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[An ACTH-like peptide immunocortin: effect on the activity of cells from the rat adrenal cortex].

The effect of immunocortin, an ACTH-like decapeptide VKKPGSSVKV corresponding to the 11-20 sequence of the variable part of the human IgG1 heavy chain on the content of 11-hydroxycorticosteroids (CS) in rat adrenal glands and blood serum in vivo was studied. An intramuscular injection of immunocortin at a dose of 10 microg/kg was found in an hour to induce a twofold decrease in CS content in the adrenal glands and a 1.8-fold increase in the blood serum CS content. At the same time, an immunocortin dose of 100 microg/kg exerted practically no effect on the CS content and its dose of 1000 microg/kg increased the CS content both in adrenal glands and in blood serum by 1.6 and 2.2 times, respectively. Four hours after the injection of any of the three doses of immunocortin, the CS content in adrenal glands did not differ from the control value, and after 24 h the content decreased threefold. Immunocortin was shown to be bound by the ACTH receptors in the membranes of the rat adrenal cortex with a high affinity and specificity (inhibiting the specific binding of 125I-labeled ACTH-(11-24) peptide with Ki of 1.2 nM).

11-Hydroxycorticosteroids↗

Suicide risk factors in depressive disorders and in panic disorder.

Suicide has been associated traditionally with major depression, alcoholism, and schizophrenia and in the past several years with alcoholism and comorbid depression. More recently, however, panic disorder has been linked with suicide attempts, and the importance of severe anxiety symptoms (panic attacks, psychic anxiety, and agitation) as possible predictors of suicide risk in patients with major affective disorder has been studied. The author discusses data sets from three such studies: (1) the Clinical Studies of the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression, (2) a study on 17-hydroxycorticosteroid concentrations in inpatients with major affective disorder, and (3) a study on inpatient suicides. The author concludes by suggesting that anxiety, which is readily treatable, may in fact be one of the most clinically important symptoms in depressive disorders.

17-Hydroxycorticosteroids↗

Hypogonadism in Prader-Willi syndrome.

Sexual development was evaluated in 9 female and 2 male subjects with Prader-Willi syndrome. The process of sexual development and degree of genital development attained were found to be variable but abnormal in all subjects. Hypothalamic-pituitary-gonadal functions were evaluated by measurement of serum Luteinizing Hormone and plasma testosterone responses to stimulation by clomiphene citrate and plasma testosterone responses to stimulation by human chorionic gonadotrophin. The degree of vaginal estrogenization was variable. The testicular biopsies showed abnormalities mainly in the germinal epithelium. In agreement with previous studies, it was concluded that the abnormalities of sexual development in this syndrome are mainly due to a defect in the hypothalamic pituitary axis. Adrenal function was not found to be grossly abnormal. The 17 ketosteroid excretion values were low, probably explaining the rather sparse pubic and axillary hair observed in these patients. The urinary 17-hydroxycorticosteroid creatinine ratios were found to be elevated, probably due to decreased creatinine excretion, reflecting the muscular abnormalities of these subjects.

17-Hydroxycorticosteroids↗

[Treatment of climacteric syndrome with new gengnian prescriptions].

It was found by the observations of clinical treatment that the three indexes of epinephrine(E), norepinephrine(NE) and dopamine(D) of urinary catecholamine(CA) increased (P less than 0.001, P less than 0.05 and P less than 0.001) for the climacteric patients who suffered from the deficiency of Yin leading to the hyperactivity of the internal heat of the heart, and the urinary 17-hydroxycorticosteroid (17-OHCS) increased (P less than 0.001) for the patients who suffered from the deficiency of Yin leading to the hyperactivity of the internal heat of the liver. Both the three indexes and urinary 17-OHCS increased for the two groups (P less than 0.01). However, for all the above groups who suffered from the deficiency of Yin leading to the hyperactivity of the internal heat, the NE/E ratio was larger than the normal ratio, which stands for the level of central catecholamine. After the treatment with new Gengnian prescriptions, the clinical symptoms of the patients were improved, and in the meantime urinary CA. 17-OHCS and NE/E were decreased. The total efficiency was 89.2%. The principle of treatment with this prescription may be due to the fact that the level of central catecholamine decreased so that the excessive excitation of sympathetics-adrenocortical system and sympathetics-adrenocortical system was restrained.

17-Hydroxycorticosteroids↗

[Osteocalcin--a marker of bone metabolism and calcium regulating hormones in steroid osteoporosis].

Altogether 15 patients with Itsenko-Cushing disease with moderate osteoporosis and 10 healthy persons were investigated. Calcium metabolism, calcium regulating hormones and osteocalcin were studied. Endogenous hypercorticoidism was characterized by a higher secretion of parathyroid hormone against a background of hypercalcemia. Positive correlation of these indices was revealed. In patients with Itsenko-Cushing disease the blood level of vitamin D was decreased as compared to that in the controls. A significant decrease in the blood level of osteocalcin was observed in patients with endogenous hypercorticoidism, there being close negative correlation between the level of osteocalcin and cortisol, and between osteocalcin and 17-hydroxycorticosteroid excretion with urine. A conclusion has been made that the excess of glucocorticosteroids suppresses osteoblast function, slows, down osteogenesis, disturbs the secretion of calcium regulating hormones and calcium metabolism enhancing resorption; this combined action of glucocorticoids causes rapid development of osteoporosis in endogenous hypercorticoidism.

17-Hydroxycorticosteroids↗

[Corticoid secretion and patho-histological changes in the adrenal glands in hypertension].

Hydrocortisone, 11-hydroxycorticosteroids and aldosterone were measured in 74 patients with a history of surgery on the sympathoadrenal system for stable essential hypertension. Morphologic structure of the sympathetic ganglia of the celiac plexus and adrenals removed during surgery was under study. The studies have revealed a relationship between pathohistologic changes in operation material and adrenocortical functional activity. The authors suggest a possibility of a relationship between morphofunctional changes in the adrenals and sympathetic ganglia, and enhanced nervous system efferent effects with the progress of the disease.

11-Hydroxycorticosteroids↗

[The effect of serotonin on the hypothalamic structures that participate in the regulation of the hypophyseal-adrenal cortex system].

The activation of the 11-hydroxycorticosteroids secretion by 5-hydroxytryptophan was confirmed in intact rats as well as in those with isolated mediobasal hypothalamus. Deafferentation of the medial basal hypothalamus did not prevent an increase of corticoliberin and vasopressin content in the external median eminence after adrenalectomy and led to an opposite response after 5-hydroxytryptophan injection in these rats. The activation of the vasopressinergic cells and increase of portal vessels' lumen occurred under the 5-hydroxytryptophan effect, particularly in rats subjected to deafferentation combined with adrenalectomy.

11-Hydroxycorticosteroids↗

Stress-induced cortisol release in hypothalamic hypoadrenalism.

A 52-year-old woman experienced hypoadrenalism (mean 8 AM plasma cortisol level, 3.7 microgram/dL) after hypothalamic surgery and radiotherapy for craniopharyngioma. Despite low plasma adrenocorticotropic hormone levels (less than 25 pg/mL), absent diurnal variation of the plasma cortisol level, and subnormal urinary 17-hydroxycorticosteroid response to metyrapone, she had normal plasma cortisol responses to insulin-induced hypoglycemia and to administration of vasopressin or synthetic adrenocorticotropic hormone. Stress-induced cortical release may be preserved despite notable abnormalities in regulation of cortisol secretion by diurnal and feedback-mediated mechanisms.

17-Hydroxycorticosteroids↗

[The direct stimulating effect of arginine vasotocin on the functional activity of the interrenal gland in the frog Rana temporaria].

Using radioimmunoassay it has been detected that both nonoperated and hypophysectomized, lacking endogenous ACTH, frogs injected one or three times with arginine vasotocin (5.10(-9) M/kg b. w.) show a statistically significant increase of plasma corticosterone level as compared with that in control animals and frogs injected with Ringer solution. The level of 11-hydroxycorticosteroids (fluorometric determination) in the interrenal gland decreases significantly only in animals three times injected with arginine vasotocin. It is assumed that arginine vasotocin produces a direct stimulatory effect on corticosteroid-producing cells of the frog interrenal gland.

11-Hydroxycorticosteroids↗

[The effect of halothane anesthesia on the function of the adrenal cortex and some metabolites in the blood plasma of pigs not susceptible to malignant hyperthermia].

The effects were investigated of a 25-minute inhalation of halothane with oxygen on three to four months old pigs of the Large White breed. Symptoms of malignant hyperthermia did not occur. The actual total anesthesia, which causes slight hypoproteinemia, hypoglycemia and hypocholesterolemia without significant changes in the content of non-esterified fatty acids (NEFA) and urea, induced only a slight increase of circulating 11-hydroxycorticosteroids (11-OHCS). The combination of anesthesia with castration of gilts or barrows significantly increased the concentration of 11-OHCS but did not reach the level recorded after the application of ACTH. The higher levels of 11-OHCS were accompanied by higher concentrations of NEFA and glucose. The treatment of the animals lasting half an hour prior to inhalation of halothane at maximum doses or one hour in the control unanesthetized pigs produced an effect, mainly on the 11-OHCS concentration and on the activity of creatine kinase in the plasma. The results indicate that the adrenocortical response to the effect of halothane is not stronger than the response to simple handling connected with excitement and muscular activity of the animals. Therefore there is no reason of considering halothane anesthesia as a factor causing great stress and pigs which in its course do not respond with malignant hyperthermia as animals insensitive to stress. The aptness of denotation of clinical manifestations of genetically defective muscles in pigs is discussed.

11-Hydroxycorticosteroids↗

[Genetic determination of the response of the mouse hypothalamo-hypophyseo-adrenal system to cold and immobilization stress].

Peculiarities of the hypothalamo-pituitary-adrenal system (HPAS) reaction in mice of 8 inbred strains to a stress effect of the immoblization and of cold have been studied and a comparison of the effect with the reaction of the adrenal cortex to its direct stimulator--ACTH have been carried out. As a result of the study of the resting level of 11-hydroxycorticosteroids in peripheral plasma of inbred mice significant interstrain differences were found. A positive correlation between resting corticosteroids level and the reaction of HPAS to the stress in mouse strains under study was found, but none of them correlated with the reactivity of the adrenal cortex to ACTH.

11-Hydroxycorticosteroids↗

[Changes in the functional state of the adrenal glands in experimental bronchospasm in dogs].

Changes in the adrenal functional state were revealed during the development of bronchoconstriction induced by allergen inhalation in 7 dogs sensitized with ovalbumin. The decrease in V1 (expiratory flow-volume) on an average by 58% was noted after inhalation of 1000 microG of ovalbumin. The significant decrease in II-hydroxycorticosteroids (II-OCS), adrenaline, noradrenaline, dopamine, and a tendency to the increase in histamine content were observed in the venous blood plasma. The decrease in the adrenaline content in plasma apparently contribute to the development of early bronchoconstrictor response, and the decrease in II-OCS maintain the development and the progress of late bronchoconstrictor response.

Adrenal Glands↗

[Biochemical changes in a decrease in the voluntary consumption of alcohol by rats due to lithium chloride].

A decrease of alcohol intake by ethanol-preferring rats under free choice conditions after intraperitoneal administration of lithium chloride (35 mg/kg) was accompanied by an activation of aldehyde dehydrogenase in the brain stem, a decrease of dopamine and salsolinol levels in the striatum and normalization of 11-hydroxycorticosteroids contents in the blood and adrenal glands.

11-Hydroxycorticosteroids↗

[A case of adrenal black adenoma associated with Cushing's syndrome].

A 36-year-old female was admitted to Asahi General Hospital because of hypertension. Laboratory findings showed elevated levels of urine 17 (11)-hydroxycorticosteroid and blood cortisol. Computerized tomography and ultrasound sonography demonstrated a round tumor at the suprarenal region. The black tumor, 5 X 3 X 2 cm, was removed by left adrenalectomy. Microscopic findings revealed adrenal adenoma consisting of compact cells containing numerous pigmented granules. Postoperative course was uneventful. Hormonal condition was recovered 11 months after operation.

17-Hydroxycorticosteroids↗

[Features of the functioning of the catecholamine and adrenocortical systems of patients with depression and different degrees of emotional tension].

The catecholamine and adrenocortical systems in 52 patients with depression were studied with regard to the degree of their emotional tension. On the basis of the clinical characteristics of the depressive syndrome the patients were divided into two groups: the stressory hyperergic type (Group 1) and the torpid hypoergic type (Group 2). Some characteristics of the studied systems proved common for both groups: they increased secretion of 11-hydroxycorticosteroids and impairment of the mechanisms of negative feedback in the regulation of adrenocortical activity, as well as a decrease in the excretion of dopamine, adrenaline, and DOPA in the presence of a relative acceleration of catecholamine inactivation. Along with the characteristics common for all the patients studied, the authors revealed a highly significant difference in noradrenaline excretion between Groups 1 and 2: it was normal in Group 1 and decreased three-fold in Group 2. The findings obtained are discussed in the light of the catecholamine hypothesis of depression development.

11-Hydroxycorticosteroids↗

Virilizing adrenocortical tumors in childhood: eight cases and a review of the literature.

Eight cases of adrenocortical tumor are presented with a review of the literature. Although such tumors are rare, they are important causes of inappropriate virilization and Cushing's syndrome in childhood. Clinical virilization with or without hypercortisolism was found in all eight children, who were 5 years old or younger. Excessive linear growth was noted, despite evidence of hypercortisolism. Serum levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, testosterone, and cortisol were elevated in all cases tested and appear to be useful diagnostic alternatives to the more traditional determinations of urine 17-ketosteroids and 17-hydroxycorticosteroids. Abdominal sonography and computed tomography have proven to be reliable tools for tumor localization. Surgical resection was the definitive therapy in all patients, and perioperative steroid replacement was essential. Histologic diagnosis appeared to have little bearing on prognosis, and the majority of pediatric patients have had clinically benign disease. At a mean follow-up of 3 years, seven of the eight children were alive and had no evidence of tumor recurrence.

17-Hydroxycorticosteroids↗

The indoleamine hypothesis of depression: an overview and pilot study.

This paper reviews the evidence for a specific indoleamine deficiency in depression and the attempts to correct this suspected deficiency with serotonin precursors. It also presents the clinical and biochemical data on six patients with depression treated with L-5-HTP in a nonrandom, double-blind protocol. The oral administration of L5-HTP was associated with a rise in CSF5-HIAA, but only two of six patients studied had any decrease in depression ratings. 5-HTP was also shown to decrease urinary excretion of 17 hydroxycorticosteroids in twodepressed patients and three normal controls suggesting an interrelationship between serotonin metabolism and the pituitary adrenal system. This leads to the suggestion that in a postulated subgroup of depressed patients with pituitary adrenal hyperactivity and evidence of serotonin deficiency, L5-HTP deserves a further trial as an experimental treatment.

5-Hydroxytryptophan↗