in the normal human adrenal cortex and is only moderately stimulated by ACTH Cortisol 18-hydroxylation is markedly accentuated in two circumstances: in the aldosteronoma cell where its presence may serve to distinguish tumor from bilateral hyperplasia and in ACTH-stimulatable hyperaldosteronism where it represents the first qualitative steroid biochemical abnormality to be demonstrated and as such may be useful in diagnosis and genetic studies The possible contribution of 18-hydroxycortisol to the severity of the clinical manifestations of mineralocorticoid excess in these two types of aldosteronism remains to be explored

Beta-endorphin is present in the male reproductive tract of five species.

Abstract: Previous studies from this laboratory have demonstrated immunostainable beta-endorphin-like material (beta-EP) in Leydig cells and epithelia of the epididymis, seminal vesicle and vas deferens of the rat. These observations would be strengthened if it could be demonstrated that they were not a peculiarity of the rat. Accordingly, we now present immunocytochemical evidence for the presence of beta-EP in the Leydig cells of mouse, hamster, guinea pig and rabbit. No immunoreactive material was identified in Sertoli, myoid, endothelial or germ cells of any of the species examined. Immunostainable beta-EP was also demonstrated in the epididymides of mouse, guinea pig, rabbit, and rat, but not hamster. Immunostainable material was also present in the epithelia of the vas deferens and seminal vesicles of mouse and rat, the only two species thus far examined. Since beta-EP was present in Leydig cells, we wondered whether this peptide could be identified in other steroid-producing tissues. When rat ovaries and adrenals were reacted with anti-beta endorphin, staining was demonstrated in corpus luteum and adrenal cortex. No staining was observed in the adrenal medulla or other portions of the ovary. In order to determine whether the beta-EP detected in the testis and epididymis was derived from a pituitary source, animals were hypophysectomized and tissues examined 2 weeks later. Both the Leydig cells and the epididymal epithelium remained immunostainable. In summary, immunostainable beta-EP has been identified in Leydig cells of five species. Stainable material is also present in the epithelium of other portions of the male reproductive tract and in steroid-secreting cells of the ovary and the adrenal. Such beta-EP may have a paracrine function in the testis and other portions of the male reproductive tract.

Ontogeny of the corticoliberin neuroglandular system in rat brain

Abstract: Although it has long been known that the hypothalamus contains substances which stimulate the release of adrenocorticotropic hormone (ACTH)1,2, corticoliberin (CRF) has only recently been identified and synthesized3,4. Here we describe the results of immunocytochemical staining of the neuroglandular system using an antiserum raised against this synthetic peptide. Neurone bodies containing CRF-like immunoreactivity (CLI) were stained in the paraventricular nuclei (PVN) of colchicine-injected rats whereas in normal rats, CLI was detected only in nerve fibres. These CLI-positive processes were abundant in the zona externa of the median eminence and in the pituitary stalk; they terminated close to capillaries of the primary portal plexus. In the rat fetus, CLI-containing fibres were detected only after the 18th day of development. After birth, a transitory disappearance of CLI was followed by its accumulation in fibres and perikarya. Morphological and physiological results corroborate recent biochemical studies 3,4; these will have to be taken into account in studies of the phenomena implicating participation of the adrenal cortex.

The Control of Steroidogenesis by Human Fetal Adrenal Cells in Tissue Culture. IV.The Effects of Exposure to Placental Steroids

Abstract: The effect upon steroidogenesis of adding various steroids produced by the placenta was studied in short term cultures of human fetal adrenal cells. The addition of high concentrations (103 ng/ml) of estrone or estriol inhibited the production of cortisol, but only the former elicited a parallel increase in dehydroepiandrosterone (DHA) production. Estradiol was effective in inhibiting Δ4-3-ketosteroid production at concentrations of 10-100 ng/ml, levels which approach those found in the fetal circulation, while DHA production was increased at concentrations of 1 eg/ml. The addition of progesterone (4 eg/ml) to the medium caused increased production of cortisol and corticosterone, but had no effect on DHA production. Pregnenolone (4)eg/ml) increased the basal production of DHA and slightly impaired both basal and ACTH-stimulated aldosterone production, but had no effect on cortisol production. The data demonstrate that of the many fetal and placental factors which have been studied to date, only ACTH and e...

Adrenal Function in Heterozygous and Homozygous Hypobetalipoproteinemia

Abstract: Corticosteroid synthesis in the human adrenal cortex requires a supply of cholesterol which can be derived from both local synthesis and the uptake of plasma lipoproteins. Studies with cultured adrenal cells have shown that such uptake i s mediated through the interaction of plasma low density lipo-proteins (LDL) and a specific cellular receptor (the LDL receptor). In the present study we have examined parameters of adrenal corticosteroid production in a patient with phenotypic abetalipoproteinemia (on the basis of homozygous hypobetalip-oproteinemia) and in three of her relatives with inherently low levels of LDL (heterozygous hypobetalipoproteinemia). These studies sought to determine whether the absence of LDL or an inherent reduction in their plasma concentration results in alterations in corticosteroid production both under basal conditions and in response to prolonged stimulation with iv ACTH. Our results document normal parameters of corticosteroid production under basal conditions in both heterozy...

Markedly elevated specific renin levels in the adrenal in genetically hypertensive rats.

Abstract: The specific renin (EC 3.4.99.19) activity in the adrenal of spontaneously hypertensive rats was determined by a method that is capable of distinguishing renin from nonspecific renin-like activity of proteases by using specific antibody to renin. The renin level in the adrenals of adult spontaneously hypertensive rats with established hypertension was found to be 6-8 times as high as that of the normotensive control Wistar-Kyoto strain. The large difference in the adrenal renin level was observed even in 3-wk-old rats in which hypertension has not yet developed. The adrenal renin level was increased by bilateral nephrectomy in both the hypertensive and normotensive strains. A larger quantity of renin was found in the adrenal cortex than in the medulla, and the difference between the hypertensive strain and the normotensive strain was more prominent in the cortex than in the medulla. These results suggest possible involvement of adrenal renin in the development and in the early maintenance phase of hypertension in this animal mode of human essential hypertension by affecting the adrenocortical or adrenomedullary activity, or both.

Metyrapone and antioxidants are required to maintain aldosterone synthesis by cultured bovine adrenocortical zona glomerulosa cells.

Abstract: Bovine adrenal zona glomerulosa cell cultures were prepared by microdissection and collagenase digestion, followed by unit gravity sedimentation, to give populations of glomerulosa cells which were more than 95% pure. Glomerulosa cell-specific function was assayed by measuring the formation of [3H]aldosterone from saturating concentrations of precursor [3H] deoxycorticosterone and by measuring aldosterone production with a specific RIA. The purity of glomerulosa cell cultures was documented by demonstrating low levels of steroid 17α-hydroxylase activity, which is specific to the zona fasciculata-reticularis. [3H]Aldosterone production, expressed as a percentage of total 3H-labeled steroid products of [3H]deoxycorticosterone metabolism, decreased to 50% of the initial value within 12 h when cells were placed in primary culture. The following factors prolonged relative [3H]aldosterone synthesis: increasing cell density (>2 × 104 cells/cm2), lowering the oxygen concentration from 19% to 2% and including the ...

Development of adrenocortical failure in non-Addisonian patients with antibodies to adrenal cortex. A clinical follow-up study.

Abstract: SUMMARY Out of 1036 sera tested for the presence of antibodies to adrenal cortex using the indirect immunofluorescence (IFL) method, fifteen out of 323 patients with Graves' thyrotoxicosis, 6/105 Hashimoto's thyroiditis, 3/29 myxoedema, 2/49 asymptomatic autoimmune thyroiditis, 1/12 subacute thyroiditis, and 4/130 with myasthenia gravis were positive. Thirty antibody-positive non-addisonian patients were tested for subclinical adrenocortical failure and followed up over a period of 1–3–5 years. Three women with Graves' disease had biochemical signs of early Addison's disease at the first Synacthen test. Two young women with controlled Graves' thyrotoxicosis developed a diminished adrenocortical reserve within 2 and 3 years, respectively; one of them developed anovulatory cycles which did not respond to clomiphene treatment. Both patients had high titres of complement-fixing adrenal antibodies before the adrenal failure could be recognized by functional tests. One elderly female patient in whom a euthyroid goitre with adrenal and thyroid antibodies was detected in 1977, developed Graves' thyrotoxicosis in 1980. These observations indicate that antibodies to adrenal cortex have a high clinical significance and may allow the early diagnosis of Addison's disease even in the absence of specific clinical symptoms.

Response of the adrenal cortex to tetracosactrin (ACTH1-24) in the premature and full-term foal.

Abstract: The changes in plasma cortisol concentration in the immediate postnatal period were examined in 3 groups of newborn foals and the response of the adrenal cortex to exogenous ACTH1-24 (tetracosactrin) was tested in 2 of these groups. In full-term Thoroughbred and Pony foals a rise in plasma cortisol occurred between 0 and 30 min after birth, whereas no significant cortisol changes could be detected within 2 h of birth in the group of prematurely delivered foals. These differences in plasma cortisol between term and premature foals were accompanied by differences in blood pH and lymphocyte and neutrophil counts. The high cortisol concentrations in the term animals declined to low levels by 4-12 h after birth. There was also a clear distinction between the responsiveness of the adrenal cortex to ACTH in the term and premature animals. When short-acting tetracosactrin was given as a single i.m. injection (0.125 mg), a rapid rise in plasma cortisol occurred in all term foals whereas no response was detected in the premature group during the same 2-h test period. The adrenal cortical response was also accompanied by a significant fall in the neutrophil/lymphocyte ratio at 2 h after the injection; no such change was seen in the premature animals. After a 24-h period of treatment with depot tetracosactrin (3 doses; 0.4, 0.2, 0.2 mg i.m.), a 2nd test with short-acting tetracosactrin led to a rise in plasma cortisol in term and pre-term foals during the 2-h test period. The depot tetracosactrin also appeared to cause a 3-fold increase in basal plasma cortisol levels in both groups.

Regulation of 21-hydroxylase activity by steroids in cultured bovine adrenocortical cells: possible significance for adrenocortical androgen synthesis.

Abstract: When primary bovine adrenocortical cells were cultured in a serum- and lipoprotein-free medium, the pattern of steroids synthesized from pregnenolone precursor was altered by prior treatment with ACTH and by prior exposure to pregnenolone. As evidenced by the high performance liquid chromatographic profile of steroids synthesized from pregnenolone, ACTH induced 17-hydroxylase activity, whereas, regardless of ACTH treatment, prior exposure to pregnenolone reduced 21-hydroxylase activity. Direct addition of possible secreted products of pregnenolone—androstenedione, progesterone, and 17-hydroxyprogesterone (17-hydroxypregn-4-ene-3,20-dione)—was found to cause loss of 21-hydroxylase activity measured as 21-deoxycortisol (llβ,17-dihydroxypregn-4-ene-3,20-dione) conversion to cortisol. Several steroids that caused loss of 11β-hydroxylase activity did not affect 21-hydroxylase. Androstenedione suppressed both 21- and llβ-hydroxylase but did not affect 17-hydroxylase or C17,20-lyase activities. The time course o...

Compartmentalization of corticotropin-dependent steroidogenic factors in adrenal cortex: evidence for a post-translational cascade in stimulation of the cholesterol side-chain split

Abstract: A sensitive cell-free assay was developed for the analysis of corticotropin-dependent factors that stimulate the rate-limiting step of adrenal steroidogenesis. In this assay adrenal post-mitochondrial supernates from corticotropin-stimulated rats caused a 10- to 100-fold increase in the de novo synthesis of pregnenolone and progesterone. A similar stimulation was observed by corresponding fractions from Leydig cells and mouse Y-1 adrenal tumor cells, but not from rat liver. Subcellular fractionation of rat adrenal tissue showed several steroidogenic factors to be present in various compartments. Recombination of them produced highly synergistic effects. The activation of some components could also be demonstrated in vitro, suggesting a cascade of events possibly linking the cAMP-dependent phosphorylation pathway with the rate-limiting step. Cycloheximide prevented the production of these steroidogenic factors in vivo upon stimulation but had no effect in vitro, suggesting a post-translational cascade involved in the activation of the cholesterol side-chain split.

Progressive adrenal failure in polyglandular autoimmune disease.

Abstract: We describe the clinical course of a boy who developed progressive adrenal failure, beginning with failure of the zona glomerulosa, as part of polyglandular autoimmune disease. Initially the patient presented with hypoparathyroidism and mucocutaneous candidiasis. ACTH tests at ages 8 and 11 yr resulted in a normal response of both mineralo-and glucocorticoids. The constellation of hyponatremia, hyperkalemia, and growth failure at age 14 yr prompted a reevaluation. A repeat ACTH test, assessing individual contributions of zone fasciculata and glomerulosa, showed normal plasma cortisol, desoxycorticosterone, and corticosterone responses and a normal urinary response of 18-hydroxydeoxycorticosterone and tetrahydrodeoxycorticosterone. Urinary 18-hydroxycorticosterone and urinary as well as plasma aldosterone were undetectable. PRA was markedly elevated. The ACTH response of adrenal androgens, presumably metabolic products of the zona reticularis, was also deficient. Antiadrenal antibodies against all three la...

Preliminary observations on the role of the mesonephros in the development of the adrenal cortex.

Abstract: The interrelationship between mesonephros, adrenal cortex, and gonads was studied in 28- and 31-day old sheep fetuses by means of light microscopy on plastic sections. At these stages, the adrenal cortex is just beginning to develop and the mesonephros is undergoing involution; its regression is accompanied by mobilization of cells from the glomerulus of a peculiar nephron situated in the proximal third of the organ, and referred to as “giant” because of its large size. The mobilized cells egress from this glomerulus organized in trabeculae, some of which reach the cranial extremity of the adrenal cortex while others coalesce into a prominent cellular formation which extends uninterrupted toward and into the developing gonads. In previous studies we have shown that the mesonephric cells which colonize the gonads differentiate into sustentacular and interstitial steroidogenic cells; the presence of an analogous cellular migration from the mesonephros to the adrenal cortex now suggests that also the adrenal cortical cells may be of mesonephric origin.

Potential tumor- or organ-imaging agents. 23. Sterol esters of iopanoic acid.

Abstract: A series of sterol esters of iopanoic acid was synthesized and evaluated for their potential to selectively localize in liver and steroid-secreting tissues for possible application in either computed tomography or nuclear medicine imaging. Unlike free iopanoic acid (1), which was rapidly cleared following intravenous administration to rats, cholesteryl iopanoate (2) was found to accumulate in liver, adrenal cortex, and ovary. At 24 h, the ovary was found to contain the highest concentration of 2. The ability of 2 to accumulate in the above tissues was attributed to its resistance to hydrolysis. Pregnenolone iopanoate (3) and dehydroepiandrosterone iopanoate (4), on the other hand, were shown to reach unusually high concentrations in the adrenal cortex within 0.5 h of administration but declined to much lower levels by 24 h. Lipid extraction of tissues showed 3 and 4 to be susceptible to in vivo hydrolysis, which undoubtedly was a major factor in their clearance from adrenal tissue.

Feedback Actions of Adrenal Steroid Hormones

Abstract: The earliest work on the ways in which corticosteroids might influence the functional activity of the pituitary adrenocortical system was reported by Ingle and Kendall (1937). They showed that the administration of adrenocortical extracts to intact rats resulted Departments of Physiology, Biochemistry1, and Pharmacology2, St. Thomas’s Hospital Medical School, Lambeth Palace Road, London SEI 7EH, Great Britain in adrenocortical atrophy, whilst the simultaneous injection of an anterior pituitary extract with that from the adrenal cortex prevented the atrophic response (Ingle and Kendali 1937; Ingle et al. 1938). Subsequently, Deane and Greep (1946) showed that hypophysectomy results in atrophy of the zonae fasiculata and reticularis but the zona glomerulosa was virtually unaffected. A similar histologic picture was described by Winter et al. (1950) following prolonged treatment with Cortisone. Their results suggested that corticosteroid treatment inhibits adrenocorticotrophin (ACTH) secretion and the possibility that ACTH secretion could be regulated by adrenocortical secretions.