Adrenal Cortical Extract Research Articles

Blood levels of 17-hydroxycorticosteroids following the administration of adrenal steroids and their relation to levels of circulating leukocytes.

occurrence of neutrophilia and lymphopenia following the administration of ACTH or adrenal cortical extracts to mice. In 1948 these findings were confirmed in man by Hills, Forsham and Finch (2), who noted, in addition, a pronounced fall in eosinophils. These changes in the blood have been used widely as an index of adrenal cortical activity. With the development of a method for the determination of 17-hydroxycorticosteroids in small quantities of blood or plasma (3) it has become possible to determine the relationship of the changes in blood steroid levels to the changes in leukocytes. In order to investigate this relationship, standard doses of various corticosteroids were administered to normal individuals and the alterations in blood 17-hydroxycorticosteroids and in leukocytes were observed at intervals thereafter.

The Influence of Adrenal Cortical Extract on Immunological Phenomena In Vivo

Summary and Conclusions The data presented indicate a lack of effect of aqueous adrenal cortical extract on the union of antigen and antibody in the circulating blood of the rabbit. Despite the previous injection of this extract the injection of antigen into immunized animals resulted in a marked drop of complement, granulocytes, and circulating antibody. From these results and those of other studies it appears that the effects of these hormones on allergic reactions are due not to interference with the in vivo union of antigen and antibody, but probably are connected with their effects on the reactivity of mesenchymal tissues. Occasionally the mere handling and bleeding, or injection of saline, “aqueous alcohol,” or adrenal cortical extract into normal rabbits produced a lymphopenia and sharp decrease in serum complement. The mechanism of this effect is unknown.

Excretion of formaldehydegenic (FG) substances by normal and scorbutic guinea pigs.

Although several publications have suggested that ascorbic acid may be important in the function of the adrenal cortex (Long 1947, Sayers 1950) the role of ascorbic acid in the metabolic processes of the adrenal gland is still undetermined, and some of the evidence appears contradictory. Giroud et al. (1939, 1940, 1940a, 1941) have reported that normal adrenal function was dependent upon an adequate ascorbic acid supply. Supporting evidence for the presence of functional impairment of the adrenal cortex in scurvy may be seen in reports (Lockwood et al., 1933, 1936; Ratsimamanga, 1944) that adrenal cortical extracts favorably altered the course of scurvy in guinea pigs. Recent work has shown that the life of guinea pigs maintained on a diet deficient in ascorbic acid may be prolonged if the animals are given cortisone (Hyman et al., 1950; Schaffenburg et al., 1950).

Saline hydration and diuresis after adrenalectomy.

ANIMALS in adrenal insufficiency, when hydrated orally with water, cannot excrete the water at a normal rate. A delay in excretion is also obtained when the water is administered as glucose or 0.85% saline solution (Gaunt, 1944; Hays and Mathieson, 1945; Reforzo-Membrives, Power and Kepler, 1945). Even the administration of desoxycorticosterone acetate (DCA) or adrenal cortical extracts will only maintain a normal response to hydration for a short period of time (Gaunt, 1944; Gaunt, Liling and Cordsen, 1945; Hays and Mathieson, 1945), although injections of epinephrine will increase the diuresis. The adrenalectomized animal, receiving excess fluids, will also easily develop the syndrome of water intoxication. Adrenal steroids, particularly DCA, will offer good protection against water intoxication, without, however, markedly increasing urine output. Various theories have been elaborated in attempts to explain the failure of adrenalectomized animals to excrete water, glucose solution or 0.85% saline at a n...

Effects of ACTH, cortisone and adrenal cortical extract on carbohydrate metabolism of hypophysectomized dogs.

Summary and ConclusionsProlonged administration of ACTH and cortisone diminished and eventually abolished the insulin hypersensitivity of the hypophysectomized dog. Concomitant with these effects, ...

The dose response in man to oral and injected lipo-adrenal cortical extract.

THE oral administration of adrenal cortical extract (ACE) was reported by Osier in a case of Addison's disease over fifty years ago (1). A comparison of the effectiveness in Addison's disease of a glycerol extract of adrenals, given orally and injected as reported by Thorn et al. (2), indicated that two and a half times the parenteral amount of hormone was needed orally for equal effect. However, Conn and Silverman (3) showed that the oral requirement was one half of that needed for injection. In both of these publications there were reported physiologic changes such as the increase in potassium output and the retention of sodium, attesting to the effectiveness of the orally administered hormone. Metabolic changes also have been reported by Freeman and his colleagues at the Worcester State Hospital (4, 5) when extract of the adrenal cortex was given orally to schizophrenic patients. Decrease in lymphocytes was observed, together with alteration in the urine output as well as changes in the specific gravit...

Pituitary-adrenal cortical antagonism to estrogenic stimulation of the uterus of the ovariectomized rat; observations on structural specificity of crystalline steroids.

IT WAS demonstrated in an earlier report (Szego and Roberts, 1948) that adrenal cortical hyperactivity, induced by adrenocorticotrophin, had a powerful inhibitory influence on the responsiveness of the castrate uterus to administered estrogen. Attempts to reproduce a similar degree of depression with adrenal cortical extract or with certain pure crystalline steroids which were available at that time met with but partial success. The striking inhibition exerted by adrenocorticotrophin was not duplicated by any of the following: Compound A, testosterone, Up John’s adrenal cortical extract in oil, progesterone, or desoxycorticosterone acetate. The latter two steroids appeared to interfere to some extent with the uterine response to estrogen. However, the degree of inhibition was far short of the virtual obliteration of the response observed with endogenous adrenal cortical hyperactivity induced by adrenocorticotrophin. In an extension of these observations, it has been possible to demonstrate, as described i...

An effect of adrenalectomy and cortisone on tissue permeability in vitro.

A FEW years ago a simple technique was described whereby the swelling of tissue slices in various solutions could be measured1. This swelling was presumably largely the result of osmotic activity and reflected the permeability of structures within the tissue slice to substances in the bathing solution. With brain cortex slices it was found that some swelling occurred in isotonic or hypertonic sodium chloride solutions lacking protein. In solutions containing only sugars, extreme swelling occurred as if the sugars penetrated membranes freely and exerted no osmotic pressure. But in the presence of small amounts of electrolytes the sugars behaved as completely non-penetrating. The effects of various materials, including an adrenal cortical extract, were tested to see whether they could influence the swelling or the effect of electrolyte. No obvious result was obtained at that time. Clearly significant effects of adrenalectomy and cortisone, but not of deoxycorticosterone, have now been obtained.

ADRENAL CORTICAL FUNCTION IN HYPERTENSION

THERE is an impressive body of suggestive evidence for the importance of the adrenal cortex in various types of hypertension. The subject has been comprehensively reviewed by Sapeika (1) and Perera(2). In the present communication, some of the relevant clinical and experimental observations will be briefly recapitulated in order to place this investigation in its proper perspective. Pressor effects of desoxycorticosterone esters have been demonstrated in various animals (3, 4), and morphologic changes were first described by Selye et al. (5). These included generalized vascular lesions similar to those seen in human nephrosclerosis and in malignant hypertension. Subsequently, studies by Knowlton et al. (6), employing much lower dosages in rats, revealed no significant vascular lesions; but in nephritic rats (the nephritis being induced by cytotoxic serum) striking hypertension was readily induced. The development of these lesions can be inhibited by simultaneous administration of glucocorticoids or ACTH (7, 8). Loeb et al. (9) first reported hypertension in 2 patients suffering from Addison's disease, who were treated with desoxycorticosterone esters. This pressor effect has also been demonstrated in uncomplicated hypertensive vascular disease, but not in normotensive subjects (10). The elevation was masked by salt withdrawal and apparently blocked by simultaneous administration of adrenal cortical extract (11). Cortisone in a dose of 200 mg. per day was found to cause a small but definite depression of the blood pressure in a patient with hypertensive vascular disease, which persisted for several weeks after cortisone had been discontinued (12).

A quantitative method for the bioassay of the effect of adrenal cortical steroids on mineral metabolism.

The importance of the adrenal cortex in the regulation of mineral metabolism has been recognized since 1932, and much work has been carried out on the disturbances which result after adrenalectomy and the restoration to normal conditions following therapy with adrenal cortical extracts (Bauman & Kurland 1927, Loeb 1932, see also reviews by Gaunt 1949, Kendal 1948 and Noble 1950). Despite this, no bioassay method based on the direct measurement of this effect, has been developed to date comparable as regards accuracy and sensitivity with the liver glycogen test for the action of substances on carbohydrate metabolism (Venning 1946, Dorfman 1946 and Eggleston 1946). Mineral activity may be assessed by measuring the alteration of sodium and potassium levels either in plasma (Hartman & Spoor 1940, Wirz 1950) or urine (Harrop 1936, Thorn et al. 1938). Both these measurements are subject to wide variation arising from alterations in external factors such as diet,

A case of Waterhouse-Friderichsen syndrome with recovery following the use of cortisone, aqueous adrenal cortical extract and chemotherapy.

A case of Waterhouse-Friderichsen syndrome with recovery following the use of cortisone, aqueous adrenal cortical extract and chemotherapy.

Relationship between the adrenal cortex and radiation sickness; a review of the literature and a presentation of new data.

It has long been theorized that the adrenal gland is associated in some way with radiation sickness (4, 7, 10, 12, 19, 25, 27, 33, 34) or with some of the effects of radiation (15, 16, 19, 23, 25). In the earlier years, the adrenal medulla was studied extensively as a possible source of information (7, 19, 23); more recently attention has shifted to the adrenal cortex (4, 12, 15, 16, 25, 27, 33, 34), which as early as 1922 was suggested as a potential factor by Hirsch (10) and others. The theories on the relationship of the adrenal to radiation effects have been based on highly suggestive clinical, morphologic and pharmacologic findings. When these are assimilated in the light of present knowledge, the evidence becomes even more provocative. Some of the earliest work was done by Hirsch, who used anterior pituitary extracts and adrenal cortical extracts to prevent radiation sickness with some success, but found that posterior pituitary extracts had no apparent effect. Desjardins (7) quoted Tsuzuki as showing in 1926 that in rabbits given a lethal dose of radiation there could be demonstrated at autopsy (1) reduction of the fat content in the adrenal cortex, (2) degeneration of medullary cells, and, after extreme doses, (3) atrophy of the medulla. The highly significant work of Leblond and Segal (16) demonstrated convincingly that heavy irradiation of lymphatic tissue, with adequate shielding of the rest of the body, will produce hypertrophy of the adrenal cortex and involution of distant lymphatic organs, while in adrenalectomized subjects such involution does not occur. Martin, Rogers and Fisher (19) quoted Arrillaza and Izzo as describing a case of Addison's disease in which the patient died five days after receiving a routine series of x-ray treatments to a carcinoma of the tonsil. Attributing this to a lack of adrenalin, they heavily irradiated the remaining adrenal gland of a dog from which one adrenal had been removed. The irradiation was carried out through an operative wound, allowing a close target-subject distance. The dog suffered no ill effects, and autopsy twenty-six days later showed complete destruction of the adrenal medulla with viable islands of cortex surrounded by bands of fibrous tissue. Warren (33) reported that leukopenia and loss of lipoid from the adrenal cortex were common findings in the victims of the atomic bombing. He could not be sure, however, that these morphologic findings were not the result of “alarm” stimuli other than irradiation. Weichert (34) noted the striking similarity between Addison's disease and severe irradiation sickness and theorized that the toxic products of protein breakdown in irradiation produce a relative adrenal cortical insufficiency. He observed improvement in his patients after administration of desoxycorticosterone. Craver (4), from observations on mice, postulated that the adrenal cortex was necessary in some way to repair the general tissue damage resulting from irradiation.

Antagonism of anethole and adrenal extract on glycogen formation in adrenalectomized rats

Anise oil, anethole, and several related compounds inhibit the deposition of glycogen in the livers of fasted, adrenalectomized rats by adrenal cortical extract. This effect is reversed by increased levels of adrenal extract. Anethole blocks the effect of adrenal cortical hormones in reducing insulin sensitivity of adrenalectomized rats. Adrenal hypertropy of unilaterally adrenalectomized rats is increased by anethole. It is postulated that these compounds compete for an active carbohydrate intermediate formed during glycogenesis. The possible role of β-glucuronidase is also pointed out.

Oxidation product of stilbestrol; effects upon the rat pituitary of a non-estrogenic oxidation product of diethylstilbestrol.

ON THE basis of various lines of evidence accumulated in the study of estrogen metabolism in women and in rodents, Smith and Smith (1941, 1946, 1948) have postulated that estrogenically inactive oxidation products of the estrogens, rather than estrogens per se, are directly responsible for the release of pituitary tropic factors. One line of evidence for this concept lay in the finding (Smith, 1944) that the presence of the testes or the simultaneous administration of progesterone to the castrate prevented the release of adrenotropic and gonadotropic factors from the pituitary following estrone administration to mature male rats. Progesterone, testosterone and adrenal cortical extract, in sufficient dosages, have been found to suppress the in vivo inactivation of the estrogens (see Smith, 1944, footnote 2, for references, and Segaloff, 1947). The observations in estrone treated rats, therefore, were interpreted as further support for the hypothesis that estrone increased the output of pituitary

Further observations on the role of the adrenal cortex in the metabolism of amino acids.

PREVIOUS data derived from the measurement of urea formation in nephrectomized rats have been interpreted to indicate that the adrenal cortex was not concerned in the catabolism of amino acids (Engel, Schiller and Pentz, 1949; Bondy, Engel and Farrar, 1949). Neither adrenal cortical extract nor previous adrenalectomy were found to have any measurable effect on the rate of urea formation during a 3–4 hour period following the intravenous administration of amino acids. Indeed, our results were interpreted as indicating that the intravenous administration of amino acids actually suppressed the catabolism of endogenous protein that occurred after administration of cortical extract. Bondy (1949) showed indisputably that adrenal extract had an effect on peripheral protein by demonstrating an increased accumulation of amino acids in the plasma of eviscerated rats treated with adrenal extract. This has been confirmed in cortisone-treated eviscerated rats (Ingle, 1950). Both the accelerated accumulation of amino acids

PLASMA ASCORBIC ACID AND PITUITARY-ADRENAL ACTIVITY

In a study of the relationship of ascorbic acid metabolism to pituitaryadrenal function in the rat, the effect of stress, adrenalectomy, hypophysectomy, and administration of an adrenal cortical extract on the plasma ascorbic acid concentration was determined. Surgical trauma and cold elicited a triphasic, and scalding a biphasic, response in both intact and adrenalectomized animals. The plasma ascorbic acid concentration decreased after adrenalectomy and hypophysectomy but returned to normal or above normal level following the administration of an adrenal cortical extract. It is suggested that the pituitary–adrenal system plays a facilitating role in the increased synthesis of ascorbic acid elicited by stress.

Further studies on mechanism of increased capillary permeability in inflammation with the aid of cortisone and ACTH.

Summary and ConclusionsCortisone fails to obliterate the spreading reaction caused by hyaluronidase. This substance seems to inhibit at times somewhat the increased capillary permeability induced by 500 to 900 γ of hyaluronidase. An alkaline exudate or leukotaxine induces an increase in the local capillary permeability. Thus, as shown (1,2), the materials are inhibited by adrenal cortical extract or by cortisone. When, however, the exudate is acid in reaction, the local increased capillary permeability is not repressed by either cortisone or by adrenal cortical extract. This is shown to be referable to another factor liberated in the later stages of an acute inflammatory reaction. This substance is concerned with the mechanism of increased capillary permeability in inflammation. This factor is termed “exudin.” Consequently the initial increase in capillary permeability in the development of inflammation is referable to leukotaxine. With the progress of the acute inflammation the pH of the exudate becomes ...

Recovery from prolonged cardiac arrest

1. 1. We have presented a brief review of the history of cardiac arrest and its management. 2. 2. A case is presented in which the heart was inactive for sixteen minutes. After manual massage it resumed its activity and the patient made a complete recovery. 3. 3. We believe that the anterior traristhoracic approach in such emergencies is the method of choice. 4. 4. Auxiliary measures, e.g., adrenal cortical extract, mechanical resuscitation and glutamic acid, were also used and are discussed. 5. 5. Glutamic acid therapy apparently aided mental and physical recovery which were definitely lessened when a placebo was substituted on two occasions.

Studies on the role of the adrenal in anaphylaxis and histamine-shock.

THE adrenal gland has been suspected of involvement in allergic conditions for over 20 years. In an early paper Wyman (1929) reported that adrenalectomized rats with adrenal transplants in the abdominal muscles were as susceptible to histamine poisoning and anaphylactic shock as adrenalectomized rats without transplants, but treatment with adrenalin somewhat alleviated this susceptibility. In a later paper, however, Wyman and Turn Suden (1937) reported the lethal doses of histamine to be as follows: normal rats, 100 mg. per kg. of body weight; adrenalec-tomized rats, 10 mg. per kg.; and adrenalectomized rats with adrenal transplants, 40 mg. per kg. Ingle (1937) also showed that autoplastic cortical transplants do not completely replace the function of the excised gland in rats. Perla and Gottesman (1931) found that adrenal cortical extract decreased the susceptibility of adrenalectomized rats to histamine and suggested that this property could serve as a basis for a cortical hormone assay.

Gastric secretion in the adrenalectomized rat.

TUERKISCHER and Wertheimer (1945) using a modification of the technique for the study of gastric secretion first reported by Roe and Dyer (1939) found a significant decrease in gastric secretion in adrenal-ectomized rats. They particularly emphasized the point that this decrease in gastric secretion could not be accounted for by the surgical trauma imposed upon the animal. A normal volume of secretion was obtained after bilateral adrenal-enucleation. The decrease in gastric secretion following adrenalectomy could be corrected with adrenal cortical extract but not with desoxycorticosterone acetate or normal saline. It seemed important to attempt to confirm these findings. The results herein reported extend and confirm those published elsewhere (Madden and Ramsburg, 1951).