Cortical Hormones Research Articles

Effect of irradiation to adrenal upon circulating adrenal medullarv hormone in the rat.

In a previous study (1), we described the effect of irradiation to the adrenal of the rat upon the level of blood corticosterone, especially after stimulation by ACTH injection. The irradiated animals showed a lower level of this adrenal cortical hormone than did the controls. This study has now been extended to the adrenal medullary hormones. While it is known that the adrenal medulla is relatively resistant to irradiation (2), at least as compared with the cortex, so far as we are aware, no experimental series has been followed with studies of these hormones after irradiation. Weil-Malherbe and Bone (3, 4) have described a method for measuring epinephrine-like substances in the blood, as well as a procedure for evaluating epinephrine and norepinephrine by means of differential filters and a suitable calculation. We planned to repeat, as closely as possible, the program of the earlier cortical study except that, since the amount of blood required entailed the sacrifice of the animal, only one measurement...

A COMPARISON OF FREE ADRENAL CORTICAL STEROIDS IN THE BLOOD OF A HIBERNATING AND NON-HIBERNATING MAMMAL

White rats and hamsters were fasted and exposed to cold (6 ± 1 °C) for various periods of time. The adrenal glands were weighed and adrenal cortical steroids were extracted from the blood for separation by paper chromatography.The adrenal weight was not a reliable index of adrenal cortical activity as measured by the quantities of circulating hormones. Two steroid fractions were separated from rat and hamster blood. The fast component was identified as corticosterone and the slow component as an amorphous fraction.The adrenal cortical response to cold is different in rats and hamsters. The hamster does not have the typical alarm reaction and only trace quantities of hormones are found in the hibernating animal. Within 6 hours of arousal the concentrations of circulating adrenal cortical hormones have increased to or beyond those of the control animals. The changes in circulating adrenal cortical hormones of hamsters exposed to cold for varying periods of time can be correlated with changes in their intermediary metabolism and ion balance.

The Effect of Cecal Coccidiosis Infections and Experimental Hemorrhage upon Adrenal Ascorbic Acid Levels in the Chicken

The role of the adrenals in resistance to parasitic infection in birds has been given little attention. This has been due in part to an incomplete understanding of avian adrenal physiology, and to a lack of appropriate methods for measuring changes in adrenal function. Many studies of mammalian species, and of the rat in particular, have employed the depletion of adrenal ascorbic acid as an indicator of response to stress (Long, 1947). Under certain conditions adrenal ascorbic acid depletion has been shown to be closely correlated with adrenocorticotropic hormone levels (Sayers, Sayers and Woodbury, 1948). The mechanism of ascorbic acid depletion and its relationship to the biosynthesis and secretion of adrenal cortical hormones, however, remains to be demonstrated.

A comparison of the growth suppressive effect of cortisone, prednisone, and other adrenal cortical hormones

Normal linear growth was noted in all of thirteen children given sufficient cortisone over a period of six months or longer to suppress asthma. Linear growth suppression was noted in twelve of thirteen children given prednisone, five of nine given methylprednisolone, the two given fluprednisolone, and in the one given triamcinolone, when sufficent corticosteroid was given for a similar period of time to produce the same degree of suppression of asthma. Evidence is presented indicating that cortisone is about one fifth as potent as prednisone and one sixth as potent as methylprednisolone as a therapeutic agent in asthma, but only one tenth as potent as each as a growth inhibiting agent.

Dynamic aspects of cholesterol metabolism in different areas of the aorta and other tissues in man and their relationship to atherosclerosis.

Tracer doses of cholesterol-4-C 14 were administered to each of 8 patients with limited life expectancies. Chemical determinations of free and esterified cholesterol and determinations of their C 14 -specific activities were made in serially collected sera, in tissues, and in the different layers of the abdominal aorta, the intimas of which were separated where possible, into normal-appearing intima, thickened intima, and free-lying lipid material. The turnover times of the free and esterified cholesterol fractions of the various tissues and the portions of those fractions derived from the plasma and by synthesis were calculated from these data. The plasma and liver free cholesterol fractions were in equilibrium at the earliest time, 2.5 days. The free cholesterol fractions of other tissues were in equilibrium with the plasma free cholesterol at later dates. The esterified cholesterol fractions of the various tissues, including liver, were in equilibrium with that of the plasma at later dates than were their free fractions. The findings indicate that a large portion of the cholesterol ester of the plasma is not derived from the liver. The greater part of both the free and ester cholesterols of other tissues was derived from the plasma, although a significant portion was derived by synthesis, except for both fractions of skeletal muscle. The adrenal glands were the most active in the synthesis of free cholesterol. The data indicate that a major portion of adrenal cortical hormones is synthesized directly from acetate, without cholesterol as an intermediary product. A major portion of the cholesterol of the intima was derived from plasma through interchange but a considerable amount of cholesterol was synthesized in the intima. The free-lying lipids in the intima appeared to be inert. Data concerning the changes of the lipid contents of the intima with the development of atherosclerosis have been presented. One patient, who died of a second myocardial infarction, differed from the others in having a longer turnover time of the cholesterol of his intima.

The role of aldosterone in man. Evidence for regulation of electrolyte balance and arterial pressure by a renal-adrenal system which may be involved in malignant hypertension.

FOLLOWING demonstration of the remarkable biological effects of hydrocortisone, many investigators were willing to recognize this steroid as the major and totipotent hormone secreted by the adrenal cortex. However, in 1950 it was found 1 that steroidal extracts of urine from patients forming edema contained a material which was potent in promoting sodium retention and potassium excretion in adrenalectomized rats. This finding was perhaps a stimulus to the important work which led to the isolation and characterization 2 of the adrenal cortical hormone aldosterone. Aldosterone is present in relatively minute amounts in plasma (one one-hundredth of the concentration of hydrocortisone), but its great potency indicates that it plays a major role in regulating the amount of sodium and potassium in the body; through its direct effect on the renal tubule it accelerates renal retention of sodium chloride and the elimination of potassium ions. In normal individuals aldosterone secretion may

RENAL AND EXTRARENAL ACTIONS OF ALDOSTERONE AND ITS INFLUENCE ON SODIUM TRANSPORT

Although there is general agreement that aldosterone (11β, 21-dihydroxy-3,20-dioxo-pregn-4-ene-18-al) is the sodium retaining hormone of the body, knowledge of its mechanism of action is, as with the other cortical hormones, fragmentary. This concerns not only the site of action in the kidney where it mediates its effects on sodium absorption but also the nature of the underlying mechanism by which these are brought about. Even more uncertainty and divergent opinion exist regarding its extrarenal activities, if any, a problem already investigated and discussed with the same intensity in the case of its predecessor deoxycorticosterone (21-hydroxy-pregn-4-ene-3,20-dione). In order to elucidate possible extrarenal actions of aldosterone, experiments on isolated organs were undertaken. Here on the isolated frog heart, no definite effect could be demonstrated up to concentrations of 10−4(g/ml), but at the same concentration, the spontaneous movements of the isolated rabbit intestine are diminished simultaneously with a decrease in tonus.

Antileukaemic activity of glycyrrhetinic acid.

RECENTLY some pharmacologically interesting activities of glycyrrhetinic acid corresponding to those observed with the adrenal cortical hormones have been shown; for example, a DOCA-like effect on sodium and potassium metabolism in normal people1 and an anti-inflammatory activity in different animal tests2.

Variations in hepatic inactivation of corticosterone with changes in food intake: an explanation of impaired corticosteroid metabolism following noxious stimuli.

In studies involving nine different noxious stimuli, all stimuli which diminished food intakes of male or female rats also diminished the capacity of the liver to inactivate adrenal cortical hormones by ring A reduction. All noxious stimuli which failed to affect food consumption also failed to affect corticosterone metabolism. In every case, the loss of hepatic capacity for inactivation of corticosterone following exposure to noxious stimuli could be duplicated exactly in control animals pair-fed to those exposed to the noxious stimuli. Hepatic Δ4-steroid hydrogenase activitjr was found to be a nearly linear function of food intake in the 18 hours immediately preceding the assay. Variations in water intake, and in ACTH or corticosterone secretion rate or concentration were not involved in the loss of hepatic Δ4-steroid hydrogenase activity following exposure to noxious stimuli. Three in vivo experiments demonstrated that variations in the rate of ring A reduction of adrenal cortical hormones bj' liver in...

Studies on Rat Adipose Tissue in Vitro: VII. EFFECTS OF ADRENAL CORTICAL HORMONES

Studies on Rat Adipose Tissue in Vitro: VII. EFFECTS OF ADRENAL CORTICAL HORMONES

Abrupt changes of water and sodium excretion in normal and adrenalectomized dogs

An experiment was designed to induce rapid changes in sodium and water excretion. With this procedure normal dogs showed a prompt and marked water diuresis, with an accompanying antinatriuresis. The same dogs, adrenalectomized and maintained on constant adrenal cortical hormone therapy, demonstrated an identical response despite the constancy of steroid concentration, suggesting a ‘permissive’ action of the hormones. When the animals were deprived of therapy for several days the excretion patterns of sodium and water did become markedly abnormal. Acute replacement with hydrocortisone restored the water excretion pattern to normal but did not correct the abnormal sodium excretion pattern. Aldosterone, given prior to and during the experiment, failed to restore either the water or sodium excretion patterns. The results obtained with acute replacement of hydrocortisone and aldosterone were identical with those obtained with hydrocortisone alone.

Correlated studies on plasma free corticosterone and on adrenal steroid formation rate in vitro.

ABSTRACT The effects of various stimuli on the rate of formation of adrenal cortical hormones in vitro and on the plasma free corticosterone were studied in rats. First, a simple method for the determination of corticosterone in rat plasma is described which is based on the fluorescence of this steroid in sulfuric acid. In contrast to procedures described by other workers the present technique does not require expensive spectro-fluorometers, but can be performed using a simple fluorometric unit consisting of components which are generally available. The results obtained with the two methods have shown that the steroid formation rate in vitro and the plasma free corticosterone increases after formalin stress, environmental change and injection of corticotrophin. Hypophysectomy leads to a marked and rapid decline of adrenal activity in vitro and of the plasma free corticosterone.

EXPERIMENTAL IMMUNOLOGIC ADRENAL INJURY

Twenty-three unilaterally adrenalectomized guinea pigs were injected with autologous and homologous adrenal tissue homogenates respectively, in Freund's adjuvant. Widespread adrenal lesions were found in 10 of 12 animals receiving auto-antigen and to a lesser extent in 6 of 11 animals injected with homologous pooled antigen. Widespread systemic lesions were present in both these and in control animals receiving Freund's adjuvant alone. These latter animals showed no adrenal involvement. The early changes within the adrenal consisted of perisinusoidal cellular proliferations in the deeper layers of the cortex. Focal granulomata developing at a later stage tended to become confluent and to displace cortical cells. Some loss of these cells was attributable to ischemic injury. The localization in the deep fasciculata and reticularis was thought to depend (a) on the varying antigenicity of adrenal cortical components, (b) the possible inhibitory effect of antiphlogistic adrenal cortical hormones on the development of lesions in the outer cortex, and (c) the presence of littoral cells in the deep cortex. These cells are thought to be involved in the mediation of the stimulus initiating differentiation of primitive mesenchymal cells in response to a circulating auto-antigen. The medullary lesions may be related to the presence of ectopic reticularis cells in this location. It was suggested that the cellular response in the target organ to injections of adrenal homogenates may denote a specific "organ-self" recognition mechanism involving an immune (i.e. defensive) reaction. It was postulated that this may be an accentuation of the physiological function of immunologically competent cells. Their proliferation, under normal circumstances, would prevent by means of production of "binding" globulins, the escape and dissemination of endogenous freed adrenal antigens into the circulation. Although the experimental stimulus arose from without the gland, by virtue of the presence of a circulating adjuvant-bound antigen, the adrenal reaction followed the same pattern as would obtain if the antigen was liberated within the suprarenal cortex.

Steroids. CXXXVII.1 Synthesis of a New Class of Potent Cortical Hormones. 6α,9α-Difluoro-16α-hydroxyprednisolone and its Acetonide

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSteroids. CXXXVII.1 Synthesis of a New Class of Potent Cortical Hormones. 6α,9α-Difluoro-16α-hydroxyprednisolone and its AcetonideJ. S. Mills, A. Bowers, Carl Djerassi, and H. J. RingoldCite this: J. Am. Chem. Soc. 1960, 82, 13, 3399–3404Publication Date (Print):July 1, 1960Publication History Published online1 May 2002Published inissue 1 July 1960https://doi.org/10.1021/ja01498a041RIGHTS & PERMISSIONSArticle Views261Altmetric-Citations57LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (789 KB) Get e-Alerts Get e-Alerts

Accumulation of Substrate by Isolated Rat Diaphragm: a Possible Mechanism for the Anti-Inflammatory Action of Corticosteroids

ADRENALECTOMY enhances, and adrenal cortical hormone depresses, the incorporation of carbon-14 from amino-acids, and from amino-acid precursors, into the protein of isolated rat diaphragm1,2. These changes are, at least in part, the result of a direct effect on protein biosynthesis1,3. Whether corticosteroids also effect protein synthesis indirectly by influencing amino-acid transport and accumulation is not known. The possibility was tested by measuring the penetration and accumulation of [1-14C-]-aminoisobutyric acid4, a non-utilizable amino-acid analogue, and of the utilizable amino-acids [U-14C] L-phenylalanine and [U-14C] L-lysine, by ‘intact’ diaphragms5 isolated from normal, adrenalectomized, and cortisone-treated rats.

Steroids. CXXXVI.1 Synthesis of a New Class of Potent Cortical Hormones. 6α-Fluoro- and 6α,9α-Difluoro-16α-methylprednisolone and Related Steroids2

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSteroids. CXXXVI.1 Synthesis of a New Class of Potent Cortical Hormones. 6α-Fluoro- and 6α,9α-Difluoro-16α-methylprednisolone and Related Steroids2J. A. Edwards, H. J. Ringold, and Carl DjerassiCite this: J. Am. Chem. Soc. 1960, 82, 9, 2318–2322Publication Date (Print):May 1, 1960Publication History Published online1 May 2002Published inissue 1 May 1960https://doi.org/10.1021/ja01494a054RIGHTS & PERMISSIONSArticle Views174Altmetric-Citations31LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (663 KB) Get e-Alerts Get e-Alerts

Oestrogen-insulin interaction on the uterus of the rat.

THE physiological activity of a specific hormone may be greatly modified by the presence or absence of other hormones, as evidenced, for example, by the Houssay effect1; the inhibitory action of adrenal cortical hormones on the response of the rat uterus to œstrogens2; the interaction of the various cestrogens on uterine growth3; the synergistic effect of growth hormone and thyroxine on body-growth in hypophysectomized animals4, etc. Of more immediate relevance to the subject to be treated here is the finding that the response of the mouse vagina to œstrogen is heightened by local application of insulin5; analogies between the effects of œstrogen and those of insulin on the mitotic activity of mouse ear epidermis have been pointed out by Bullough6. Other similarities between the generalized action of insulin and the specific effects of œstrogens on their target organs include an increased potassium uptake by the responding tissue7–9, and a heightening of glycogenesis and lipogenesis10–16. The foregoing observations, together with the fact that except in a few specific preparations œstrogens are ineffective in vitro 15, and in large doses produce a transient diabetes16, suggest a possible interaction between insulin and œstrogen.

Further studies on passive transfer of protection against lethality of endotoxin.

SummaryThe broad protection against lethality of endotoxin obtained by passive transfer from endotoxin-tolerant donors is not mediated by adrenal cortical hormone, properdin, or phagocytosis-promoting factor. Limited protection by normal donor serum given i.p. shortly before, but not simultaneously with, inoculation of endotoxin has been demonstrated. The results are not explained by direct inactivation of endotoxin by serum. Heating removes this activity from normal, but not completely from tolerant, donor serum.

Adrenal cortical hormone and incorporation of C14 from amino acid precursors into muscle protein.

The incorporation of C14 from labeled glucose, carboxylic acids and bicarbonate into the protein of isolated rat diaphragm was enhanced by adrenalectomy and decreased by cortisone treatment. The incorporation of radioactivity from pyruvate-3-C14 into the protein of diaphragms from adrenalectomized rats was not appreciably altered by a 20-fold change in pyruvate concentration. Incorporation of C14 from glucose-1-C14 and from glucose-6-C14 was the same, as was the magnitude of the increase after adrenalectomy.

Cytological Study Concerning the Effects of the Adrenal Cortical Hormone on the Secretory Activity of the Gastric Peptic Cells

In order to study the effects of the cortical hormone of the suprarenal glands on the secretory activity of the gastric peptic cells, hydrocortisone 1mg, 5mg, 10mg per 1kg of the animal's weight was injected subcutaneously 1 time, 5 times and 10 times and, on the other hand, hydrocortisone 10mg/kg or anthranilic acid 10mg/kg was injected for 5 days after the total extirpation of the suprarenal glands. The secretory activity of the gastric peptic cells in each experiment was compared and discussed with those obtained in case of normal animals. The results obtained can be summarized as follows.1. It is obvious that the cortical hormone has some effect upon the secretory ability of the gastric peptic cells. The fact can be analyzed as in the following cases.2. The regular and sure effect is to inhibit the discharge of the gastric hormone productin from the gastric surface cells, regardless of the dose injected. Accordingly, as a result of this effect, a small dose of the hormone seems to be inhibitory on the secretory activity of the peptic cells.3. A large dose of the hormone inhibits the secretory activity of the peptic cells more remarkably than it inhibits the discharge of productin.4. An intervening dose of the hormone has irregular effects in different cases, it sometimes actively promotes production of secretory granules in the peptic cells and sometimes vacuolization of the granules. The reason for this, it is assumed that the cortical hormone is not a direct stimulant of the secretory activity of the peptic cells but effective on it by the balance with some other substance.5. As a result of the extirpation of the suprarenal glands and of the injection of 10mg/kg hydrocortisone or 10mg/kg anthranilic acid for 5 days after the extirpation, it is noticed that a promotive effect on the vacuolization of the peptic secretory granules seems to be peculiar to the cortical hormone in addition to its regular and sure effect on productin secretion.