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Showing papers on "Adrenal cortex published in 1970"


Journal ArticleDOI
TL;DR: This study demonstrates directly the binding of ACTH to its biologically significant site in direct proportion to their biological activity.
Abstract: Pure monoiodo ACTH-(125)I was prepared that was biologically active and free of unlabeled ACTH. Extracts of adrenal cortex that contained ACTH-sensitive adenyl cyclase, bound ACTH-(125)I; extracts that lacked the ACTH-sensitive cyclase did not bind ACTH-(125)I. Unlabeled ACTH inhibited the binding of ACTH-(125)I. Five ACTH derivatives which varied widely in biological activity were tested. All inhibited the binding of ACTH-(125)I in direct proportion to their biological activity. Albumin, insulin, and four unrelated iodinated hormones were inert. The addition of excess hormone or acetic acid produced rapid dissociation of bound ACTH-(125)I. This study demonstrates directly the binding of ACTH to its biologically significant site.

280 citations


Journal ArticleDOI
TL;DR: It was of considerable importance to establish whether a similar pattern of secretion existed in Cushing's syndrome due to bilateral adrenal hyperplasia to resolve the problem with the fin...
Abstract: It has recently been demonstrated that the total daily production of cortisol by normal man is accomplished in a series of discontinuous secretory episodes (Fig 1) separated by periods of quiescence of the adrenal cortex (1). In the normal it was shown that the adrenals did not secrete cortisol for about 18 hours of each day. The proof was based upon measurement of the specific activity of plasma cortisol in association with rises and falls in the plasma cortisol concentration measured at brief intervals. Rises in plasma level were accompanied by drops in cortisol specific activities while falls were associated with unchanged specific activity. It was also demonstrated that this episodic secretory activity persisted throughout the 24 hour sleep-awake cycle. It was of considerable importance to establish whether a similar pattern of secretion existed in Cushing's syndrome due to bilateral adrenal hyperplasia. It has been possible to study a carefully selected patient and to resolve the problem with the fin...

77 citations


Journal ArticleDOI
TL;DR: It is proposed that the reticulum decrement is the result of a reduced synthesis of new membranes, due to an inhibition of protein-synthesis in adrenocortical cells.
Abstract: The ultrastructural changes occuring in adrenocortical cells of prednisolone-treated rats were evaluated by morphometric methods. They consist mostly in a conspicuous decrease in the smooth reticulum surface and in the lipid droplets. The diminution of the smooth reticulum accounts for about 60 % of the decrement in cellular volume and in adrenal weight. Since numerous enzymes of corticosteroid-synthesis are localized in the microsomal fraction of adrenocortical cells, it is reasonable to suggest that the decrement of these organelles is the morphological expression of the cellular deficit in hormone-synthesis. The possible mechanism of reduction of the reticulum membranes is discussed in relation to the probable regulation mechanism of the adrenocortical secretion. It is proposed that the reticulum decrement is the result of a reduced synthesis of new membranes, due to an inhibition of protein-synthesis in adrenocortical cells.

69 citations


Journal ArticleDOI
TL;DR: PGE1 did not affect adrenal ascorbic acid in cortisol-pretreated intact rats or in 24-hr hypophysectomized rats, indicating that it has no ACTH-like effect on the adrenal cortex but acts by stimulating ACTH release.
Abstract: Prostaglandin E1 (PGE1) depleted adrenal ascorbic acid and cholesterol and increased plasma and adrenal corticosterone in rats. The log dose relationship between PGE1 iv and adrenal ascorbic acid concentration was linear between 0.5 and 2.0 μg. PGE1 was relatively specific since PGA1 and PGF2a did not deplete adrenal ascorbic acid at doses 10 times that of PGE1 and the respective vasopressor and vasodilator activities of the 3 prostaglandins did not correlate with capacity to stimulate the adrenal cortex. PGE1 did not affect adrenal ascorbic acid in cortisol-pretreated intact rats or in 24-hr hypophysectomized rats, indicating that it has no ACTH-like effect on the adrenal cortex but acts by stimulating ACTH release. Morphine strongly inhibited the adrenal ascorbic acid response to PGE1 in intact rats anesthetized with pentobarbital, indicating that the action of PGE1 on ACTH release is not direct on the anterior pituitary gland but is at some level in the central nervous system, possibly the hypothalamus...

62 citations



Journal ArticleDOI
01 Jul 1970-Steroids
TL;DR: 19-Iodocholesterol- 125 I was synthesized for study as a possible agent for photoscanning the adrenal gland and associated tumors and was found to be much less prone to rapid in vivo deiodination.

59 citations


Journal ArticleDOI
TL;DR: Comparison of outputs from bisected whole glands, capsular and decapsulated tissue has shown that 3 of the 4 steroids examined were produced to some extent by both zones of the adrenal cortex but aldosterone production was restricted to the zona glomerulosa under all conditions studied.
Abstract: Steroid output from adrenals of normal intact rats and rats 3 hr and 2 days after hypophysectomy has been measured during continuous superfusion in vitro (1, 2). Comparison of outputs from bisected whole glands, capsular (fibrous capsule plus mainly zona glomerulosa) and decapsulated (mainly zona fasciculata-reticularis plus medulla) tissue has shown that 3 of the 4 steroids examined, 18-hydroxy-β4, 18-hydroxy-DOC and corticosterone, were produced to some extent by both zones of the adrenal cortex but aldosterone production was restricted to the zona glomerulosa under all conditions studied. A reproducible decline in steroid output with time of superfusion was observed for all 3 types of tissue taken from normal intact rats. Three and 48 hr after hypophysectomy the production of the 3 steroids by the zona fasciculata was lowered and the decay virtually abolished. A continuous infusion of ACTH (60 mU/ml medium) maintained steroid output from the zona fasciculata of intact rats at the high initial level for...

52 citations


Journal ArticleDOI
TL;DR: Results indicate a zone specificity of certain stimulators and confirm that they act at an early stage in the corticosteroid biosynthetic pathway preceding the formation of deoxycorticosterone.
Abstract: Capsular and decapsulated adrenal glands of rats kept on different diets were separately incubated with and without stimulators of aldosterone biosynthesis. The steroidogenic effect of serotonin, potassium ions and angiotensin II was limited to the capsular portion (zona glomerulosa), whereas ACTH and cyclic AMP acted on both the capsular and the decapsulated portion (zona fasciculata-reticularis) of the adrenal cortex. In capsular adrenal glands of normal and sodium-deficient rats all these agents stimulated aldosterone production severalfold and had a smaller effect on corticosterone output. Sodium deficiency led to a decreased response in corticosterone and deoxycorticosterone output. In capsular glands of potassium-deficient rats the stimulators did not enhance aldosterone production but actsd mainly on deoxycorticosterone output. ACTH enhanced corticosteron e and deoxycorticosterone output to a similar extent in decapsulated glands of all groups of experimental animals. These results indicate a zone specificity of certain stimulators and confirm that they act at an early stage in the corticosteroid biosynthetic pathway preceding the formation of deoxycorticosterone. On the other hand, changes in sodium and potassium balance induce alterations in the activity of the enzymes involved in the conversion of deoxycorticosterone to aldosterone and thus influence the steroidogenic response of the zona glomerulosa to stimulating agents.

49 citations



Journal ArticleDOI
TL;DR: It is concluded that success in aggressive encounters, in contrast to defeat, does not contribute to the increased adrenocortical function found in grouped mice.
Abstract: Grouped laboratory mice (Mus musculus) show higher adrenocortical function than isolates, and this is usually attributed to the occurrence of aggressive behavior in such groups. the present experiment compares the effects of controlled bouts of fighting on adrenocortical function in trained fighter and defeated male mice. the results revealed increased adrenal function (compared with isolated controls) only in the latter condition; it is therefore concluded that success in aggressive encounters, in contrast to defeat, does not contribute to the increased adrenocortical function found in grouped mice.

41 citations


Journal ArticleDOI
TL;DR: A speculative proposal is made that the adrenal cortical cleavage of the isohexyl moiety of the cholesterol side-chain may proceed via 20α-hydroperoxide formation followed by enzymic rearrangement to 20α, 22 R -dihydroxycholesterol, which then undergoes bond cleavage between C-20 and C-22 to yield pregnenolone.

Journal ArticleDOI
TL;DR: Isolated cat adrenal glands were perfused with Locke solution, and the corticosteroid outputs in response to adrenocorticotrophin (ACTH) were studied.
Abstract: 1. Isolated cat adrenal glands were perfused with Locke solution, and the corticosteroid outputs in response to adrenocorticotrophin (ACTH) were studied. 2. Steroid outputs varied with the ACTH concentration, as well as with the duration of exposure to a given ACTH concentration. 3. Omission of calcium from the perfusion medium markedly depressed ACTH-evoked steroid release. The steroid output was directly related to the extracellular calcium concentration up to 0·5 mM. 4. During a constant exposure to ACTH, steroid output was maintained for at least 2-3 hr, provided that calcium was present in the perfusion medium. 5. Strontium, but not barium or magnesium, replaced calcium in maintaining the secretory response to ACTH. 6. Magnesium depressed ACTH-evoked secretion in the presence of calcium, and this depression of secretion was antagonized by increasing the calcium concentration. 7. Prolonged perfusion with sodium-free or potassium-free solutions did not markedly inhibit steroid output in response to ACTH. Excess potassium (56 mM) did not produce a consistent or marked increase in spontaneous steroid output and did not affect the response to ACTH. 8. The steroid content of adrenal glands perfused with Locke solution and exposed to ACTH was about 10% of the amount which was secreted. By contrast, adrenal glands perfused with calcium-free media and exposed to ACTH contained much higher amounts of steroid, despite the negligible amount secreted. 9. These data suggest that calcium plays a critical role in the mechanism of corticosteroid secretion from the adrenal cortex.

Journal ArticleDOI
TL;DR: The fine structure of adrenal cortices of opossums maintained on a sodium deficient diet for 21 days has been examined and the thickness of the zona glomerulosa is increased due to hypertrophy and hyperplasia of the parenchymal cells.
Abstract: The fine structure of adrenal cortices of opossums maintained on a sodium deficient diet for 21 days has been examined. After this treatment, the thickness of the zona glomerulosa is increased due to hypertrophy and hyperplasia of the parenchymal cells. After 21 days on the low sodium diet, the glomerulosa cells are characterized by large accumulations of smooth surfaced endoplasmic reticulum. This appearance is in marked contrast to the sparse representation of smooth surfaced reticulum in control animals. The rough surfaced endoplasmic reticulum becomes organized into long flattened cisternal profiles in parallel array and appears to be increased in quantity. The Golgi complex is also hypertrophied but marked changes in other organelles were not observed. Cells of the zona fasciculata appear to be unaffected by sodium depletion. Large lipid droplets accumulate in the zona reticularis of experimental animals but this zone is otherwise comparable to control animals. The bearing of these results on hypotheses of physiological control of secretion of the zona glomerulosa are discussed.

Journal ArticleDOI
TL;DR: The most important morphological parameter for assessing the activity of a steroid-secreting cell is the quantity of smooth endoplasmic reticulum, and it is possible to hypothesize that ACTH intervenes in the regulation of the mitochondrial RNA and DNA synthesis.
Abstract: The effects of corticosterone on adrenocortical cells of intact and hypophysectomized ACTH-treated rats were investigated by morphometric and autoradiographic methods The data obtained in these experiments allow us to make the following conclusions:

Journal ArticleDOI
TL;DR: The combination of reaction inhibition and of incorporation of tritium into cholesterol 20α-hydroperoxide and 20α, 22R-dihydroxycholesterol suggest that both be important intermediates in the biosynthesis of pregnenolone from cholesterol.


Journal Article
TL;DR: A case of primary hypothyroidism, idiopathic Addison's disease, idypathic hypoparathyroidism (with preceding moniliasis), Addisonian pernicious anaemia and primary ovarian failure is described.
Abstract: A case of primary hypothyroidism, idiopathic Addison's disease, idiopathic hypoparathyroidism (with preceding moniliasis), Addisonian pernicious anaemia and primary ovarian failure is described. She died at the age of 24 years following an illness compatible with adrenal crisis. At post-mortem there was no recognizable adrenal or ovarian tissue; there was only a minute portion of probable parathyroid tissue and the uterus was infantile. Her serum contained antibodies reactive with adrenal cortex, steroid-producing cells in the gonads, placental trophoblasts and thyroid epithelial cytoplasm and intrinsic factor. Her brother, who was known to have gluten enteropathy, died aged 11 years following an illness compatible with adrenal crisis. His adrenal glands were grossly atrophic at autopsy. The parents were consanguinous and both showed either clinical or serological evidence of organ specific autoimmune disease.


Journal ArticleDOI
TL;DR: Water and electrolytes in the extracellular and intracellular composition of the reptile Dipsosaurus dorsalis were examined and corticosterone prevented rise in plasma water and caused by a drop in muscle water content, but when cortic testosterone and prolactin were administered together, plasma and muscle composition was rendered normal.

Journal ArticleDOI
TL;DR: The hypothesis that at birth there is a partial degeneration of the rat zona juxtamedullaris, i.e. the zone corresponding to the “fetal zone” of some mammalian species, is supported by numerous data demonstrating that there are enzymatic conditions in the rat during fetal life, which permit a discrete hypertrophy of the adrenal cortex.
Abstract: The structural changes of the zona juxtamedullaris of the rat adrenal cortex at birth, have been examined by the light and the electron microscope. In this zone clusters of medullary cells lying among the strands of cortical tissue were observed. In the inner portion of the zona juxtamedullaris two types of adrenocortical cells were found: light and very-dark cells. The latter are smaller than the light cells and are always in close connection with the medullary tissue. The ultrastructural features of the very-dark cells suggest that these elements are in degeneration. This finding supports the hypothesis that at birth there is a partial degeneration of the rat zona juxtamedullaris, i.e. the zone corresponding to the “fetal zone” of some mammalian species.

Book ChapterDOI
01 Jan 1970
TL;DR: It is clear however that the demonstration that a particular steroid is synthesized in vitro or in vivo from a radioactive precursor gives no information about secretion; there are differences in the testicular secretory patterns among species so that extrapolation to man may not be warranted.
Abstract: To prove the secretion of a steroid, one must show that the venous effluent from the gland has a higher concentration of the steroid than has peripheral blood. This rigorous criterion is necessary since there is conversion among steroids in peripheral tissues as well as secretion by the adrenal cortex and gonads. There are, of course, important inferences that can be obtained about secretion without sampling the venous effluent by devising appropri ate experimental conditions both in vitro and in vivo. For example, the failure to demonstrate 11 s-hydroxylation in the normal testis and ovary under any conditions almost surely places the origin of the 11s -hydroxysteroids in the adrenal cortex. Suppression of adrenal cortical function in men does not alter plasma testosterone levels; thus testosterone must either be secreted by the testis or be a product of peripheral metabolism of another steroid secreted by the testis. This sort of inference has been made extensively and has been confirmed on many occasions. It should be clear however that the demonstration that a particular steroid is synthesized in vitro or in vivo from a radioactive precursor gives no information about secretion. One further caution is necessary; there are differences in the testicular secretory patterns among species so that extrapolation to man may not be warranted.

Journal ArticleDOI
01 Mar 1970-Steroids
TL;DR: The time course of response for the two stimuli specific to aldosterone production was similar to the zona fasciculata response to ACTH, and there was no obligatory increase in corticosterone secretion as a result of the mobilization of biosynthetic events leading to increase ald testosterone secretion.

Journal ArticleDOI
TL;DR: It is concluded that rhythms in food ingestion and adrenal cortical secretions play roles in the generation of the rhythmicity of hepatic tyrosine transaminase activities but that the diurnal variation in adrenal corticosterone content is not related to the cyclicity of food intake.
Abstract: Dietary intake and adrenal cortex effects on diurnal rhythm of hepatic tyrosine transaminase activity and adrenal corticosterone content in rats

Journal ArticleDOI
TL;DR: Paired male and female rats of the same age were studied in terms of their in vitro adrenal incubation with 3H-pregnenolone and it was found that, comparatively, the formation of corticosterone, androstenedione and dehydroepiandrosterone was higher in the female; testosterone was formed more in the male, while 11-betahydroxyandrostenedion production was variable.
Abstract: Paired male and female rats of the same age were studied in terms of their in vitro adrenal incubation with 3H-pregnenolone. The labeled products were isolated and measured. It was found that, comparatively, the formation of corticosterone, androstenedione and dehydroepiandrosterone was higher in the female; testosterone was formed more in the male, while 11-betahydroxyandrostenedione production was variable. The ratio of each individual C-19 steroid to corticosterone was higher in the male, and the androstenedione: testosterone ratio was always higher in the female.

Journal Article
01 Jul 1970-Surgery
TL;DR: The results suggest that the syndrome of medullary carcinoma of the thyroid gland, pheochromocytomas, and multiple neuromas may be a systemic disorder of neuroectodermal cells.

Journal ArticleDOI
21 Feb 1970-Nature
TL;DR: This possibility that the absence of growth of the adrenal cortex after hypophy-sectomy might affect catecholamine content is investigated in the present experiments in which foetal hypophysectomy in utero was carried out at 93–105 days gestation in sixteen Welsh ewes.
Abstract: DESTRUCTION of the pituitary gland of the foetal lamb in utero results in an indefinite prolongation of pregnancy1. This seems to be caused by a reduction in the secretion from the foetal adrenal cortex, for parturition can be induced in either post-mature hypophysectomized lambs or premature normal foetuses by infusions of ACTH or of large doses of cortisol into the foetus2. There is, however, a close association between the adrenal cortex and the concentration of adrenaline in the adrenal medulla3–6. In the lamb the rapid growth of the adrenal cortex immediately before birth is accompanied by a slight rise in the proportion of adrenaline in the gland7; absence of growth of the adrenal cortex after hypophy-sectomy might therefore affect catecholamine content, or more specifically the ratio of adrenaline to noradrenaline in the medulla, particularly during the period of prolonged gestation. This possibility has been investigated in the present experiments in which foetal hypophysectomy in utero was carried out at 93–105 days gestation in sixteen Welsh ewes.



Journal ArticleDOI
TL;DR: These ultrastructural findings are discussed in relation to the numerous biochemical data, suggesting that the cells of the zona glomerulosa are resting elements at birth, while the Cells of theZona fasciculata are active steroid-secreting elements already in late gestation.

Journal ArticleDOI
TL;DR: Electron micrographs of trypsin-dissociated rat adrenal showed predominantly intact rounded cells without internal damage, and the addition of adrenocorticotropic hormone to the cellular suspension for 2 hours produced corticosterone, however, these stimulated cells did not display any significant ultrastructural change.
Abstract: Electron micrographs of trypsin-dissociated rat adrenal showed predominantly intact rounded cells without internal damage The population contained cells from the glomerular, intermediary and fascicular zones with cells from the zona fasciculata predominant The presence or absence of cells from the reticular zone could not be determined Cells from the medullary zone were absent The addition of adrenocorticotropic hormone (ACTH) to the cellular suspension for 2 hours produced corticosterone However, these stimulated cells did not display any significant ultrastructural change