Cortical Extract Research Articles

IN VITRO STIMULATION OF PITUITARY FOLLICLE-STIMULATING-HORMONE RELEASE BY HYPOTHALAMIC EXTRACT.

SummaryOpposite halves of each of 72 anterior pituitaries from female rats were cultured in separate dishes. At the end of the 3rd and 6th days, the medium was removed and fresh medium containing neutralized acid extract of rat hypothalamus was added to one-half of the culture dishes, and medium containing cerebral cortical extract was added to the remainder. Each pituitary equivalent was cultured with an equivalent of 4 hypothalami from ovariectomized rats. Brain extracts were not added during the first 3 days of culture. After termination of culture, the medium was assayed for FSH by the method of Steelman and Pohley. Pituitary tissue cultured with cerebral cortical extract (control) did not release significant amounts of FSH, whereas pituitary cultured with hypothalamic extract (experimental) released highly significant amounts of FSH (average ovarian weights were 99 ± 7 and 149 ± 10 mg/100 g body weight, respectively). Control pituitary released significant amounts of FSH into the medium only during t...

A HYPOTHALAMIC FOLLICLE STIMULATING HORMONE-RELEASING FACTOR.

FSH activity in 1.5 ml of rat plasma was evaluated by a new sensitive mouse uterine weight method devised by the authors. No FSH activity was found in 1.5 ml of plasma from normal females, but it was readily determined in 1.5 ml plasma from chronically ovariectomized female rats. Treatment of ovariectomized females with single, subcutaneous doses of 50 ∧g estradiol benzoate and 25 mg progesterone significantly lowered plasma FSH activity on measurement 3 days later. Ten min after the intravenous injection of a crude acidic extract of 2 rat stalk-median eminences, a significant elevation in plasma FSH occurred in the ovariectomized, estrogen, progesterone-blocked rats, whereas cerebral cortical extract was without effect on plasma FSH in these animals. Furthermore, stalkmedian eminence extract failed to alter plasma FSH in hypophysectomized rats. The extract was also ineffective when injected directly into the immature test mice for 3 days. These results indicate that contamination of the extracts with FSH...

Effect of Steroids on Experimental Cerebral Infarction

Adrenal steroids have been used to treat cerebral edema ever since Prados et al 1 observed that spraying the cerebral cortex with adrenal cortical extract minimized the trypan blue staining which exposure otherwise induced. Pretreatment with cortisone also prevents edema formation around cerebral stab wounds, 2 and corticosteroids appear to reduce the edema that surrounds human and experimental brain tumors. 3,4 Whether corticosteroids reduce the cerebral edema and improve the clinical course of patients with ischemic cerebral infarction is unknown. Clinical statements have been made both pro 5,6 and con, 7 but there have been no controlled experimental studies on the problem. In the present work the glucocorticoid, dexamethasone, was given to rats both before and after a controlled anoxic-ischemic insult. The mortality and tissue changes were compared in treated and untreated animals. Method Adult male Sprague-Dawley white rats weighing 325-425 gm were used. As described in the previous paper

A HIGHLY SENSITIVE TEST FOR LH-RELEASING ACTIVITY: THE OVARIECTOMIZED, ESTROGEN PROGESTERONE-BLOCKED RAT.

The LH-releasing effect of crude acidic extracts of rat stalk-median eminence tissue was evaluated in chronically ovariectomized rats in which LH secretion had been partially blocked by injection of estrogen and progesterone. Ten min after intravenous administration of these extracts a significant increment in plasma LH was detectable, as measured by the ovarian ascorbic acid depletion test. The minimal effective dose (MED) of stalk-median eminence extract was approximately 40 μg wet weight of tissue extracted. By contrast, cerebral cortical extract was completely inactive at doses up to 5,000 μg wet weight of tissue extracted. Pitressin was active in inducing LH release in this test at doses of 200 or more mU. Thus, the quantity of Pitressin required to produce a positive response is approximately 200–400 times greater than the quantity of vasopressin found in the MED of hypothalamic extract. The MED for epinephrine was 5 μg, a quantity several thousand times the amount present in the MED of stalk-median...

Potassium excretion during adrenal insufficiency.

IT was first noticed by Harrison and Darrow1 that in adrenal insufficiency in dogs the renal tubular function of preserving sodium and excreting potassium was disturbed. This was afterwards interpreted generally as the result of insufficiency of the sodium-potassium exchange mechanism, which was advocated by Berliner et al.2 originally for the explanation of the high output of potassium under a special condition of extremely high potassium load. That the abnormality of excretion of potassium in adrenal insufficiency, except in the final stage, was not dependent upon changes in the glomerular filtration rate has been stressed by Harrison and Darrow1. However, their experiments were done under special conditions by giving potassium chloride (10 g) to the intact dog or the adrenalectomized dog treated with cortical extract in order to compare their concentration ratio (urine/plasma ratio) of potassium with that of the untreated adrenalectomized dog at the same high serum potassium-level found in the latter. The ratio obtained in the former reached 40–75, whereas that found in the latter was about 10. In our experiences the former values seem to be abnormally high, perhaps due to adaptation to potassium load2 to which no attention was paid, while the latter lies rather in the normal range. On the other hand, Harrop et al.3 and recently Fukuda and Koyama4 have noticed that the rise of concentration of potassium in the plasma in adrenal insufficiency paralleled that of urea or non-protein nitrogen and suggested the possibility that the disturbance in excretion of potassium might be the result of reduced glomerular nitration rate. Therefore, experiments were performed to find out whether the clearance of potassium shows direct relation to the glomerular filtration rate in adrenal insufficiency in dogs. The results were compared with those obtained from intact dogs and adrenalectomized dogs maintained with cortisone (1 mg/kg per day) when the glomerular filtration rate was changed by altering the intake of sodium chloride (0–2.0 g/kg per day).

Whole body x-irradiation, nitrogen excretion and the adrenal gland.

Urinary nitrogen excretion by the rat increases after whole body x-irradiation. This response to irradiation is suppressed by adrenalectomy and can be restored by treatment of the x-irradiated adrenalectomized rats with adrenal cortical extract. The weights of the thymus and the spleen are decreased and the weight of the liver is increased in the rat following whole body x-irradiation; adrenalectomy produces only quantitative changes in these responses without affecting the direction of the changes. Blood amino acid levels are not affected appreciably by x-irradiation. From these facts it appears that nitrogenous materials other than amino acids or simple polypeptides are transferred from certain body tissues to the liver after irradiation. In the normal irradiated animal these nitrogenous materials are converted in the liver to glycogen, and the excess nitrogen appears in the urine. In the adrenalectomized irradiated animal the liver is unable to carry out this conversion. Treatment of the adrenalectomiz...

Characterization of a calf hypothalamic extract with adrenocorticotropin-releasing properties: evidence for a central nervous system site for corticosteroid inhibition of adrenocorticotropin release.

ACTH secretion, as indicated by increments in plasma corticosterone concentration or by adrenal ascorbic acid depletion, was studied in rats. Histamino, laparotomy, serotonin, pitressin, synthetic arginine vasopressin, calf cerebral cortical extract, or calf hypothalamic extract was used as ACTH-releasing stimuli. Morphine inhibited ACTH release following all the stimuli except the hypothalamic extract. The extract was found to be free of significant ACTH contamination in assays of hypophysectomized rats. It is concluded that morphine does not impair ACTH release at the pituitary, and that the hypothalamic extract possesses a unique ACTH-releasing activity. Corticosterone, in amounts shown to be physiological, inhibited the secretion of ACTH following histamine or laparotomy, but did not affect the secretion of ACTH when it was provoked by pitressin or hypothalamic extract. The corticosteroid inhibition of ACTH release following histamine or laparotomy thus appears to occur in the central nervous system, and not in the anterior pituitary. A schema describing the functional localization of the various sites of action of stimulators and inhibitors of ACTH release based on these data is presented. Requirements for an in vivo assay of hypophysiotropic, ACTH-releasing neurohormones are summarized.

THE ACUTE EFFECTS OF INFUSED ADRENAL STEROIDS ON RENAL FUNCTION IN ADRENALECTOMIZED DOGS

ABSTRACT Infusions of cortisol (11β,17,21-trihydroxy-pregn-4-ene-3,20-dione), prednisolone (11β,17,21-trihydroxy-pregna-1,4-diene-3,20-dione), aldosterone (11β,21-dihydroxy-3,20-dione-pregn-4-en-18-al), and adrenal cortical extract have been given to four adrenalectomized dogs. The changes of inulin, creatinine, para-aminohippuric acid clearances, urine volume, and sodium and potassium excretion have been measured. Between experiments oral replacement therapy was given to obviate the effect of slow absorption of previously injected steroids. The effects of steroid-free control infusions have been studied. Varying the rate of infusion from 1.0–2.6 ml/min, and sodium from 0–170 μeq/min has little effect on glomerular filtration rates (G. F. R.). Infusions of cortisol (1.5 and 10 mg/h), prednisolone (2 mg/h) and adrenal cortical extract (10 ml/h) raised the G. F. R. and lowered the filtration fraction. As the G. F. R. increased the ratio creatinine: inulin clearance fell. The different dogs varied in their responses. Infusions of prednisolone and cortisol (1.5 mg/h) usually increased sodium output as G. F. R. rose. With aldosterone, adrenal cortical extract and cortisol (10 mg/h) there was sodium retention in three of the four dogs, the fourth was resistant to the sodium retaining action of these steroids while the plasma level was high. All steroid infusions increased potassium excretion. Cortisol increased free water clearance independent of G. F. R. provided the infusion rate exceeded 2 ml/min, prednisolone increased both osmolar and free water clearance, aldosterone increased osmolar clearance and reduced free water clearance.

Effects of thyroid and adrenal cortical hormones on restoration of liver protein and enzyme activity after partial hepatectomy in rats.

Propylthiouracil depressed and thyroxine elevated the succinoxidase activity of rat liver after 4 days of regeneration. Protein-depleted animals had a significant decrease in activity of succinic dehydrogenase and cytochrome oxidase, rate of restoration of liver mass, enzyme activity and new protein. Thyroxine increased the rate of regeneration and the enzyme activity even in protein-depleted animals. Adrenalectomized rats on low protein intake had a very low rate of regeneration and protein replacement and low amounts of new enzyme activity and new protein after partial hepatectomy. Increasing the dietary protein to 36% increased all of these factors significantly, but administration of cortisone or adrenal cortical extract, had little effect on enzyme activity even though its effect on protein restoration was about as good as that of the high protein intake. Apparently under certain conditions, these hormones can produce changes in specific enzyme proteins that are independent of changes in total cell protein.

The Effect of Cortisone Acetate on the Leukocytes of Young Chickens

ABSTRACT IT IS known that the adrenocorticotropic hormone (ACTH) and several adrenal steroids will decrease the number of circulating lymphocytes and eosinophils in certain mammals, Dougherty and White (1944) and Dougherty and Dougherty (1953). Less is known about the effects of ACTH and adrenal steroids on the circulating white cells in the chicken. Adrenocorticotrophic hormone has been reported by Huble (1955) to decrease lymphocytes and increase the number of heterophils, and to have no effect on lymphocytes and eosinophils, Stamler et al. (1950). Shapiro and Schechtman (1949) reported that the injection of adrenal cortical extract into adult chickens produced a transient lymphopenia and an increase in heterophils. The data of Huble (1955) and Bannister (1951) indicate that daily administration of cortisone acetate will reduce the lymphocytes and eosinophils and increase the number of heterophils in the chicken. The number of leukocytes and variation in differential counts after cortisone injection may not . . .

Influence of cortisone on the basophil granulocytes and the total white cell count in rabbit blood.

Several investigators (Ehrich, 1953; Asboe-Hansen & Kaalund-Jørgensen, 1956: and Boseila, 1958) have suggested that the basophil leucocyte and the tissue mast cell have some functional relationship in addition to their morphological similarities. Systemic cortisone administration results in a reduction of the number of the tissue mast cells, as well as degranulation or conglomeration of their granules (Asboe-Hansen, 1950; 1952; Videbæk et al., 1950); and oral cortisone administration induces a fall in the absolute count of circulating basophil leucocytes in man (Code et al., 1954). Injected subcutaneously, cortisone brings about a marked decrease in the total leucocyte count in rats (Hamilton, 1957). A single injection of adrenal cortical extract, corticosterone or cortisol produced lymphopenia in rabbits within few hours (Dougherty & White, 1944). In rabbits, as in rats, the lymphocyte is the predominant circulating white cell, and hence a total leucopenia might be expected along with the lymphopenia. The present investigation

Effect of x-ray irradiation on muscle fatigue in rats.

With the Ingle fatigue test, it has been demonstrated that a loss of muscle responsiveness, increased fatigability and decreased work output follow acute whole body irradiation. These effects increase with time postirradiation. In both normal and irradiated animals, strain differences were observed. In the dosage used, the administration of adrenal cortical extract did not improve performance. Adrenalectomy plus cortical extract did not improve performance. It has been postulated that the poor performance of the irradiated animals is related to a lack of glycogenolysis, poor intestinal absorption of glucose and circulatory collapse.

An experimental study of postoperative tumor metastases. II. Effects of anesthesia, operation, and cortisone administration on growth of pulmonary metastases.

CancerVolume 11, Issue 3 p. 460-462 ArticleFree Access An experimental study of postoperative tumor metastases. II. Effects of anesthesia, operation, and cortisone administration on growth of pulmonary metastases William E. Schatten M.D., William E. Schatten M.D. Surgery Branch of the National Cancer Institute, of the National Institutes of Health, Public Health Service, Bethesda, Md.Search for more papers by this authorWilliam M. Kramer M.D., William M. Kramer M.D. Surgery Branch of the National Cancer Institute, of the National Institutes of Health, Public Health Service, Bethesda, Md.Search for more papers by this author William E. Schatten M.D., William E. Schatten M.D. Surgery Branch of the National Cancer Institute, of the National Institutes of Health, Public Health Service, Bethesda, Md.Search for more papers by this authorWilliam M. Kramer M.D., William M. Kramer M.D. Surgery Branch of the National Cancer Institute, of the National Institutes of Health, Public Health Service, Bethesda, Md.Search for more papers by this author First published: May/June 1958 https://doi.org/10.1002/1097-0142(195805/06)11:3<460::AID-CNCR2820110304>3.0.CO;2-ECitations: 28AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. References 1 Agosin, M.; Christen, R.; Badinez, O.; Gasic, G.; Neghme, A.; Pizarro, O., and Jarpa, A.: Cortisoneinduced metastases of adenocarcinoma in mice. Proc. Soc. Exper. Biol. & Med. 80: 128– 131, 1952. 2 Baserga, R., and Shubik, P.: Action of cortisone on transplanted and induced tumors in mice. Cancer Research 14: 12– 16, 1954. 3 Baserga, R., and Shubik, P.: Action of cortisone on disseminated tumor cells after removal of primary growth. Science 121: 100– 101, 1955. 4 Diller, I. C.; Beck, L. V., and Blauch, B.: Effect of adrenal cortical extract on growth of certain mouse tumors. Cancer Research 8: 581– 589, 1948. 5 Eck, R. V.: Personal communication. 6 Engell, H. C.: Cancer cells in circulating blood; clinical study on occurrence of cancer cells in peripheral blood and in venous blood draining tumour area at operation. Acta chir. Scandinav. suppl. 201: 9– 70, 1955. 7 Fisher, E. R., and Turnbull, R. B. JR.,: Cytologic demonstration and significance of tumor cells in mesenteric venous blood in patients with colorectal carcinoma. Surg., Gynec. & Obst. 100: 102– 108, 1955. 8 Gaylord, H. R., and Simpson, B. T.: Effect of certain anesthetics and loss of blood upon growth of transplanted mouse cancer. J. Cancer Research 1: 379– 382, 1916. 9 Gottschalk, R. G., and Grollman, A.: Action of cortisone and ACTH on transplanted mouse tumors. Cancer Research 12: 651– 653, 1952. 10 Iwasaki, T.: Histological and experimental observations on destruction of tumour cells in blood vessels. J. Path. & Bact. 20: 85– 105, 1915. 11 Jude, J. R., and Schatten, W. E.: Effect of zymosan on heterotransplantation of tumors to rats. Cancer Research. In press. 12 Pomeroy, T. C.: Studies on mechanism of cortisone-induced metastases of transplantable mouse tumors. Cancer Research 14: 201– 204, 1954. 13 Pool, E. H., and Dunlop, G. R.: Cancer cells in blood stream. Am. J. Cancer 21: 99– 102, 1934. 14 Schatten, W. E.: Experimental study of postoperative tumor metastases; I, growth of pulmonary metastases following total removal of primary leg tumor. Cancer 11: 455– 459, 1958. 15 Snell, G. D.: Cytosieve permitting sterile preparation of suspensions of tumor cells for transplantation. J. Nat. Cancer Inst. 13: 1511– 1515, 1953. 16 Tadenuma, K., and Okonogi, S.: Experimentelle Untersuchungen über Metastasen bei Máusecarcinom. Ztschr. f. Krebsforsch. 21: 168– 172, 1924. 17 Warren, S., and Gates, O.: Fate of intravenously injected tumor cells. Am. J. Cancer 27: 485– 492, 1936. 18 Watanabe, S.: Metastasizability of tumor cells. Cancer 7: 215– 223, 1954. 19 Wood, J. S., JR.; Holyoke, E. D., and Yardley, J. H.: Experimental study of influence of adrenal steroids, growth hormone, and anticoagulants on pulmonary metastasis formation in mice. Proc. Am. A. Cancer Research 2: 157– 158, 1956. 20 Zeidman, I.; McCutcheon, M., and Coman, D. R.: Factors affecting number of tumor metastases; experiments with transplantable mouse tumor. Cancer Research 10: 357– 359, 1950. Citing Literature Volume11, Issue3May/June 1958Pages 460-462 ReferencesRelatedInformation

Pathologic changes in adrenalectomized and non-adrenalectomized rats exposed to cold.

Sexually mature male rats of the Sprague-Dawley strain were sensitized by removal of one kidney and feeding a diet containing 4 per cent sodium chloride. Adrenalectomized rats were treated with 4 cc. of aqueous adrenal cortical extract per rat per day. Groups of adrenalectomized and non-adrenalectomized rats were each subdivided into groups which were adapted to low temperature and kept at 3–5# for 60 days, and similar groups kept at room temperature forthe same period of time. An additional group of non-adrenalectomized sensitized rats were adapted to the overfeeding of the high salt diet by stomach tube. The amount of fluid diet represented approximately as much dry diet as was eaten ad libitum by the cold-exposed rats. The following pointswere established: 1. The rats exposed to cold ate much more food but gained less weight than did rats kept at room temperature. The rats which were overfed at room temperature became overweight.

LIVER GLYCOGEN DEPOSITION AFTER INTRAVENOUS AND INTRAGASTRIC ADMINISTRATION OF CORTISOL-4-C14TO RATS1

IN THE attempt to correlate the routes by which cortisol-4-C14 3 was administered with the types of radiometabolites excreted (1), the question arose as to the time required to elicit the biological response to the hormone. Furthermore, it was not known whether the corticoids triggered or participated in the reactions producing glycogen deposition in the liver. Winternitz and Long (2) reported that 2 injections of an adrenal cortical extract caused an increase in glycogen content in the livers of adrenalectomized animals in 2 to 4 hours. Ashmore and co-workers (3) showed that the subcutaneous injection of 17-hydroxycorticosterone appeared to increase the conversion of pyruvate to glucose in liver slices from adrenalectomized-diabetic rats within 2 hours and reached a maximum in 6 hours. Other investigators (1,4) have found that following intravenous or subcutaneous injection of radiocortisol approximately 85% of the C14 given was excreted in the bile in the first 4 hours in rats with biliary fistulas.

Work performance of rats following partial hypophysectomy.

HYPOPHYSECTOMY in the rat causes a profound muscular asthenia. In acute experiments work performance can be normalized by treatment with adrenal cortical extract (ACE) plus vasopressin (3). In the present report it is shown that removal of any part of the hypophysis causes an acute suppression of work which can be corrected by ACE only when the posterior lobe is present. For several weeks following posterior lobectomy the rats show subnormal work output which is not corrected by vasopressin. By six weeks following posterior lobectomy the work capacity of the rat has been spontaneously restored to a normal or nearly normal output. Male rats of the Sprague-Dawley strain were obtained from the Upjohn breeding colony and maintained on Archer Dog Pellets until they reached a weight of 200 ± 2 gm. In some experiments the rats were subjected to the stimulation of muscle immediately following operation and in others there was a recovery period of either 30 or 42 days prior to the work test.

Ion requirements for gastric acid secretion.

SummaryAcid secretion and O2 uptake measured in frog gastric mucosae in vitrooccur but at reduced rates when Na in bathing solutions is .6 mM or less. Both are raised towards maximal when Na is 10 mM. Secretion occurs at 75% maximal when Li replaces Na. Adrenal cortical extract reduces secretion with high Na and has no effect with low Na. Neither added Ca nor Mg is necessary for secretion, but secretion is reversibly inhibited by 1 mM ethylenediaminetetraacetate. Secretion occurs when K is .3 mM but is maximum at 3 mM. Secretion occurs at 20% maximal when Cl is .2 mM or less. Secretion is unaffected by replacing Cl by Br, but it is reduced when Cl is replaced by I.

MEDICAL MANAGEMENT OF ADRENALECTOMY AND HYPOPHYSECTOMY

Bilateral adrenalectomy or hypophysectomy will induce objective remissions in some patients with metastatic breast cancer. It is the purpose of this report to detail our methods for managing patients subjected to these procedures. These methods are based on clinical experience and physiological studies of over 200 patients submitted to either adrenalectomy or hypophysectomy. We shall attempt to describe the general medical management for both procedures and to suggest specific methods for handling the problems peculiar to patients with metastatic disease. Huggins and Scott, 1 in 1945, reported the initial experiences with bilateral adrenalectomy in four patients with advanced prostatic cancer. With the use of desoxycorticosterone and adrenal cortical extract they were unable to maintain life in their patients, although one patient survived almost four months. Subsequently, Green and co-workers 2 successfully managed adrenalectomy in a diabetic patient with the use of large amounts of adrenal cortical extracts. With the availability

Adrenal cortical activity in gastric carcinoma. I. Studies of plasma 17-hydroxycorticosteroid levels.

Adrenal cortical function in gastric cancer has been the subject of previous investigations. Dobriner and co-workers, 1 noting the presence of the abnormal steroid metabolite 11-oxyetiocholanolone on paper chromatography of urinary extracts in gastric cancer patients, postulated a disordered function of the adrenal cortex. This abnormal steroid metabolite was also present in patients with Cushing's disease. 2 Young and co-workers, 3 studying glucose metabolism in patients with gastric carcinoma, observed that supplementary adrenal cortical extract was necessary to produce normal hepatic glycogen deposition in patients who were receiving oral glucose feedings. Homburger and co-workers 4 have reported a disturbed water and electrolyte balance in gastric cancer patients, simulating in some respects that seen in adrenal hypofunction. Rhoads 5 applied the Kepler and the Cutler-Power-Wilder tests to two patients with gastric cancer in order to investigate the connection, if any, between neoplasm of the stomach and adrenal hormonal imbalance. The results

Anaphylactic shock in the mouse vaccinated with hemophilus pertussis: IV. Studies on the adrenal gland

1. 1. Hemophilus pertussis organisms have the ability of enhancing sensitization in the adrenalectomized mouse maintained on adrenal cortical extract. 2. 2. The mechanism by which sensitization is enhanced does not seem to be a result of the direct toxic effect of the organisms on the adrenal gland. 3. 3. The amount of 17-ketosteroids excreted in the urine is not altered by inoculating the animal with H. pertussis. 4. 4. Histopathologic studies fail to reveal any changes in the cellular structure of the adrenal gland following inoculation.