Showing papers on "Adrenal cortex published in 1969"

Plasma Progesterone and 17-hydroxyprogesterone in normal men and children with congenital adrenal hyperplasia

Abstract: A B S T R A C T Plasma 17-hydroxyprogesterone (17OHP) concentrations in normal men averaged 0.094 ,ug/100 ml. Studies using suppressive doses of androgens and glucocorticoids showed that 90% of the 17-OHP originated from the Leydig cell. The 17-OHP production rate was 1.8 mg/24 hr. Plasma 17-OHP has a marked circadian variation, the 8 p.m. values being only 40% of the 8 a.m. values. Plasma luteinizing hormone measured in the same samples did not vary. The adrenal cortex has the capacity to synthesize and secrete 17-OHP and progesterone since adrenocorticotrophic hormone (ACTH) caused a fourfold increase in these plasma steroids. In children with congenital adrenal hyperplasia, plasma 17-OHP levels were 50200 times those of normal men and plasma progesterone was increased 6- to 10-fold over normal men.

The Mechanism of Action of Adrenocorticotropic Hormone

Abstract: Publisher Summary This chapter discusses the relationship of the structure of adrenocorticotropic hormone (ACTH) to its function and the pathway of adrenal cortical biosynthesis. A series of remarkable achievements in protein chemistry have led to the isolation and purification of ACTH, the determination of its primary structure, and its synthesis. The biochemical synthesis of adrenal corticosteroids with its many complexities is explained in the chapter. The influence of ACTH on the adrenal cortex is not limited to the stimulation of corticosteroid production; the maintenance of the structure of the adrenal cortex is also dependent upon this hormone. The removal of the pituitary gland from rats resulted in the atrophy of the adrenal cortex and that the transplantation of the pituitary to hypophysectomized animals caused a return of adrenal cortical weight toward normal. The synthesis of glucocorticoids in the adrenal cortex is accomplished by a series of enzymes situated in different organelles. The evidence indicates that the first substrate, cholesterol, enters the mitochondrion where it is transformed into pregnenolone. Pregnenolone leaves the mitochondrion and is converted into progesterone in the cytoplasm. Progesterone, in turn, is transformed into deoxycorticosterone by an enzyme system in the microsomal fraction of the cell. Corticosterone is produced finally from deoxycorticosterone that has reentered the mitochondrion.

Fundamentals of clinical endocrinology

Abstract: Anterior pituitary, G.M.Besser posterior pituitary, G.M.Besser hypothalamus, G.M.Besser disorders of growth, M.O.Savage thyroid, R.Hall adrenal cortex, P.Drury and G.M.Besser adrenal medulla, P.M-G.Bouloux and G.M.Bessemer congenital adrenal hyperplasia, I.A.Hughes ovary, hirsutism and virilism, M.F.Scanlon pregnancy, A.M.McGregor testis, F.Clark and W.K.Yeates precocious puberty, I.A.Hughes disorders of sexual differentiation, I.A.Hughes biochemical actions of hormones effects on intermediary metabolism, D.G.Johnston et al diabetes mellitus, D.G.Johnston et al hypoglycaemia, J.Anderson obesity, D.G.Johnston calcium, phosphate and parathyroid, J.Compston gastro-intestinal hormones, the syndromes of multiple endocrine neoplasia and carcinoid tumours, J.A.H.Wass ectopic hormones, J.A.H.Wass. Appendices: tests of hypothalamic-pituitary function growth and development tests of thyroid function tests of adrenocortical function tests of gonadal function body weights miscellaneous.

Adrenal cells in tissue culture. IV. Use of an inhibitor of steroid synthesis for the study of ACTH action.

Abstract: This report describes the use of aminoglutethimide (AG), an inhibitor of steroid synthesis, for the study of some effects of ACTH on the metabolism of functional monolayer cultures of murine adrenal cortex tumors. At concentrations in the medium of 10 μg/ml or higher, the drug specifically blocks steroid biosynthesis from cholesterol. At concentrations over 50 μg/ml it is also a competitive inhibitor of 11β-hydroxylation. Its action is immediate and reversible. Concentrations in excess of 100 μg/ml have no adverse effect on cell growth, RNA and protein synthesis, glycolysis or cholesterol synthesis. Four effects of ACTH which we have previously described were investigated: the steroidogenic response to ACTH, the augmentation of steroidogenesis by prolonged stimulation with ACTH, the increased synthesis of cholesterol from acetate, and the stimulation of glycolytic activity. At concentrations over 10 μg/ml, both control and stimulated steroidogenic activity is blocked. At lower concentrations, the ratio of...

The further characterization of autoantibodies reactive with extra-adrenal steroid-producing cells in patients with adrenal disorders

Abstract: Antibodies reactive with the steroid-producing cells in the gonads are described in the sera of ten patients, the majority of whom were known to have idiopathic adrenal insufficiency (Addison's disease) associated with premature ovarian failure. The immunofluorescent staining pattern of these antibodies with steroid-producing cells in the ovary, testis, placenta and adrenal cortex are illustrated. The staining patterns and the results of absorption studies indicate that there are a multiplicity of antibodies reacting with different antigens in the ovary and to a lesser extent in the testis. Most of these antigens are also represented in the adrenal cortex, but are not evenly distributed throughout the cortex. Some of these antigens are not represented in the zona glomerulosa while others are not represented in the zona reticularis.

Adrenal secretion rates and adrenal tissue concentrations of pregnenolone, progesterone, 11βOH‐androstenedione and some other steroids in young pigs and dogs

Abstract: 1. The rates were measured at which a number of different steroids were secreted by the adrenal gland of the eviscerated and nephrectomized young pig and dog. 2. In addition to cortisol and corticosterone the following steroids were consistently found to be present in the adrenal venous blood: pregnenolone, progesterone, 11βOH-progesterone, androstenedione, 11βOH-androstenedione and adrenosterone. 3. The sum of the latter steroids could amount to as much as 30% of the total steroid secretion. 4. A severe deficit in the blood volume increased the secretion of pregnenolone and the 17-oxo steroids in the pig. 5. α-ethyltryptamine failed to inhibit ACTH release if the animals were eviscerated and nephrectomized, or if they were anaesthetized with chloralose instead of pentobarbitone sodium. 6. The same steroids as in the adrenal venous blood were found in extracts from the adrenal glands of a number of species. 7. The amount of individual steroids present in the adrenal gland of the stressed pig and dog was compared with the rate at which each had been secreted immediately before the excision of the gland. 8. There was a positive correlation between the adrenal concentrations and the secretion rates of cortisol, the major glucocorticoid secreted by the pig and the dog. 9. In contrast, the rate at which pregnenolone was secreted did not show a consistent relationship to its concentration in the gland. 10. A storage mechanism for pregnenolone in the adrenal cortex is proposed.

Effects of sodium deficiency, potassium deficiency and uremia upon the steroidogenic response of rat adrenal tissue to serotonin, potassium ions and adrenocorticotropin.

Abstract: Quartered adrenal glands of rats kept on a sodium-deficient diet or uremic after bilateral nephrectomy were found to produce more aldosterone and less deoxycorticosterone in vitro than adrenal tissue of normal rats. On the other hand, dietary potassium deficiency led to a decreased aldosterone production and an increased deoxycorticosterone production. These differences in corticosteroid production became especially marked when the adrenals were stimulated in vitro by serotonin, adrenocorticotropin (ACTH) or a high potassium concentration in the incubation medium. In adrenals of sodium-deficient or uremic rats aldosterone production was stimulated to the same extent by the addition of progesterone, deoxycorticosterone or corticosterone, whereas in normal adrenal tissue aldosterone production was highest when corticosterone was added to the incubation medium. Only added corticosterone significantly stimulated aldosterone production in adrenals of potassium-deficient rats. These results indicate that the st...

Inhibition of the effects of angiotensin ii on adrenal steroid production by dietary sodium

Abstract: The pressor octapeptide, angiotensin II, can stimulate the production of aldosterone by the adrenal cortex. The present results show that in the dog a high-sodium diet can eliminate the steroidogenic action of angiotensin II, which is thus dissociated from the pressor action which remains. Angiotensin II was infused intravenously for 48 hours into conscious, undisturbed hypophysectomized dogs that were receiving each day either 60 or 200 mEq of dietary sodium. Blood pressure and secretion of aldosterone, corticosterone, and cortisol were measured (1) throughout the infusion in some dogs, and (2) at the end of the infusion in all dogs. In those dogs receiving 60 mEq of sodium, angiotensin II elevated the blood pressure and produced sustained increases of secretion of aldosterone, corticosterone, and cortisol. In those dogs receiving 200 mEq of sodium, angiotensin II, while retaining its pressor activity, had no effect on the production of aldosterone, corticosterone, or cortisol after 24 hours. Thus, if angiotensin II can produce hypertension clinically, there need not be secondary aldosteronism as well.

Studies on the biosynthesis of aldosterone in solitary adenoma and in nodular hyperplasia of the adrenal cortex in patients exhibiting conn's syndrome

Abstract: The pattern of aldosterone biosynthesis in solitary (primary) adrenal cortical adenomata and in nodular adrenal hyperplasia in patients exhibiting Conn's-syndrome was studied by incubation in the presence of 4-14C-progesterone. The production of radioactive aldosterone and 18\\x=req-\\ hydroxycorticosterone in solitary adenomata was considerably higher than in the surrounding tissue, indicating increased 18-hydroxylase activity. This could be responsible for the hypersecretion of aldosterone in Conn's-syndrome due to primary adenoma. The formation of 14C\\x=req-\\ aldosterone and 14C-18-OH-corticosterone in adrenal tissue with micro\\x=req-\\ or macronodular hyperplasia was minimal, indicating an absence of the substrate (corticosterone) specific 18-hydroxylase hyperactivity. The mechanism of the hyperaldosteronism in patients with nodular hyperplastic adrenal, is not clear. Two possibilities are discussed: a) hyperfunction of the synthesis in a phase prior to progesterone. b) hyperactivity of the biosynthesis pathways of aldosterone bypassing progesterone and corticosterone. Studies on the content and biosynthesis of aldosterone from endogenous pre¬ cursors in solitary adenomas of Conn-syndrome patients were published by Bailey et al. (1960), Dyrenfurth et al. (1960), Louis Sc Conn (1961), Biglieri et al. (1963) and Kumagai et al. (1963). Recently, cases have been reported Presented in part at the 14th Annual Meeting of the German Society of Endocrinology, Heidelberg, 1968. Downloaded from Bioscientifica.com at 09/04/2018 05:09:26PM via free access imitating the clinical picture of Conn's-syndrome, with hypertension, aldo¬ sterone hypersécrétion etc., in which a nodular hyperplastic alteration of the adrenals was found (Davis et al. 1967; Katz 1967; Wolff et al. 1968 ,&; Ditoni Se Städtler 1968). It was assumed that this alteration of the adrenals can be caused by the hyperfunction of an unidentified regulating mechanism inde¬ pendent of ACTH and the renin-angiotensin-system. The mechanisms regulating aldosterone secretion act either at the biosyn¬ thesis levels prior to progesterone (ACTH and angiotensin) or between pro¬ gesterone and aldosterone (Na-depletion and K-excess). It seemed of interest to study the aldosterone biosynthesis patterns by the incubation of adrenal tissue with solitary adenoma and with nodular hyperplasia, in the presence of 14C-progesterone. MATERIALS AND METHODS Adrenal tissue was obtained immediately after removal. Slices (100-200 mg) of the adrenal glands with nodular hyperplasia or primary adenoma as well as the sur¬ rounding tissue were incubated in 10 ml Krebs-Ringer-bicarbonate-glucose solution at 37°C for 4 h with 0.1 ,aCi/100 mg 4-14C-progesterone (spec, activity: 71 ,aCi/mg, New England Nuclear Corp., Boston), without any preincubation. At the end of the in¬ cubation period the incubation fluid was extracted with chloroform and the radio¬ active corticosteroids were isolated by repeated chromatography (Fig. 1). Slight modi¬ fication of the isolation procedure was occasionally necessary, because of the presence of unidentified steroids. The identity of the isolated radioactive aldosterone, cortisol, cortisone, compound S and corticosterone was confirmed by the stability of the 14C/3H quotients in two or three of the last Chromatographie systems. For this purpose 3H-labeIled variants of these corticosteroids were added to the samples before extraction or after the first Chromatographie steps. In the absence of suitable 3H-labelled steroids, an identification procedure of this kind could not be performed for 6-OH-corticosterone and 18-OHcorticosterone. The identity of these radioactive compounds was controlled by the 7?p-values. In the last Chromatographie systems these radioactive steroids were found to be homogeneous. The formation of the radioactive corticosteroids was expressed in percentages of the progesterone-14C-activity, added to the incubation medium. Patients, whose adrenals were removed, showed clinical findings typical of Conn'ssyndrome: i. e. hypertension, increased aldosterone secretion and suppressed plasma renin concentration. Table 1 summarizes some of the clinical and morphological data. Further details have been published elsewhere (Wolff et al. 1968t7,5, 1969; Dhom 8c Städtler 1968).

The occurrence of tubular intramitochondrial inclusions in the post-mortem zona fasciculata of the rat adrenal.

Abstract: Adult male albino rats are decapitated and the mitochondria in one adrenal gland are examined at increasing post-mortem time intervals in the electron microscope. The contralateral adrenal gland is excised rapidly, immersed in aldehyde fixative, diced, and used as the control. As early as 15 minutes postmortem, tightly packed sheaves of tubules (each tubule measuring 140 AR in outside diameter) appear as inclusions in the matrix of mitochondria within the zona fasciculata. These inclusions occur in increasing numbers of mitochondria during the first hour postmortem, until 10-25% of the mitochondria examined contain at least one sheaf of tubules. Observations at two and three hours post-mortem reveal no significant increase in inclusion-containing mitochondria. At these late time intervals additional post-mortem alterations are evident: (1) a decrease in mitochondrial matrix density; (2) swelling of mitochondrial cristae; and (3) vesiculation of the smooth reticulum. Kjaerheim ('67), Wheatley ('68), and Magalhaes and Magalhaes ('68) have described tubular inclusions in the matrix of “normal” rat adrenal mitochondria which are identical to the post-mortem inclusions described in this study. The presence of such inclusions in control mitochondria has been observed by the author on one occasion: within a degenerate mitochondrion enclosed inside a cytoplasmic membrane-limited vacuole. The possible significance of this post-mortem mitochondrial alteration in the rat adrenal cortex is discussed.

Interconversion of Cortisol and Cortisone in Man and Its Effect on the Measurement of Cortisol Secretion Rate

Abstract: Following intravenous injection of tracer doses of 4-14C-cortisol and 1,2-3H-cortisone, urinary metabolites of cortisone and cortisol were extracted and purified in 3 normal adult subjects, 1 child and 2 adult men treated with ACTH. Study of the 3H/14C ratio in the different metabolites and their specific activity as related to 14C and to 3H showed that there is extensive but not complete interconversion between cortisol and cortisone. Although the data obtained are those expected if cortisol alone was secreted by the adrenal cortex of the subjects studied, the lack of sensitivity of the theoretical model employed did not permit us to exclude cortisone secretion.

Studies on the Efficiency of Adrenocortical 11β-Hydroxylation in the Human Subject

Abstract: The efficiency of 11β-hydroxylation by the adrenal cortex was studied in normal subjects, women with hirsutism and/or virilism and patients with various types of adrenocortical hyperfunction by simultaneous measurement of the secretory rates of cortisol (F) and 11-deoxycortisol (S).2 The ratio F/F+S×100 was found to be 95.1 ±2.2 in subjects without abnormalities in 11β-hydroxylation. This ratio was not altered by the administration of ACTH nor in 8 subjects with Cushing's syndrome due to nontumorous adrenocortical hyperfunction. Decreases in the ratio were found in 2 subjects with adrenocortical carcinoma, in 1 patient with Cushing's syndrome secondary to a bronchogenic carcinoma, in 1 of 2 subjects with Cushing's syndrome due to an adrenocortical adenoma, and in 2 patients given SK&F-12185, an 11β-hydroxylation inhibitor.

Ultrastructural zonation of the human adrenal cortex.

Abstract: Electron microscopic observations of sections from adrenal cortex obtained from a twenty-four-year-old male with hypertension were made. In the zona glomerulosa the cells showed a large nuclear-cytoplasmic ratio. The mitochondria had a dark matrix and plate-like inner structure. The agranular endoplasmic reticulum revealed a close association with lipid granules. The Golgi apparatus was prominent and frequently accompanied by centrioles. Free ribosomes were abundant. The zona fasciculata can be subdivided into two layers. In the outer layer the cells are characterized by numerous large lipid granules. Two kinds of mitochondria are discernible; one with a pale matrix and tubulo-vesicular or vesicular inner structure and the other with a dark matrix and tubulo-vesicular or lamelllform cristae. In the inner zona fasciculata and reticularis there are two types of cells besides the dark cells. The type 1 cells have a compact cytoplasm, elliptic or irregularly shaped mitochondria with a dark matrix and tubulo-vesicular or vesicular internal structure. The type 2 cells are large and ovoid, having a clear transparent cytoplasm. The mitochondria are numerous having a clear matrix and almost exclusively vesicular inner elements. Abundance in agranular endoplasmic reticulum, decreased lipid granules, and cytoplasmic incisions are common in both the inner fasciculata and reticularis. In addition the zona reticularis is characterized by increased number of dark cells, numerous pigment bodies, and the appearance of huge mitochondria. On the basis of these observation were discussed the significance of the organelles in steroid biosynthesis, mode of hormone secretion, and cyto-genesls in the adrenal cortex.

Actinomycin D in vivo: paradoxical and nonspecific effects on adrenal cortex.

Abstract: Previous, apparently contradictory reports of the effects of actinomycin D on adrenal corticosteroid production encouraged the present investigation of the consequences in vivo of a single administration to guinea pigs of a small dose (10–15 μg/100 g body weight). Within 2 days, base line plasma cortisol levels and urinary corticoids rose, and the effect of exogenous ACTH was curtailed. In the next several days, as base line values fell, the influence of ACTH on plasma cortisol was potentiated. The effect of the antibiotic on RNA synthesis was also biphasic: Synthesis was depressed for 36 hr but then rapidly recovered, so much so that both 32P incorporation into cytoplasmic RNA and the net amount of adrenal RNA rebounded significantly above control levels. These results cannot be regarded as consequences of the inhibition of RNA synthesis by actinomycin, for they were accompanied by net losses of protein and DNA and by histological evidence of cytotoxicity in the adrenal cortex. A review of many of the ef...

Effects of social stimuli on the adrenal cortex in male mice

Abstract: Male mice were housed either in wire-mesh cages placed adjacent to one another or in similar cages separated by wooden partitions. A higher level of adrenocortical function, measured by relative adrenal weights and adrenal ascorbic acid depletion, was found in the mice which had been allowed partial social contact. These results demonstrate that the adrenal cortex not only responds to social stimuli traditionally regarded as stressors but is also sensitive to more subtle changes in the social invironment.

Fetal Secretion of Glucocorticoids

Abstract: This report comprises a study of the quantitative secretion of cortisol and corticosterone by the dog fetus in utero. Fetal adrenal cannulation was performed without amniotic fluid loss using intrauterine surgical techniques. After cannulation, an adrenal sample was collected. ACTH was administered intravenously to the fetus and 3 min thereafter a second adrenal sample was collected. Fetal peripheral arterial blood was drawn as soon as possible after the second adrenal sample. Fetal body and adrenal weights were determined. Plasma samples were analyzed for cortisol and corticosterone by a modification of the double isotope derivative method of Kliman and Peterson. Calculated results for both steroids included adrenal and peripheral arterial concentrations and simple secretory rates and secretory rates relative to adrenal and fetal body weights corrected for systemic steroid concentrations. The concentration of cortisol and corticosterone was higher in theadrenal effluent than in the peripheral blood, whic...