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Showing papers on "Adrenal cortex published in 1985"


Journal ArticleDOI
TL;DR: The results indicate that ANF may have important hemodynamic effects in kidney, lung, liver and adrenal cortex, may regulate water and ion transport in small intestine and ciliary bodies and may have metabolic effects in the liver.
Abstract: Rats were injected either with synthetic125I-Arg 101-Tyr 126 atrial natriuretic factor (ANF) or with125I-ANF together with an excess of cold Arg 101-Tyr 126 ANF. Binding sites in various tissues were accepted depending on two criteria: displacement of radioactivity by cold ANF and absence of localization of silver grains on putative target cells in the presence of cold ANF. Binding sites were localized on zona glomerulosa cells and on adrenergic and noradrenergic cells of adrenal medulla, on hepatocytes, on the base of mature epithelial cells of villi in the small intestine, on smooth muscle cells of the muscularis layer of the colon and on the base of epithelial cells of the ciliary bodies. In addition, binding sites were localized in the vasculature of kidney, adrenal cortex, lung and liver. Binding sites were particularly numerous on renal glomerular endothelial cells. These results indicate that ANF may have important hemodynamic effects in kidney, lung, liver and adrenal cortex, may regulate water and ion transport in small intestine and ciliary bodies and may have metabolic effects in the liver. The presence of binding sites on the zona glomerulosa is in agreement with the important inhibitory effect of the peptide on aldosterone secretion.

282 citations


Journal ArticleDOI
TL;DR: A differential and discrete localization of peripheral-type benzodiazepine receptors in rat pituitary, adrenal, and testis is demonstrated.
Abstract: We have used [3H]Ro5-4864, a ligand selective for peripheral-type benzodiazepine receptors, to identify and localize peripheral-type benzodiazepine receptors in endocrine organs. Autoradiographic studies reveal an uniform distribution of [3H]Ro5-4864 binding sites within the anterior, intermediate, and posterior lobes of the pituitary gland, with highest concentrations present in the posterior pituitary. In rat adrenal gland, specific binding sites for [3H]Ro5-4864 are found only in the adrenal cortex, with highest density in the zona glomerulosa and significantly lower concentrations in the zona fasciculata and zona reticularis. [3H]Ro5-4864-associated silver grains in the testis are intensely localized over the interstitial tissue; low concentrations of silver grains are present over the epithelium of the seminiferous tubules but are absent from the tubular lumen. These studies demonstrate a differential and discrete localization of peripheral-type benzodiazepine receptors in rat pituitary, adrenal, and testis.

260 citations


Journal Article
TL;DR: The search for a neurohormone specifically controlling ACTH secretion resulted in the discovery of the corticotropin-releasing factor, which is the predominant component of a complex control system of adrenal cortex secretion, which also includes catecholamines and the antidiuretic hormone.
Abstract: The search for a neurohormone specifically controlling ACTH secretion resulted in the discovery of the corticotropin-releasing factor (CRF). This factor, located mainly in a paraventricular-infundibular hypothalamic tract, stimulates ACTH synthesis and secretion through a cAMP-dependent mechanism. The corticotropin-releasing factor is the predominant component of a complex control system of adrenal cortex secretion, which also includes catecholamines and the antidiuretic hormone. Its specificity as stimulant of the corticotropic function makes it an extremely useful tool for physiological and physiopathological studies of the hypothalamus-pituitary-adrenal cortex axis regulation.

185 citations


Journal ArticleDOI
TL;DR: Binding sites for inositol trisphosphate (IP3) have been identified in bovine adrenal cortex, employing [32P]IP3 prepared from human erythrocytes radiolabeled with ATP as mentioned in this paper.

123 citations


Journal ArticleDOI
29 Mar 1985-Science
TL;DR: The results indicate that the blood-brain barrier may be hormonally regulated; that is, the pituitary-adrenal axis may physiologically modulate the permeability of the brain microvasculature to macromolecules.
Abstract: The blood-brain barrier restricts the passage of molecules from the blood to the brain. The permeability of the barrier to iodine-125-labeled bovine serum albumin was examined in rats that had undergone adrenalectomy, adrenal demedullation, and corticosterone replacement. Adrenalectomy, but not adrenal demedullation, increased the permeability of brain tissue to the isotopically labeled macromolecule; corticosterone replacement reversed this effect. These results indicate that the blood-brain barrier may be hormonally regulated; that is, the pituitary-adrenal axis may physiologically modulate the permeability of the brain microvasculature to macromolecules.

119 citations


Journal ArticleDOI
TL;DR: The results suggest that after induction of anaesthesia with a single bolus of etomidate, inhibition of other enzymes in the corticosteroid‐synthetic pathway (e.g. cholesterol‐side‐chain cleavage enzyme) is of little clinical relevance.
Abstract: In a prospective controlled trial we investigated the effect of an induction dose of etomidate (0.26 mg/kg i.v.) on plasma ACTH, progesterone, 17 alpha OH-progesterone, 11-deoxycortisol, cortisol, cortisone, corticosterone, 11-deoxycorticosterone, and aldosterone in seven males undergoing general anaesthesia. Seven other male patients receiving thiopentone at induction (5.0 mg/kg i.v.) served as controls. Plasma ACTH concentrations rose higher in the etomidate group (346 +/- 124 vs. 117 +/- 74 pg/ml, mean +/- SEM), but the difference was not significant. After etomidate we found a clear suppression of plasma cortisol (P less than 0.01), cortisone (P less than 0.01), corticosterone (P less than 0.01), and aldosterone (P less than 0.05) compared to corticosteroid levels after induction with thiopentone. Plasma 11-deoxycortisol and 11-deoxycorticosterone concentrations were grossly elevated 210 min after etomidate (91 +/- 28 nmol/l and 7.04 +/- 0.47 nmol/l, respectively, P less than 0.01) demonstrating inhibition of 11 beta-hydroxylation of both glucocorticoid and mineralocorticoid intermediates. In contrast, no significant difference in plasma progesterone and 17 alpha-OH-progesterone levels was found between the two groups indicating that the cholesterol-side-chain cleavage enzyme is less sensitive to etomidate than 11 beta-hydroxylase. Our results suggest that after induction of anaesthesia with a single bolus of etomidate, inhibition of other enzymes in the corticosteroid-synthetic pathway (e.g. cholesterol-side-chain cleavage enzyme) is of little clinical relevance.

103 citations


Journal ArticleDOI
TL;DR: Neuropeptide Y (NPY) distribution in bovine adrenal glands was studied by RIA and immunohistochemical technique and biochemical characterization by HPLC revealed two major NPY immunoreactive peptides.
Abstract: Neuropeptide Y (NPY) distribution in bovine adrenal glands was studied by RIA and immunohistochemical technique. NPY content (picomoles per mg protein ± SEM) of chromaffin cells, medulla, cortex, and whole glands was 4.2 ± 0.16, 2.7 ± 0.28, 0.19 ± 0.02, and 0.94 ± 0.14, respectively, while the chromaffin granule NPY content was 53. Immunohistochemically, NPY immunoreactivity was detected in norepinephrine containing chromaffin cells and also in nerve fibers crossing through adrenal cortex and medulla. NPY and enkephalin immunoreactivities were found in distinct chromaffin cells. Biochemical characterization by HPLC revealed two major NPY immunoreactive peptides. The most abundant molecular form was identified as authentic NPY. (Endocrinology 117: 1162–1168, 1985)

90 citations


Journal ArticleDOI
TL;DR: The transferase was not observed in mitochondria, Golgi apparatus, lysosomes, peroxisomes, and plasma membrane, even after 3- to 4-fold induction of various substrate-specific UDPglucuronosyltransferase activities.
Abstract: UDPglucuronosyltransferase [UDPglucuronate beta-D-glucuronosyltransferase (acceptor-unspecific), EC 2.4.1.17] is a group of enzymes with distinct but partially overlapping substrate specificity. A rabbit antiserum raised against one purified rat liver UDPglycuronosyltransferase isoform was specific for UDPglucuronosyltransferase and recognized all transferase isoforms by immunodiffusion or immunotransblot analysis. The transferase activity toward all substrates was immunoabsorbed from solubilized rat liver microsomes by IgG purified from the antiserum. The purified IgG was used for immunocytochemical localization of UDP-glucuronosyltransferase in rat liver, jejunum, kidney, and adrenal gland. In the liver, UDPglucuronosyltransferase was present exclusively in hepatocytes and was uniformly distributed within all zones of the hepatic lobule. In the jejunum, the transferase was present exclusively in the epithelial cells and showed a progressive increase in concentration from the crypt to the villar tip. In the kidney, the greatest concentration of the transferase was observed in the epithelial cells of the proximal convoluted tubule. Adrenal medullary cells showed intense immunocytochemical staining; the zona glomerulosa and the zona reticularis of the adrenal cortex were more intensely stained than the zona fasciculata. By light microscopy, UDPglucuronosyltransferase was found in the endoplasmic reticulum and nuclear envelope of all the four organs; this was confirmed in the hepatocyte by electron microscopy. The transferase was not observed in mitochondria, Golgi apparatus, lysosomes, peroxisomes, and plasma membrane, even after 3- to 4-fold induction of various substrate-specific UDPglucuronosyltransferase activities.

88 citations


Journal ArticleDOI
TL;DR: The present data suggest that the rate of resynthesis of polyphosphoinositides also increases shortly after the activation of PtdIns4,5P2 phosphodiesterase, and indicates that the production rate of inositol tris- and bisphosphate shows a manifold increase in the first seconds of stimulation and remains enhanced for at least several minutes.

80 citations


Journal ArticleDOI
TL;DR: The results suggest that conversion of corticosterone and of 18-hydroxycorticosterone to aldosterone occurs through P-45011 beta-catalyzed reaction.
Abstract: When corticosterone was incubated with cytochrome P-45011 beta purified from bovine adrenocortical mitochondria in the presence of adrenodoxin, NADPH-adrenodoxin reductase and an NADPH generating system, aldosterone as well as 18-hydroxycorticosterone were formed with turnover numbers of 0.23 and 1.1 nmol/min/nmol P-450, respectively. Phospholipids extracted from adrenocortical mitochondria remarkably enhanced the activity of aldosterone formation by the cytochrome P-45011 beta-reconstituted system. The apparent Km and turnover number were estimated to be 6.9 microM and 2.0 nmol/min/nmol P-450 for aldosterone formation in the presence of the lipidic extract. When 18-hydroxycorticosterone was tested as a substrate, cytochrome P-45011 beta showed catalytic activity for aldosterone synthesis with an apparent Km and turnover number of 325 microM and 5.3 nmol/min/nmol P-450, respectively. Carbon monoxide and metyrapone inhibited the production of aldosterone from corticosterone and that from 18-hydroxycorticosterone. These results suggest that conversion of corticosterone and of 18-hydroxycorticosterone to aldosterone occurs through P-45011 beta-catalyzed reaction.

80 citations


Book ChapterDOI
01 Jan 1985
TL;DR: The adrenal cortex exhibits a unique system of physiological regulation, incorporating three separately regulated systems of hormone synthesis—mineralocorticoid, glucocortioid, and androgen—into the life history of a single cell type.
Abstract: Publisher Summary The regulation of the structure of the mammalian adrenal cortex is an intrinsic component of the regulation of the synthesis of its steroid hormones. The two important structural factors to be considered are (1) adrenocortical mass and (2) zonation. Adrenocortical structure is involved in the regulation of the synthesis of the mineralocorticoid, glucocorticoid, and androgenic steroids secreted by the adrenal under both normal and pathological conditions. The adrenal cortex exhibits a unique system of physiological regulation, incorporating three separately regulated systems of hormone synthesis—mineralocorticoid, glucocorticoid, and androgen—into the life history of a single cell type. The adrenal glands vary in shape from almost spherical, in fetal life and in the adult of some species, through somewhat flattened to more or less leaf-like, for example, in humans and cattle. Although the size of the gland varies with the size of the animal, the thickness of the cortex remains remarkably constant. The mass of the zona glomerulosa is a major factor in the long-term regulation of aldosterone synthesis, and the inner zone (zona reticularis or fetal zone) is of major importance for the regulation of adrenal androgen synthesis.

Journal ArticleDOI
TL;DR: Renin immunoreactivity was found in some large cells of the anterior pituitary, theZona glomerulosa and the zona reticularis of the adrenal, the Leydig cells ofthe testis, and the follicular epithelial cells ofThe thyroid and prostate glands.
Abstract: The peroxidase-labeled antibody method and the avidin-biotin-complex method with antiserum to purified human kidney renin were used to identify renin in humanendocrine tissues. Renin immunoreactivity was found in some large cells of the anterior pituitary, the zona glomerulosa and the zona reticularis of the adrenal, the Leydig cells of the testis, and the follicular epithelial cells of the thyroid and prostate glands. The specificity of the immunohistochemical reaction was confirmed by immunoabsorption tests. The specific localization of immunoreactive renin in each tissue suggests a possible role of renin in the function of these tissues.

Journal ArticleDOI
TL;DR: The anatomical substrate for the catecholaminergic innervation of the rat adrenal cortex is established, and nerve fibers and varicosities found to contain small clear vesicles as well as large (60–110 nm) and small (30–60 nm) dense-coredVesicles which are thought to contain Catecholamines.
Abstract: The zona glomerulosa of the rat adrenal gland is innervated by catecholaminergic nerves. Using histofluorescence techniques, we observed catecholaminergic plexuses surrounding adrenal capsular and subcapsular blood vessels. Individual varicose nerve fibers that branched off these plexuses were distributed among adrenal glomerulosa cells. This innervation was permanently eliminated after neonatal sympathectomy with guanethidine or 6-hydroxydopamine, but was not affected by ligation of the splanchnic nerve or extirpation of the suprarenal ganglion. At the ultrastructural level, axonal varicosities were commonly observed in close proximity to glomerulosa cells and blood vessels. Nerve fibers and varicosities were found to contain small (30–60 nm) clear vesicles as well as large (60–110 nm) and small (30–60 nm) dense-cored vesicles. In tissue fixed for the dichromate reaction with or without pretreatment with the false transmitter 5-hydroxydopamine, many nerve terminals contained numerous small dense-cored vesicles which are thought to contain catecholamines. These results establish the anatomical substrate for the catecholaminergic innervation of the rat adrenal cortex.

Journal ArticleDOI
TL;DR: While corticosterone is a major product of glomerulosa tissue in vitro, the available evidence suggests that it is not a major glomersulosa product in vivo.
Abstract: The study of the control of aldosterone synthesis and secretion by the rat adrenal gland has over the past thirty years involved the application of many different in vivo and in vitro techniques. In this review the relationship between the data that each of these methods has produced is compared. There are striking differences in overall steroid production rates, and in the qualitative nature of the steroid profile which the various methods produce. In particular, aldosterone is secreted at higher rates in vivo, and when whole tissue preparations are used in vitro, than in incubations of isolated glomerulosa cells. In addition, while corticosterone is a major product of glomerulosa tissue in vitro, the available evidence suggests that it is not a major glomerulosa product in vivo.

Journal ArticleDOI
TL;DR: This is the first demonstration of a dissociation between concentrations of cortisol and an adrenal androgen due to psychological stress in patients recovering from acute surgical stress.
Abstract: Patients recovering from acute surgical stress often excrete increased 17-OH corticosteroids with no change in 17-ketosteroids. The explanation for these findings is unclear. In order to investigate possible divergence between cortisol and adrenal androgen metabolism in acute stress, repeated morning cortisol and dehydroepiandrosterone (DHA) measurements were made in patients undergoing ACTH stimulation 48 to 96 hours preoperatively, followed by determinations before and during major surgery, also performed in the morning. Cortisol and DHA are largely metabolized by the liver, so liver blood flow under a constant general anesthetic regimen known not to affect cortisol metabolism was monitored by pre- and intraoperative indocyanine green dye clearance. Results indicated no difference between the cortisol and DHA stimulation resulting from two hours of ACTH stimulation or major surgery, and a small (14.4%) decline in hepatic blood flow during general anesthesia. However, while DHA concentrations remained constant immediately preceding surgery, cortisol concentrations increased by 61% (P less than 0.05). Previous studies have also demonstrated increased concentrations of cortisol before surgical procedures, presumably due to psychological stress. However, this is the first demonstration of a dissociation between concentrations of cortisol and an adrenal androgen due to psychological stress.

Journal ArticleDOI
TL;DR: Hypothalami, anterior pituitary gland segments and adrenal glands were removed from female Wistar-derived rats decapitated at various times of the day to study the effects of decapitation on hypothalami and tissue hormone concentrations.
Abstract: Hypothalami, anterior pituitary gland segments and adrenal glands were removed from female Wistar-derived rats decapitated at various times of the day. Blood and tissue hormone concentrations were measured and the tissues challenged with appropriate stimuli in vitro. Both bioactive and immunoreactive corticotrophin-releasing factor (CRF) content of the hypothalami were significantly higher in the evening than in the morning, as was the basal release of bioactive CRF in vitro. The response of the hypothalami to serotonin or acetylcholine added in vitro did not change with time of day. Basal bioactive and immunoreactive adrenocorticotrophin (ACTH) release from the anterior pituitary gland was significantly increased in the evening, as was the response to synthetic ovine CRF in vitro. Plasma ACTH concentrations in intact rats given crude CRF (hypothalamic extract) in vivo were higher in the evening at all times after injection tested, but this difference was markedly reduced in animals with mediobasal hypothalamic lesions. Corticosterone released basally from adrenal glands in vitro was significantly increased in the evening and the response to added ACTH 1–24 was slightly enhanced. For adrenal glands removed from lesioned rats, the pattern was reversed, corticosterone release in vitro being lower in the evening for all doses of ACTH added. Similarly in vivo, in intact rats given ACTH 1–24, plasma corticosterone concentrations and corticosterone release in vitro from adrenal glands removed after the injection were higher in the evening. After the placement of basal hypothalamic lesions, the situation was reversed, the response to ACTH administration in vivo being greater in the morning. The peaks in plasma concentrations of ACTH and corticosterone occurred 1 h later than the peak in hypothalamic CRF release. Therefore, it appears that the timing of the diurnal variation in plasma levels is dictated by the hypothalamus, but circadian changes in the output and responsiveness of the pituitary gland to CRF and the adrenal glands to ACTH play a major role in determining the amplitude of the rhythm.

Journal ArticleDOI
TL;DR: These studies confirm the same degree of specificity of HDL3 binding found with cultured adrenal cells and strengthen the suggested existence of a specific HDL receptor.

Book ChapterDOI
01 Jan 1985
TL;DR: If the effects of cortisol on the immune system can be defined, then the other effects of stress on host defense mechanisms, which may be unique to specific stressors and superimposed on the cortisol effect, can be better understood.
Abstract: Stress is a term used to describe a wide variety of adverse external influences on an animal. Some researchers consider stress to be the internal manifestation of the external influence, or “stressor.” There is no general agreement as to what constitutes a stress on an animal or how stress should be defined (29). It is clear, however, that stress can lead to increased susceptibility to disease and that the increased susceptibility is partially due to alterations in immune function (47). Other chapters in this book address stress-induced alterations in the immune system and illustrate the complexity of the effects of various stressors. To understand the effects of stress on the immune system it is important to study individual mechanisms of stress-induced immunosuppression. Perhaps the easiest mechanism to separate and define is the immunosuppression caused by increased plasma cortisol concentrations. A general response of the body to stress is the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland, which stimulates the adrenal cortex to increase the synthesis and secretion of cortisol (hydrocortisone). If the effects of cortisol on the immune system can be defined, then the other effects of stress on host defense mechanisms, which may be unique to specific stressors and superimposed on the cortisol effect, can be better understood.

Journal ArticleDOI
TL;DR: A role for cAMP-mediated events in the regulation of cytochrome P-450(11)beta gene expression is suggested, together with previous studies that showed increased intracellular levels of cAMP upon treatment of bovine adrenocortical cell cultures with ACTH, are suggested.

Journal ArticleDOI
TL;DR: TMB-8 inhibits aldosterone secretion without inhibiting mobilization of calcium from an intracellular pool, but this drug also inhibits the activity of protein kinase C directly.
Abstract: The mechanism of 8-(NN-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8) action was evaluated in isolated adrenal glomerulosa cells. TMB-8 inhibits both angiotensin II- and K+-stimulated aldosterone secretion in a dose-dependent manner. The ID50 for angiotensin II- and K+-stimulated aldosterone secretion is 46 and 28 microM, respectively. In spite of the fact that 100 microM-TMB-8 inhibits angiotensin II-stimulated aldosterone secretion almost completely, TMB-8 (100 microM) does not inhibit angiotensin II-induced 45Ca2+ efflux from prelabelled cells nor does it affect inositol 1,4,5-trisphosphate-induced calcium release from non-mitochondrial pool(s) in saponin-permeabilized cells. TMB-8 has no inhibitory effect on A23187-induced aldosterone secretion, but 12-O-tetradecanoylphorbol 13-acetate-induced aldosterone secretion is completely abolished. TMB-8 effectively inhibits both angiotensin II- and K+-induced increases in calcium influx but has no effect on A23187-induced calcium influx. TMB-8 inhibits the activity of protein kinase C dose-dependently. These results indicate that TMB-8 inhibits aldosterone secretion without inhibiting mobilization of calcium from an intracellular pool. The inhibitory effect of TMB-8 is due largely to an inhibition of plasma membrane calcium influx, but this drug also inhibits the activity of protein kinase C directly.

Journal ArticleDOI
TL;DR: Data show that functionally active V1 receptors are present in rat glomerulosa cells, and suggest that vasopressin may regulate the function of the adrenal glomersulosa.
Abstract: Specific, high affinity sites that bound tritium-iabeled arginine-vasopressin (3H-AVP) were detected in a crude membrane fraction of rat adrenal capsules (chiefly zona glomerulosa). Binding displacement experiments with peptide analogs of AVP suggested that the binding site is a pressor (V1 type receptor for AVP. When added to dispersed rat adrenal glomerulosa cells, vasopressin (10−810−6 M) stimulated the incorporation of 32P-phosphate into phosphatidylinositol, and the effect was blocked by the AVP receptor antagonist peptide d(CH2)5Tyr(Me)AVP. Vasopressin also increased the breakdown of phosphatidylinositol-4,5-bisphosphate within 1 min after its addition to the incubation medium. Superfused zona glomerulosa cells responded to AVP(10−810−6 M) by increasing their aldosterone production. The response could be blocked by the antagonist peptide. These data show that functionally active V1 receptors are present in rat glomerulosa cells, and suggest that vasopressin may regulate the function of the adrenal g...

Journal ArticleDOI
TL;DR: It was demonstrated unequivocally by various approaches that the ATP-dependent proteolytic activity localizes in mitochondrial matrix, similar to that of cytochrome oxidase and succinate dehydrogenase.

Journal ArticleDOI
TL;DR: Results indicate that 5-LO pathway is present in rat adrenocortical cells and its metabolites, most likely 5-HPETE, may play an important role in adrenal steroidogenesis.

Journal ArticleDOI
TL;DR: In the luteal phase, although the plasma 17-hydroxyprogesterone level at 30 min was higher, a response to ACTH was not consistently found, in contrast to the consistent 52 +/- 15 ng/dl response in the follicular phase.
Abstract: ACTH tests were performed with and without dexamethasone (dex) pretreatment to clarify the nature of the relationship between the absolute and incremental response (Δ) to ACTH in normal men and women, hirsute women, adrenarchal children, and women heterozygous for congenital adrenal hyperplasia (CAH). The purposes were to test the effect of dex preparation on adrenal responsiveness to ACTH and the efficacy of the dex-pretreated ACTH test in detecting heterozygosity for CAH. Cosyntropin was given as a 10 μg⁄m2 iv bolus dose at 0800-1000 h; dex (1 mg⁄m2) was given at 2200-2400 h the night before. Dex did not alter the absolute plasma steroid levels achieved in response to ACTH. However, since post-dex baseline concentrations of adrenal steroids were lower, the Δ to ACTH was significantly greater for the major adrenal secretory products, 17«-hydroxypregnenolone (3β,17α-dihydroxypregn-5-ene-20- one), dehydroepiandrosterone, and cortisol (F). For example, for all paired tests, the mean plasma F values achieved...

Journal Article
TL;DR: Interestingly, many benign adrenal cortical tissues and some carcinomas lacked immunoreactivity for all types of IF, suggesting a poorly developed IF system in these tissues, which apparently can be distinguished from each other with antibodies to intermediate filament proteins.
Abstract: Normal adrenal glands (10 specimens) and adrenal gland tumors (58 cases) were immunohistochemically evaluated for different types of intermediate filament (IF) proteins. Some of the normal cortical cells showed cytokeratin positivity, and no positivity was seen for epidermal keratin or other types of IF. In the adrenal medulla, neurofilament positivity was seen in nerve axons, some ganglion cells, and chromaffin cells; and cytokeratin-positive cells could not be detected. Only the vascular and connective tissue elements showed vimentin positivity in both cortical and medullary areas. In half of the cortical carcinomas (13/25), cytokeratin-positive tumor cells were found. Furthermore, vimentin-positive tumor cells were present in 10 of 25 cases, in some of them together with cytokeratin-positive cells. Thus, the results show heterogeneity among the adrenal cortical carcinomas. Interestingly, many benign adrenal cortical tissues and some carcinomas lacked immunoreactivity for all types of IF, suggesting a poorly developed IF system in these tissues. In contrast to adrenal cortical tumors, pheochromocytomas contained neurofilamentlike immunoreactivity. These results reflect the different cellular nature of adrenal cortical and medullary tumors, which apparently can be distinguished from each other with antibodies to intermediate filament proteins.

Journal ArticleDOI
TL;DR: It seems unlikely that the decrease in the cortisol level after prolonged stress was caused by exhaustion of the adrenal cortex, and some central mechanisms which could account for the biphasic changes in the plasma cortisol level and for disturbances of the hormone diurnal rhythmicity under conditions of prolonged stress are discussed.
Abstract: Diurnal variations in the plasma cortisol level were studied in anoestrous, pro-oestrous and pregnant ewes subjected to weak electric stimulation of the fore-limbs 9 h daily for 3 consecutive days. In non-pregnant ewes the cortisol level rose on each of the 3 days when the stimulation was applied and then decreased on the day following the stimulation. A similar decrease in plasma cortisol concentrations in pregnant ewes appeared on the second day of footshocking. The acrophase of the circadian rhythm on electrostimulation days was synchronous with the time of application of footshocks; therefore, in stimulated ewes it was significantly accelerated compared to the prestimulatory day. A decrease in the plasma cortisol level in pro-oestrous and pregnant ewes was accompanied by disappearance of its normal rhythmicity. Since a normal plasma cortisol response to exogenous corticotrophin was noted after 3 days of footshocking it seems unlikely that the decrease in the cortisol level after prolonged stress was caused by exhaustion of the adrenal cortex. Some central mechanisms which could account for the biphasic changes in the plasma cortisol level and for disturbances of the hormone diurnal rhythmicity under conditions of prolonged stress are discussed.

Journal ArticleDOI
TL;DR: It is proposed as a working hypothesis that these changes reflect a hormonally regulated alteration in the relationship between the outer and inner mitochondrial membranes, which may facilitate the rate-limiting movement of cholesterol from the outer to the inner membrane where the side chain cleavage enzyme is located.

Journal ArticleDOI
TL;DR: Although the clinical presentation of boys with PA is similar to that of girls with PA, there is a significant difference in the adrenal steroid secretory response to ACTH, and the biochemical events that cause PA in boys may be different from the corresponding events in girls.
Abstract: The adrenal secretory response to an iv bolus dose of ACTH was measured in 10 girls (4-8 yr of age), 5 boys (4-9 yr) with premature adrenarche (PA), and 20 normal children. The evening before the ACTH test, each subject took dexamethasone (1 mg at bedtime) to suppress the early morning surge of ACTH. The next morning, 2 serum samples were obtained before the administration of ACTH (Cortrosyn; 0.25 mg), and 2 samples were collected 30 and 45 min after ACTH administration. All samples were assayed for cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, 17-hydroxyprogesterone (17-OHP), and androstenedione. There was no significant difference in the dexamethasone-suppressed steroid levels between the children with PA and the normal children. After ACTH injection, cortisol, DHEA, 17-OHP, and androstenedione increased significantly. There was no significant change in DHEA sulfate. The mean 17-OHP response to ACTH in girls with PA was significantly higher than that in girls and women whose pubertal development was normal. This response was similar in magnitude to that in a group (n = 5) of obligate heterozygotes for congenital adrenal hyperplasia (CAH). These data suggest that many girls with PA have a mild adrenal steroid secretory defect that resembles the response in adult obligate heterozygotes for CAH due to 21-hydroxylase deficiency. In contrast to the girls, none of the boys with PA had an exaggerated 17-OHP response to ACTH. Thus, these boys had no evidence for an adrenal steroid secretory defect. In summary, although the clinical presentation of boys with PA is similar to that of girls with PA, there is a significant difference in the adrenal steroid secretory response to ACTH. Thus, the biochemical events that cause PA in boys may be different from the corresponding events in girls.

Journal ArticleDOI
TL;DR: It is concluded that clinically effective doses of mevinolin do not affect corticosteroid production by the adrenal cortex during prolonged ACTH stimulation in patients with heterozygous familial hypercholesterolemia.
Abstract: The biosynthesis of adrenal corticosteroids in humans depends on a continuous supply of cholesterol, which can be derived from both local synthesis and receptor-mediated uptake of low density lipoproteins (LDL) from plasma. Mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase [mevalonate:NAD+ oxidoreductase (CoA-acylating), EC 1.1.1.88] is an effective hypolipidemic agent in patients with heterozygous familial hypercholesterolemia. To determine whether mevinolin influences the adrenal production of corticosteroids, the adrenocortical response to a continuous 36-hr infusion of corticotropin (ACTH) was examined in eight patients with heterozygous familial hypercholesterolemia before, and again during, treatment with mevinolin (40-80 mg/day). The drug produced an average decrease of 28% and 34% in the plasma concentrations of total and LDL cholesterol. Serum cortisol levels showed similar increases in response to ACTH stimulation before and during mevinolin treatment, and the rates of excretion of urine-free cortisol were also similar. We conclude that clinically effective doses of mevinolin do not affect corticosteroid production by the adrenal cortex during prolonged ACTH stimulation in patients with heterozygous familial hypercholesterolemia.

Journal ArticleDOI
TL;DR: The existence of LHRH binding protein in adrenal cortical tissue with a molecular size similar to that of the pituitary receptor is demonstrated and the ligand-immunoblotting technique is applied.
Abstract: A new technique for the identification of LHRH receptors has been developed and applied to demonstrate an adrenal LHRH binding protein. Solubilized membrane proteins were separated electrophoretically and transferred to nitrocellulose paper. This was followed by sequential incubations with LHRH, anti-LHRH antiserum, peroxidase-conjugated second antibody, and 4-chloro-l-naphthol. Using an antiserum directed towards the middle region of LHRH, a 60K mol wt band was visualized in rat adrenal and pituitary membranes. A band of slightly higher molecular weight was present in membranes of bovine adrenal cortex but was absent in the medulla. The 60K band was not visualized when nonimmune rabbit serum was used. The 60K band was also not visualized when an antiserum requiring the NH2 and COOH termini of LHRH was used, suggesting that these regions of LHRH are not accessible to the antiserum after binding to the receptor. These studies have demonstrated the existence of LHRH binding protein in adrenal cortical tissu...