Corticosteroid Output Research Articles

Effect of corticotropin on activity of adrenal cortex of newborn boy.

It has long been observed that the adrenal cortex of the newborn child differs morphologically from that of the older child or the adult. With the advent of corticotropin (ACTH) and more precise analytical procedures, studies were initiated to determine whether the adrenal cortex of the newborn infant responds as actively to stress as does the older child or the adult. Klein and Hanson 1 reported less response to corticotropin in infants during the first week of life than in infants over a week old, as determined by the eosinophile response. However, Bergstrand and co-workers 2 have challanged the validity of the eosinophile measurements as evidence of adrenocortical activity. Read and co-workers 3 administered corticotropin to infants and determined adrenocortical activity by measuring the urinary output of 17-ketosteroids and corticosteroids. They observed a response to corticotropin in the newborn infant when sufficient hormone was injected. However, only 10 infants were

AN IN VITRO ASSAY OF CORTICOTROPHIN

The ability of corticotrophin to increase the corticoid output of rat adrenals in an isolated gland system has been developed as a useful assay method for the measurement of corticotrophin potency. The extra corticoids produced by stimulation are measured in terms of cortisone. Log dose response curves are presented for corticotrophin levels from 0.002 to 0.135 I.U./100 mgm. adrenals. A four point assay design, the precision of corticoid measurements, and the characteristics of the log dose response curves for a number of types of corticotrophin are given. With four measurements of each dose level the average lambda s/b for 20 assays was 0.209 ± 0.085 (S.D.).

AN IN VITRO ASSAY OF CORTICOTROPHIN

The ability of corticotrophin to increase the corticoid output of rat adrenals in an isolated gland system has been developed as a useful assay method for the measurement of corticotrophin potency. The extra corticoids produced by stimulation are measured in terms of cortisone. Log dose response curves are presented for corticotrophin levels from 0.002 to 0.135 I.U./100 mgm. adrenals. A four point assay design, the precision of corticoid measurements, and the characteristics of the log dose response curves for a number of types of corticotrophin are given. With four measurements of each dose level the average lambda s/b for 20 assays was 0.209 ± 0.085 (S.D.).

Studies of ACTH action upon perfused bovine adrenals; minimal ACTH concentration requisite for maximal glandular response.

introduction IN THE previous paper, the response of the venous cannulated-lacerated cow adrenal (V-L gland), perfused with citrated homologous blood to maximal concentrations of ACTH was described (Macchi and Hechter, 1954). In the present work, various concentrations of ACTH were perfused through isolated V-L cow adrenal glands. By comparing the corticosteroid output response of different glands perfused with a constant concentration of ACTH, it has been possible to obtain an estimate of the minimal ACTH concentration required to produce maximal rate of corticosteroid biosynthesis in this system. methods Cow adrenal glands (weighing between 15 and 27 gm.) were utilized in these studies. Venous cannulated-lacerated glands were perfused at a blood flow rate of 1 liter per hour, independent of gland weight, with homologous citrated blood at temperatures of 38° ± 1° C. The adrenal effluent was removed from the system, and was not permitted to recirculate through the gland.

Influence of sulfhydryl compounds on in vitro steroid production by the rat adrenal gland.

ALTHOUGH there have been numerous reports on the effects of adrenal-L ectomy, adrenocorticotropic hormone and cortical steroids upon blood and tissue sulfhydryl levels (Binet and Poutonnet, 1943; Hess et al., 1951; Goldzieher et al., 1953a; Goldzieher et al, 1953b), the effect of sulfhydryl and disulfide compounds upon corticoid output has been little studied. Carey et al. (1951) reported that large doses of glutathione depleted rat and guinea pig adrenal ascorbic acid and cholesterol. Bacq et at. (1953) demonstrated a large fall in adrenal ascorbate after administration of 2-aminoethanethiol (cysteamine) but no change in cholesterol content. Goldzieher and Edlin (1953) found a fall in urinary 17-keto and reducing steriods after prolonged treatment with cystine. The purpose of the present study was to observe the effect of a number of sulfur compounds and sulfhydryl-binding inhibitors upon the in vitro formaldehydogenic steroid output of rat adrenal glands.

Observations on in vitro adrenal steroid synthesis in the rat.

The in vitro production of adreno-cortical steroids has been demonstrated in the rat by Saffran et al. (1952), in the cow by Haynes et al. (1952b) and in the dog by Brady (1953). Both Saffran et al. and Haynes et al. were also able to demonstrate an in vitro stimulatory effect of ACTH on corticoid output. In the work about to be reported, we have endeavored to evaluate the effects of various compounds on the in vitro formation of steroids by rat adrenal glands. MATERIALS AND METHODS Female rats of the Sprague-Dawley strain, weighing about 150 gm., were used in the experiments described below. The incubation procedure was as follows: the animals were sacrificed by manual separation of the cervical vertebrae and the adrenal glands obtained as rapidly thereafter as possible. The glands were cleaned of adherent tissues, weighed on a Roller-Smith torsion balance and cut into quarters with a razor blade.

Long-term clinical and metabolic observations in periodic catatonia.

A detailed, metabolic investigation has been conducted in 3 cases of periodic catatonia over a period of 2-3 years. Case 1, a woman whose illness dated back to 1939 and who for 3 years prior to the present study had experienced recurrent violent excitements, was found to have changes in basal metabolic rate and nitrogen excretion correlating with her phasic changes. The disturbance has been brought under control by treatment with thyroid hormone and she has returned to work. Case 2, a man whose periodic psychotic excitements date back to 1936, was found to have a relative deficiency in 17-ketosteroid excretion with normal corticoid output. ACTH caused a normal adrenal response only in the corticoid fraction. This patient also had a low basal rate of oxygen utilization during interval periods and thyroid medication has brought his illness under control. Case 3, a woman with recurrent attacks of stupor since 1945, was found to have a relative excess of 17-ketosteroids in her urine with marked increases just prior to the onset of the deep retardation. The adrenal response to ACTH was relatively good, with a somewhat greater increase in corticoids than in 17-ketosteroids. Preliminary trials with cortisone improved her mental state and may provide specific, corrective therapy in this case. The possible significance of the low rate of oxygen utilization and its relationship to a state of hormonal imbalance are discussed. The importance of a careful determination of the hormonal pattern is stressed, if the causes of certain types of mental illness are to be understood and the success of specific, corrective therapy is to be evaluated.

Neutral steroid excretion by normal and by schizophrenic men.

IN PREVIOUS papers the demonstration of abnormal adrenocortical response to stress and ACTH by schizophrenic men has been made (1, 2, 3). As possible explanations of the apparent diminished responsiveness in a large proportion of the schizophrenic subjects we have suggested: a) a tendency for the rapid inactivation of either endogenous or exogenous ACTH in schizophrenics or b) limited steroidogenesis by the schizophrenics' adrenal cortices in response to increased circulating ACTH from either exogenous or endogenous sources. Although excessive ACTH inactivation cannot be overlooked, certain considerations suggest that abnormal steroidogenesis in response to ACTH may occur in schizophrenic men. The fact that the total basal 17-ketosteroid output of schizophrenic men equals or exceeds that of nonpsychotic men of the same age, whereas the basal corticosteroid output (measured as neutral reducing lipid) is significantly lower in schizophrenic men, suggests a differential rate of secretion of the adrenal precu...

Adrenotropic hormone (ACTH), aminopterin and eosinophil count.

RECENT experiments indicate that a relationship might exist between aminopterin and adrenal cortex function. Dougherty and Dougherty1 report that, following adrenalectomy, mice do not show the lymphopænia and acute atrophy of lymphatic tissue which are observed following a lethal dose of aminopterin. Higgins2, using aminopterin and aminoteropterin, showed that adrenalectomy minimized considerably the changes induced by such drugs within the spleen, the thymus gland, the peripheral blood and bone marrow of rats. They assumed that some effects of aminopterin can be due to a stimulation of the adrenal cortex. On the other hand, Hanlon3 of the Mayo Clinic has observed that aminopterin in human subjects gives a rather marked decrease in the output of corticosteroids and, in no case, an increase.

A Biometric Study of the Excretion of Corticosteroids in Children in Relation to Age, Height and Weight

rJHIS STUDY is based on data made available in an investigation by -IKing and Mason (Ref. 1) in which the urinary excretion of corticosteroids was determined for 87 normal children (28 boys, 59 girls) including newly born babies and children up to 16 years of age. On approximately the same day as the urine was collected for the determination of the corticosteroids, measurements of height and weight without clothes were made. Urine was collected during twenty-four hours in glass bottles without preservative. The parents and the children were instructed as to the necessity of accurate collection of the urine. They were questioned afterward and if there was any doubt as to the accuracy of the collection, the specimen was discarded. The method for the determination of the corticosteroids has been described by Corcoran and Page (Ref. 2). The values for the urinary corticosteroids are expressed as milligrams of 11-dehydrocorticosterone per twenty-four hours. The mean corticosteroid output per twenty-four hours increases steadily with age (fig. 1). Since, however, during this period the weight and the height are both increasing, it is pertinent to inquire whether the increase of output is related to either or both of these, rather than to age per se. Talbot (Ref. 3) reported that if the output of corticosteroids is expressed in ratio to surface area, the surface area being measured by the formula of DuBois (S. A. = 0.00718 WO0 425 H0 725), the output does not change with age. This finding we (lid not confirm in our data. The mean