Adrenal Cortical Extract Research Articles

EFFECTS OF THYROTROPIC HORMONE, GONADOTROPIC FACTOR, PITUITARY GROWTH SUBSTANCE AND INSULIN UPON THE PHOSPHATASE CONTENT OF RAT FEMURS1

IN previous reports it was shown that certain hormonal preparations when injected into albino rats apparently produced changes in the phosphatase content of the femurs (Williams and Watson, 1941) For example, repeated small doses of parathyroid extract caused a temporary increase of the phosphatase of the diaphyses without demonstrable alteration of this enzyme in the epiphyses. Large single doses of the extract caused an increase, followed by a decrease, of the phosphatase of the diaphyses while only a decrease in the epiphyses was noted. The injection of adrenal cortical extract was followed by a reduction of the phosphatase of both the diaphyses and the epiphyses, the effect being more marked in the latter. Desoxycorticosterone acetate exhibited a tendency to raise the phosphatase activity of the bones. The administration of progesterone, testosterone, estradiol, thymus extract and thyroxin was followed by increases of the phosphatase content of the femurs.

BENEFICIAL EFFECT OF ESTROGENS ON ALTITUDE TOLERANCE OF RATS

IT IS well known that exposure to atmospheric conditions producing anoxia causes enlargement of the adrenal cortex. That this process serves a useful compensatory function is indicated by observations recently made in this laboratory by Lewis, Davis, Thorn and Jones (unpublished data). In their experiments two doses of adrenal cortical extract were given to normal rats 12 hours and 2 hours, respectively, before exposure. These consisted of 0.5 cc. of a concentrate in sesame oil, representing 10 cc. of Kendall's aqueous adrenal cortical extract per cc, or 750 gm. of adrenal cortical tissue. As judged by survivals in single exposures this treatment produced an increase in the tolerance of rats towards atmospheric pressure so lowered as to cause anoxia. The beneficial effect was equivalent to an increase of altitude tolerance of about 2000 to 3000 feet. Since desoxycorticosterone did not exert this effect in identical experiments, it was considered probable that the benefit depends on the carbohydrate regula...

Efficacy of adrenal cortical extract and of paredrine in the prevention of experimental shock following venous occlusion of a limb: Shleser, I. H., and Asher, R.: Am. J. Physiol. 138: 1, 1942

Efficacy of adrenal cortical extract and of paredrine in the prevention of experimental shock following venous occlusion of a limb: Shleser, I. H., and Asher, R.: Am. J. Physiol. 138: 1, 1942

EFFECTS IN THE DOG OF INFUSION OF ADRENAL CORTICAL EXTRACT ON EXERCISE TOLERANCE, BLOOD CONSTITUENTS AND ADRENAL CORTEX1

THE ASTHENIA and susceptibility to fatigue manifest in adrenal insufficiency, and the relief afforded by administration of adrenal cortical extract, have led to the suggestion that cortical extract might increase exercise tolerance and postpone fatigue in the normal animal. In the normal rat, however, very large doses of cortical extract have been found to cause cortical atrophy (Ingle, Higgins and Kendall, 1938); this property was found peculiar to those components with an oxygen on Cn (Wells and Kendall, 1940), although Selye (1940) claims to have found desoxycorticosterone effective. The experiments described herewith were undertaken to determine whether repeated intravenous infusion of whole cortical extract in the normal dog would affect a) the exercise tolerance, b) thelevel-of blood constituents related to adrenal cortical activity, or c) the histologic structure and bulk of the adrenal cortex. METHODS Six dogs, weighing 16 to 30 pounds, were used for the study of exercise

Treatment of Circulatory Collapse of Experimental Venous Occlusion: Use of Adrenal Cortical Extract and Saline Solution

SummaryThe shocklike syndrome of circulatory collapse and prostration was induced in a series of 18 dogs by a regional venous occlusion. Treatment at the time of collapse, by infusion of ACE and physiological saline, resulted in a marked increase in survival time in 6. In a control group of 12, saline infusion alone prolonged survival time in 2. ACE alone in a series of 12 proved ineffective.

EFFECT OF ADRENAL CORTICAL COMPOUNDS ON EDEMA FORMATION OF FROGS' HIND LIMBS1

THE METHOD of Cartland and Kuisenga (1936) for the assay of adrenal cortical extract depends on the ability of the test material to maintain the life of adrenalectomizied rats; it requires the use of relatively large quantities of extract and a period of several weeks for each determination. A somewhat more rapid and sensitive method is that of Selye and Schenker (1938) which makes use of the changes in the acute response of adrenalectc miz;ed rats to temperature fluctuations. This procedure requires moderate quantities of the fluid to be tested and a period of 24 hours for its completion. In the course of perfusion studies on isolated frog's legs (Loewen-Tren- delenburg preparation) it was found that small concentrations of adrenal cortical extracts in the perfusate markedly affect the development of edema in the legs. The rate of the edema formation, measured by the successive changes in weight.

Effects of Prolactin and Cortical Hormones on Body Weight and Food Intake of Adrenalectomized Pigeons

SummaryAdrenalectomized young Carneau pigeons fed 1.75 g of a salt mixture daily showed an average period of survival of 9 days. Such pigeons eat little food and lose weight. Prolactin induced more than normal gains in body weight when adrenal insufficiency was not acute and restored food intake to a level almost equal to that of unoperated birds. Either adrenal cortical extract or desoxycorticosterone acetate maintained life in adrenalectomized pigeons. Daily doses of 2 mg of desoxycorticosterone acetate fully restored the rate of increase of body weight and the daily food consumption to levels characteristic of normal unoperated pigeons. A group of birds given high dosage of both prolactin and adrenal cortical extract showed more rapid gains in body weight and larger food intake than has ever been observed in normal unoperated pigeons of the age used here.

INFLUENCE OF ADRENAL PREPARATIONS ON FISH MELANOPHORES1

THERE HAS LONG been a need for a simple method for assaying adrenal cortical extracts. Santa and his associates (1) have reported that epinephrinfree adrenal cortical extracts, as well as desoxycorticosterone, cause contraction of the melanophores of the scales of the fish Cyprinus carpio. This contraction, because it was incomplete and slow, could be distinguished from that caused by epinephrin, which was complete and rapid. The specificity claimed would be an improvement over the time consuming, expensive methods now in use. Therefore, we have attempted to employ the technique on preparations which had been assayed by other methods. We failed to find in this method either a quantitative or qualitative test for adrenal cortical substances. The scales of various species of fish were tested in an effort to find one in which melanophore distribution and reaction were suitable.

Use of Adrenal Cortical Hormone in CI. welchii Infections in Guinea Pigs

Summary and ConclusionsUnder the conditions of this experiment, it would appear that the adrenal cortical hormone extract has a protective value in delaying death in experimental Cl. welchii infections in guinea pigs.

Some Metabolic Effects of Testosterone Implants

Thorn and harrop (1) have shown that the administration of testosterone to normal dogs is followed by a decreased excretion of sodium and water, an effect resembling that of adrenal cortical extract. Kochakian and Murlin (2) found the nitrogen content of urine in castrate dogs diminished after the injection of androgens, while Thorn and Engel (3) noted a decrease in urinary nitrogen in normal dogs given testosterone propionate. These reports represent but a few of the recorded observations on animals. More recently, Kenyon et al. (4) have shown that in normal men and women, and particularly in eunuchoids, the injection of testosterone propionate ‘produced a reduction in the urinary excretion of nitrogen, sodium, potassium and chloride.’ When the injections of testosterone were discontinued, the excretion rates returned to the pre-injection levels. Jones et al. (5) noted that the oral administration of methyl testosterone possessed ‘the property of causing nitrogen, electrolyte and water retention.’

Assay of Adrenals for Lactogenic Hormone.

SummaryTwo commercial adrenal cortical extracts, whole untreated rabbit adrenals, and isoelectric precipitates of beef, hog and rabbit adrenals were assayed for lactogenic hormone by the sensitive intradermal “micro” pigeon crop gland technic. None of the adrenal compounds were found to contain lactogen.

MAMMARY GLAND DEVELOPMENT WITH MAMMOGEN I IN THE CASTRATE AND THE HYPOPHYSECTOMIZED RAT1

IN 1936, REECE et al. (1) published the first experiments showing that the mammary glands of completely hypophysectomized animals did not respond to administration of ovarian hormones. Gomez and Turner (2) soon demonstrated that the anterior pituitary gland from pregnant animals or those pretreated with estrogen contained a factor which would cause mammary development in hypophysectomized or normal guinea pigs. It was also demonstrated that thyrotropic, adrenotropic, and lactogenic AP extracts or adrenal cortical extract plus estrogen were ineffective in hypophysectomized guinea pigs. The theory was then advanced by Gome? and Turner (3) that a previously unrecognized pituitary factor or factors were the direct agents of mammary growth. This complex was called mammogen. From earlier observations with ovarian hormones it appeared that there must be two mammogenic factors. The duct growth factor {mammogen I) was thought to be stimulated to increased secretion by estrogen alone and caused mammary duct growth.

CAPACITY OF RATS LIVER TO INACTIVATE DESOXYCORTICOSTERONE ACETATE

CERTAIN CRYSTALLINE ESTROGENS AND ANDROGENS (1–7) and t h e endogenous ovarian estrogens and testicular androgens of the rat (8–12) are inactivated by the liver. Such evidence is used to explain the fact that natural estrogens and androgens are relatively ineffective when administered by mouth. Kuizenga, Nelson and Cartland (13) found that 2, of the adrenal steroids, corticoster one and dehydrocorticosterone, as well as certain adrenal cortical extracts were just as effective orally as when given subcutaneously. This indicates that these adrenal substances, unlike the gonadal hormones, are not inactivated by the liver. Desoxycorticosterone acetate, on the contrary, was found to be much less effective orally than parenterally. By transplantation experiments in the rat, Eversole, Edelmann and Gaunt (14) have shown that the endogenous adrenal hormone or hormones necessary For maintenance of life are not inactivated by the liver.

Effect of Adrenal Cortical Extract, Desoxycorticosterone, and Added Potassium upon Electrolyte Balance in Normals and in Addison's Disease

The diagnostic methods for adrenal cortical insufficiency are not entirely satisfactory. A reliable one is not available for the diagnosis of mild insufficiencies and those for Addison's disease are not without hazard. The production of a crisis by a high potassium intake either alone or in combination with a low sodium intake is dangerous. The Wilder (1) method in which a high potassium and low sodium intake are administered for a shorter period is the safest procedure, yet crises continue to develop with this test. It was pointed out in a previous report (2) that patients with Addison's disease are more sensitive to added potassium during periods of sodium chloride depletion than following corection of this depletion. It was also emphasized that sodium chloride restriction can be tolerated for long periods provided the sodium chloride stores are not depleted and provided that the potassium intake is low. Such restriction, however, with the sodium chloride stores depleted may provoke a crisis. These haza...

BIOLOGICAL ASSAY OF ADRENAL CORTICAL ACTIVITY

DESPITE THE WIDE USE OF ADRENAL cortical extracts, both clinically and experimentally, no quantitative method for determining their activity has been generally accepted. Of the various procedures advocated (1–5) many are too laborious or require the use of so many animals to avoid the normal biological variation as to preclude their general use. The majority of the advocated procedures which are satisfactory from a technical standpoint are based on non-specific reactions easily vitiated and hence entirely unreliable as standard methods of procedure. Thus, the fact that certain steroids derived from adrenal cortical extracts cause sodium retention in the adrenalectomised animal has suggested that this reaction might be used as a method of assay. However, the fact that many steroids having no adrenal cortical activity exert a similar sodium-retaining effect would preclude the use of this reaction as a method of assay.

METABOLISM IN ORGANIC HYPERINSULINISM

In 1932 Britton and Silvette 1 demonstrated that the secretion of the adrenal cortex is involved in the metabolism of carbohydrate. The experiments of Long and Lukens in 1936, 2 indicating that severe pancreatic diabetes could be greatly ameliorated by bilateral adrenalectomy, stimulated further investigation of the role of the adrenal cortex in carbohydrate metabolism. Much information has since been obtained with respect to the physiologic processes involved and the specific fractions of the adrenal cortical secretion responsible for the effects produced. 3 Since 1937 evidence has been presented which indicates that adrenal cortical extracts are capable of raising the blood sugar of normal, starving, starving-hypophysectomized, partially depancreatized and depancreatized-adrenalectomized animals. 4 Further, it has been reported 5 that normal mice are rendered resistant to the hypoglycemic effects of insulin by the previous administration of adrenal cortical extracts. These observations, indicating an anti-insulin effect of such substances, suggested this investigation.

Influence of Traumatic Shock on Blood Sugar of Adrenalectomized Rats Treated with Adrenal Cortical Extract.

Influence of Traumatic Shock on Blood Sugar of Adrenalectomized Rats Treated with Adrenal Cortical Extract.

INFLUENCE OF HORMONES UPON PHOSPHATASE CONTENT OF RAT FEMURS I. EFFECTS OFADRENAL CORTICAL SUBSTANCES AND PARATHYROID EXTRACT1

AS AN ATTEMPT to explain the apparent salutary effects of adrenal cortical extract when administered therapeutically to persons with Paget's disease of the bone(1, 2, 3) and chronic arthritis (4), the experiments described below were undertaken. In addition to more or less pronounced clinical improvement, the treatment of patientswith these diseases by means of adrenal cortical extract has been found to be accompaniedby a reduction of the serum phosphatase activity. The latter effect might be explainable in several ways, e. g., inactivation of the catalytic properties of the enzyme in the organism as a result of the treatment, increased elimination of the phosphatase by way of theintestine, biliary tract or kidney, or decreased rate of its production or delivery to the blood stream. We have performed experiments which show that adrenal cortical extract does not modify the activity of bone phosphatase in vitro.

ROLE OF THE ADRENAL GLANDS IN SHOCK

There is considerable evidence to substantiate the postulate that the adrenal cortex acts as a protective mechanism against the development of many of the so-called states of shock. Adrenalectomy produces a state of shock. Normal health and vigor under ordinary conditions may be maintained in adrenalectomized dogs by injections of adrenal cortical extract. However, these dogs have circulatory collapse following any stimulus which puts a strain on the organism. 1 Certain investigators have called attention to the similarity of the signs and symptoms of adrenal insufficiency and those of secondary or traumatic shock and have suggested that the latter may be due to failure of adrenal cortical function.1 Selye and his co-workers 2 have reported that one of the tangible evidences of the organism's attempt to combat shock is found in their studies, which showed increased activity of the adrenal glands during recovery from shock. Weil and Browne 3 found

Inability of Desoxycorticosterone to Maintain Lactation.

SummaryThe necessity of adrenal cortical secretions for the support of lactation in rats was confirmed. Desoxycorticosterone acetate, unlike adrenal cortical extract, was of no benefit at all in correcting this deficiency, and may have further depressed lactation.†