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Showing papers on "Adrenal cortex published in 1973"


Journal ArticleDOI
Georg Dhom1
TL;DR: The increase in adrenal weight and structural development of the cortex is studied in 630 pairs of adrenals from children between 1 and 19 years and in 22 cases a delayed adrenarche is found, bringing into relation with production of androgens.
Abstract: Summary The increase in adrenal weight and structural development of the cortex is studied in 630 pairs of adrenals from children between 1 and 19 years. In the group of cases of sudden death adrenal weight increases from 2 g in the 2nd year of life to 4 g in the 10th year. Adult values are achieved at the end of puberty. There exists a significant correlation between adrenal weight, age and body surface. A sex difference does not exist. In cerebral lesions adrenal weight at any period is highly significantly above that of the group of sudden deaths. The adrenal weights of the group of all other cases, designated as consuming diseases, occupy an intermediate position. The breakdown of the medullary capsule and the development of the zona reticularis are the outstanding features of structural development of adrenal cortex. Focal development of a zona reticularis starts at the age of 5 years, at 8 years it usually is present as a continuous zone. The juvenile reticularis cells have larger nuclei than the cells of the zona fasciculata and show a compact cytoplasm without pigment granules. No signs of increased cell destruction are seen. In stress-situations mitotic figures are found predominantly here. The development of the zona reticularis is considered to be the morphologic equivalent of adrenarche and is brought into relation with production of androgens. In 22 cases we found a delayed adrenarche. In such cases a complete medullary capsule is still found after the 5 th year of life, whereas development of the zona reticularis has not yet started after the 10th year of life. Cerebral lesions and congenital cardiac defects are present in 17 of these 22 cases. In 11 cases an accelerated adrenarche is seen, of these 8 show cerebral lesions. By the age of 3 years the medullary capsule has already disappeared completely and the zona reticularis is beginning to develop. In the majority of these cases gonadarche is disturbed too, congruity between gonadarche and adrenarche does not necessarily have to exist.

157 citations



Journal ArticleDOI
TL;DR: The authors showed that the hypothalamo-hypophyseal-adrenal axis is functional before hatching in chicks, and the pituitary becomes important in maintaining both the resting level of hormone and the stress response between days 14 and 16 of incubation.
Abstract: Basal plasma levels of corticosterone increased gradually during the second half of incubation, reaching a peak around the time of hatching. Stress resulted in a very significant elevation of corticosterone above the basal level in embryos 16 days or older, but not in younger embryos. Newly hatched chicks did not respond to stress, but a typical stress response was evident one week after hatching. Adrenocorticotropin (100 mU) elicited a significant rise in plasma corticosterone in 14-day embryos and in newly hatched chicks, demonstrating that the adrenal is capable of responding to pituitary stimulation at these times when a stress response does not occur. Decapitated 16-day embryos had significantly lower basal levels of corticosterone than normal, and showed no rise in corticosterone in response to stress. Basal levels of corticosterone were unaffected by decapitation of 14-day embryos. Grafting ten-day embryonic pituitaries to the chorioallantoic membrane on day 9 of incubation restored normal basal hormone levels on day 16 in decapitated embryos, but did not restore the ability to respond to stress. This study demonstrates that the hypothalamo-hypophyseal-adrenal axis is functional before hatching in chicks. The adrenal exhibits significant autonomous functional capability prior to day 14, and the pituitary becomes important in maintaining both the resting level of hormone and the stress response between days 14 and 16 of incubation. The hypothalamus does not appear to control normal resting levels of corticosterone, but is essential for the stress response.

120 citations



Journal ArticleDOI
TL;DR: The analysis of the adrenal steroids revealed that acute stress induced by ether anaesthesia stimulated cholesterol ester depletion in adrenal lipid droplets, and the combination of all three activators proved to be more effective than any one or combinations of any two factors.
Abstract: The cholesterol content and the activities of cholesteryl esterase and cyclic-AMP-dependent protein kinase have been studied in the adrenal glands of rats. These studies have been performed on the adrenal glands of rats injected with a protein-synthesis inhibitor, cycloheximide, and in the adrenal glands of rats exposed to ether anaesthesia to increase the blood concentration of adrenocorticotrophic hormone. The analysis of the adrenal steroids revealed that acute stress induced by ether anaesthesia stimulated cholesterol ester depletion in adrenal lipid droplets. Cycloheximide injection into rats did not significantly alter the concentrations of cholesterol and cholesterol esters in the lipid droplets. Injection of cycloheximide followed by ether anaesthesia resulted in an increase in free cholesterol with a concomitant decrease in cholesterol ester concentration within the lipid droplets. Cholesteryl esterase and protein kinase activities in rat adrenal 105000 × g supernatant fractions were significantly higher in animals subjected to stress by ether anaesthesia. Injection of cycloheximide did not prevent the stress-induced enhancement of the activities of either enzyme. Cholesteryl esterase activity was significantly enhanced by the addition of cyclic AMP, ATP and theophylline in the presence of cyclic-AMP-dependent protein kinase. The combination of all three activators proved to be more effective than any one or combinations of any two factors. The degree to which the activators stimulated cholesteryl esterase was higher in untreated animals than in animals subjected to ether anaesthesia. It is postulated that the enhancement of cholesteryl esterase activity induced by ether anaesthesia is due to the effect of adrenocorticotropic hormone on the adrenal gland, and that in vitro activation of cholesteryl esterase by cyclic AMP and ATP involves a protein-kinase-dependent phosphorylation reaction. Subcellular distribution of cholesteryl esterase activity in rat adrenal gland and some properties of the enzyme have been studied.

91 citations



Journal ArticleDOI
02 Mar 1973-Science
TL;DR: An important role for angiotensin II is suggested in the maintenance of arterial pressure by its action on specific receptor sites in arteriolar smooth muscle and in the adrenal cortex.
Abstract: An angiotensin II antagonist, [1-sarcosine, 8-alanine]-angiotensin II, was given intravenously to anesthetized dogs with thoracic caval constriction and ascites to investigate the role of angiotensin II in the control of arterial pressure. The antagonist produced a striking fall in arterial pressure and in aldosterone secretion and an accompanying increase in plasma renin activity. In a control experiment, normal anesthetized dogs were given the angiotensin analog, but it failed to reduce arterial pressure or to influence plasma renin activity. In conscious dogs with caval constriction, the antagonist produced essentially the same drop in arterial pressure as observed in anesthetized animals. These results suggest an important role for angiotensin II in the maintenance of arterial pressure by its action on specific receptor sites in arteriolar smooth muscle and in the adrenal cortex.

84 citations


Journal ArticleDOI
TL;DR: There was a marked temporal correlation between the percentage inhibition of ACTH-induced steroid production, the disruption of normal cellular structure and arrangement in the innermost zones of the adrenal cortex, and the severity of the DDD-induced mitochondria damage in the cells of the zonas fasciculata-reticularis by each of the 3 isomers of DDD.

79 citations


Journal ArticleDOI
TL;DR: It is demonstrated that plasma aldosterone concentration can be modulated acutely by transitory changes in plasma potassium concentration without a change in potassium balance.
Abstract: A B S T R A C T In studies on seven anephric patients, glucose and insulin administration before hemodialysis produced a significant reduction in plasma potassium concentration (mean reduction = 1.3, 1.7, and 1.4 meq/ liter at 60, 120, and 180 min, respectively) which was accompanied by a significant and sustained reduction in plasma aldosterone concentration. There was a significant correlation between plasma aldosterone and plasma potassium concentration (r= +0.74, P < 0.001) and between changes in the concentration of plasma aldosterone occurring in individual patients and the corresponding changes in plasma potassium concentration (r = +0.52, P < 0.01). There was no significant change in plasma sodium concentration, and plasma corticoid concentration, which was monitored as an index of ACTH elaboration, was reduced at 60 min but increased subsequently as symptoms attributable to hypoglycemia were observed. These studies demonstrate that plasma aldosterone concentration can be modulated acutely by transitory changes in plasma potassium concentration without a change in potassium balance. The effect of glucose and insulin administration on intracellular potassium in the adrenal cortex is uncertain, and although increased net movement of potassium into cells is the presumptive mechanism of the reduction in plasma potassium concentration, whether the potassium content of the adrenal cortex may have increased or decreased or remained essentially unchanged, cannot be inferred from our data.

58 citations


Journal ArticleDOI
TL;DR: Hormones which promote ageing changes or age-pathology are called “ageing hormones” and environmental influences such as stress, food supply and temperature also affect the course of ageing.

55 citations


Journal ArticleDOI
01 Nov 1973-Cancer
TL;DR: In this paper, the importance of the team approach to the problem of neoplasm of the adrenal cortex, for nowhere is there a greater necessity for the combined efforts of internists, radiologists, chemotherapists, and surgeons.
Abstract: Extensive advances in surgery of the adrenal cortex have occurred in the last 23 years. The significant historical events are outlined herein. The demonstration 22 years ago that man can survive after bilateral total adrenalectomy, with adequate substitution therapy, has given a great impetus to surgery of tumors of the adrenal. The pathology, the pathologic physiology, and important steps in preoperative evaluation and diagnosis are given in detail. The intraoperative and postoperative management are described, including the details of effective chemotherapy. Emphasis is appropriately placed on the importance of the team approach to the problem of neoplasm of the adrenal cortex, for nowhere is there a greater necessity for the combined efforts of internists, radiologists, chemotherapists, and surgeons.

Journal ArticleDOI
TL;DR: It is proposed that in the prepubertal animal at least, centripetal cell migration does occur in the z.

Journal ArticleDOI
TL;DR: Findings are interpreted as indicating that ACTH enhances the growth and the steroidogenic capacity of the adrenal zona glomerulosa, as well as of the cells, nuclei, mitochondrial fraction and membrane space, in hypophysectomized rats.
Abstract: The effects of a chronic treatment with ACTH, adenosine 3',5'-cyclic monophosphate (cyclic AMP), and N6,2'–O–dibutyryl adenosine 3',5'–cyclic monophosphate (dibutyryl cyclic AMP) on the zona glomerulosa of hypophysectomized rats have been investigated by morphometric methods and electron microscopy. It was found that ACTH completely reverses the effects of hypophysectomy on the glomerulosa cells. The structural changes involve a significant increase in the volume of the zona glomerulosa, as well as of the cells, nuclei, mitochondrial fraction and membrane space, and in the surface of smooth endoplasmic reticulum and mitochondrial cristae. Also noticeable is the hypertrophy of the Golgi apparatus and of microvilli. The lipid droplets are found to have significantly decreased. These findings are interpreted as indicating that ACTH enhances the growth and the steroidogenic capacity of the adrenal zona glomerulosa. Cyclic AMP and dibutyryl cyclic AMP are found to induce in the glomerulosal cells morphologic c...

Journal ArticleDOI
TL;DR: Experimental evidence is presented for a role of progesterone and 20alpha-hydroxypregn-4-en-3-one as inhibitors of cholesterol ester synthetase in the acute depletion of ovarian cholesterol Ester after trophic stimulation and the inhibitory effect of cyclic AMP on esterification of cholesterol with added [(14)C]-oleate.
Abstract: 1. Experimental evidence is presented for a role of progesterone and 20α-hydroxypregn-4-en-3-one as inhibitors of cholesterol ester synthetase in the acute depletion of ovarian cholesterol ester after trophic stimulation. 2. Luteinizing hormone in vitro decreased by 84% the rate of esterification of cholesterol with added [14C]oleate by slices of rabbit ovarian interstitial tissue; this effect was mimicked by cyclic AMP (adenosine 3′:5′-cyclic monophosphate) in vitro, and occurred without large changes in precursor pool sizes or membrane permeability. 3. Cyclic AMP was shown to have no direct effect on cholesterol ester synthetase or cholesterol esterase in cell-free extracts of rabbit ovarian interstitial tissue, but decreased the activity of cholesterol ester synthetase (not that of cholesterol esterase) in extracts prepared from slices previously incubated with it. 4. The inhibitory effect of cyclic AMP on esterification of cholesterol with added [14C]-oleate was prevented by both cycloheximide and aminoglutethimide phosphate (which also inhibited steroid synthesis in response to cyclic AMP). 5. Cyclic AMP raised the intracellular concentrations of progesterone and 20α-hydroxypregn-4-en-3-one in incubated slices by factors of 2.8 and 3.9 respectively. 6. Cycloheximide and aminoglutethimide phosphate administered in vivo blocked cholesterol ester depletion in response to luteinizing hormone in rats; in these ovaries cycloheximide and aminoglutethimide phosphate decreased the concentrations of progesterone and 20α-hydroxypregn-4-en-3-one and luteinizing hormone raised them. 7. Progesterone and 20α-hydroxypregn-4-en-3-one added to cell-free extracts of rabbit ovarian interstitial tissue in vitro (at concentrations comparable with those found in incubated slices) inhibited cholesterol ester synthetase by up to 85%. 8. The results are discussed with reference to the acute control of cholesterol ester concentrations in the ovary and adrenal cortex.

Journal ArticleDOI
TL;DR: Orchiectomy is often used in the management of metastatic adenocarcinoma of the prostate, an androgen dependent tumour, since it markedly reduces the concentrations of plasma testosterone and temporarily inhibits the growth of the neoplasma.
Abstract: Plasma testosterone produced mainly by the testes is considered a major factor in the stimulation of the growth of tumor tissue in carcinoma of the prostate. Therefore orchiectomy is considered the treatment of choice. However after a period of time tumor growth recommences but can be delayed by the administration of estrogens or compounds with antiandrogenic activity. Study was made of 27 patients with prostatic adenocarcinoma aged 37 to 74 years who had orchiectomy to determine whether circulating androgens of either adrenal or extraglandular origin might be present. They were not given hormone therapy. The assay 17-ketosteroids (17KS) and 17-hydroxycorticosteroids (17-OHCS) in 24-hour urine specimens and the assay of testosterone and androstenedione in blood were done on samples collected before and 10 30 and 60 days after operation. Details of technique are given. Before orchiectomy test results were within normal limits. In 17 patients marked reduction of plasma testosterone was found; these men benefitted from the operation. In 10 patients plasma testosterone and androstenedione remained 5 times higher than in the others and the operation did not improve symptoms. The adrenal cortex is considered the source of the product of androgens in these patients. Suppression of adrenal function with dexamethasone was done. A drop in testosterone and androstenedione levels was observed. In orchiectomized patients the adrenal cortex appears to be the source of testosterone and other weaker androgens. The prostatic adenocarcinoma tissue may be capable of transforming weak endrogens into more active compounds.

Journal ArticleDOI
TL;DR: The results implicate an important role for protein kinase in ACTH action on the adrenocortical cell, and some low doses of ACTH that elicited a marked (but submaximal) steroidogenic response failed to cause a clear stimulation ofprotein kinase activity in isolated adrenal cells.
Abstract: A method has been developed for investigation of the effect of adrenocorticotrophic hormone (ACTH) on the state of activation of a cyclic AMP-dependent protein kinase within cells of the adrenal cortex. Enzyme activity was measured in terms of the quantity of (32)P transferred from [gamma-(32)P]ATP to histone under conditions in which bound cyclic AMP did not dissociate from the regulatory subunit of the protein kinase ACTH (1x10(-2)i.u./ml) caused a rapid and complete activation of the cyclic AMP-dependent protein kinase activity within 2min of hormone addition to the isolated cells. In response to a range of ACTH concentrations a sigmoid log dose-response curve for protein kinase activation was obtained, with half-maximal stimulation attained at about 1x10(-3)i.u./ml. However, some low doses of ACTH that elicited a marked (but submaximal) steroidogenic response failed to cause a clear stimulation of protein kinase activity in isolated adrenal cells. Theophylline (2mm) potentiated the effect of ACTH on protein kinase activity. The results implicate an important role for protein kinase in ACTH action on the adrenocortical cell.

Journal ArticleDOI
TL;DR: This paper illustrates how a membrane protein which requires detergents for its solubilization can be characterized and measured by immunological methods.
Abstract: — Rabbits were immunized with chromomembrin B, i.e. a membrane protein isolated from chromaffin granules of bovine adrenal medulla. When the rabbit sera were tested by immunodiffusion in the presence of various detergents, only negative results were obtained, whereas with complement fixation antibodies could be demonstrated. With this method the subcellular distribution of chromomembrin B in bovine adrenal medulla was determined. The results demonstrate that this protein is specifically localized in the membranes of chromaffin granules. In the mitochondrial and microsomal fractions it is present only in small amounts which are attributable to a contamination of these fractions with chromaffin granules. The subcellular distribution of chromomembrin R in bovine splenic nerves indicates that this antigen is also found in the membranes of noradrenalinestoring vesicles of sympathetic nerve. Chromomembrin B or a related antigen was detected in chromaffin grades isolated from pig and rat adrenal and in those isolated from a human phaeochromocytoma. It is also present in total membranes obtained from posterior and anterior hypophysis, but it is absent from membranes isolated from parotid gland, liver and adrenal cortex. This paper illustrates how a membrane protein which requires detergents for its solubilization can be characterized and measured by immunological methods.

Journal ArticleDOI
30 Mar 1973-Science
TL;DR: Cells from the adrenals of hypophysectomized rats (up to 28 days after operation) require less adrenocorticotropic hormone to induce one-half maximal rate of production of 3',5'-adenosine monophosphate than do cells from the Adrenals of intact rats.
Abstract: Cells from the adrenals of hypophysectomized rats (up to 28 days after operation) require less adrenocorticotropic hormone to induce one-half maximal rate of production of 39,59-adenosine monophosphate than do cells from the adrenals of intact rats. A corresponding increase in sensitivity is reflected in the steroidogenic response to adrenocorticotropic hormone up to 2 days after hypophysectomy.

Journal ArticleDOI
TL;DR: Cytoplasmic inclusions similar to spironolactone bodies can be detected in other organs after the administration of various compounds and can be regarded as neither specific to sp ironolact one treatment nor exclusively inducible in the zona glomerulosa of the adrenal cortex.
Abstract: Numerous spironolactone bodies have been detected in the zona glomerulosa cells of the adrenal cortex of a 36-year-old spironolactone-treated woman whose non-tumorous right adrenal gland was removed surgically because of primary hyperaldosteronism. Electron microscopy revealed spherical laminated whorls which consisted of a central core composed of an amorphous electron-dense material surrounded by numerous smooth-walled concentric membranes. Continuous with and deriving from the endoplasmic reticulum, they were present in viable cells and were not associated with ultrastructural features indicating cellular injury. Cytoplasmic inclusions similar to spironolactone bodies can be detected in other organs after the administration of various compounds. Thus, they can be regarded as neither specific to spironolactone treatment nor exclusively inducible in the zona glomerulosa of the adrenal cortex.

Journal ArticleDOI
TL;DR: The combination of inappropriate aldosterone levels and suppressed renin is diagnostic of PA; however, hypertension with low plasma renin per se is usually due to a type of essential hypertension rather than hyperaldosteronism.
Abstract: Aldosterone, the most potent mineralocorticoid known in man, is regulated by complex, multiple control systems. The major system appears to be renin-angiotensin, which responds to changes in extracellular volume and sodium balance. In normal man or when the renin system is suppressed as in primary aldosteronism, potassium can directly alter adrenal aldosterone secretion. ACTH, at least acutely, has a similar but less specific effect on the adrenal cortex than angiotensin II. Other control factors may also be operative, but their existence is suggested only by indirect studies. The absence of aldosterone binding in blood leads to a short chemical half-life, a high metabolic clearance (1600 liters/day), and hepatic extraction, and its lack of activity by mouth. Although much was learned about this hormone by measuring excretion rates in urine of metabolites, the measurement of blood levels and blood production rates are more representative of the hormone level reaching target tissues. Control of diet, posture, and time of day is necessary for interpretation. The clinical description of patients with primary aldosteronism remains similar to Conn's original report. Milder expressions of the disorder are now detected and neuromuscular symptoms are uncommon. Hypertension and hypokalemia with inappropriate kaliuresis remain the hallmarks of the disease. Normokalemia appears to be a rare variant as long as there is adequate dietary sodium and no technical or sampling errors. Except for the electrolyte acid-base disorder, primary aldosteronism is usually indistinguishable clinically from essential hypertension. Most PA patients will have unexplained frontal headaches and nocturia. Although there are many physiologic abnormalities, the key diagnostic test is the use of exogenous mineralocorticoid. Fludrocortisone (9α-fluorohydrocortisone) 0.6 mg/day × 3 orally will minimally suppress plasma or urinary aldosterone, while normals or patients with other types of hypertension will show marked suppression. Spironolactone will reverse the electrolyte abnormalities and usually improve the hypertension, although the latter effect is seen in lowrenin hypertension and is nonspecific for PA. Adrenal venography with adrenal vein measurements is very helpful in localization and distinguishing adenoma from bilateral hyperplasia. PA due to adenoma is generally treated surgically, while hyperplasia is currently thought to be best managed medically, since the hypertension is not reversed by adrenalectomy. The combination of inappropriate aldosterone levels and suppressed renin is diagnostic of PA; however, hypertension with low plasma renin per se is usually due to a type of essential hypertension rather than hyperaldosteronism.

Journal ArticleDOI
TL;DR: The present study indicates that although the adrenal cortex can extrude cyclic AMP in response to ACTH, the gland probably contributes minimally to the extracellular cyclicAMP pool in rats under physiological conditions.
Abstract: The effects of ACTH on cyclic AMP levels in peripheral and adrenal vein plasma as well as in adrenal tissue were studied in the hypophysectomized rat and correlated with the steroidogenic response. High doses of ACTH increased adrenal tissue cyclic AMP levels and also markedly elevated cyclic AMP in adrenal vein and peripheral plasma. The gradient between adrenal vein and peripheral plasma cyclic AMP following ACTH was comparable to that observed for corticosterone. Small doses of ACTH produced a maximal rate of steroidogenesis and a several fold elevation in adrenal tissue cyclic AMP, but produced only a slight change in adrenal vein plasma cyclic AMP and no detectable change in peripheral plasma cyclic AMP. The present study indicates that although the adrenal cortex can extrude cyclic AMP in response to ACTH, the gland probably contributes minimally to the extracellular cyclic AMP pool in rats under physiological conditions. (Endocrinology 92: 1502, 1973)

Journal Article
TL;DR: Primary ultrastructural changes in the mitochondria and other organelles in zona glomerulosa cells of the adrenal cortex were noted in rats maintained for up to 8 days on a potassium-enriched or a sodium-deficient diet, probably related to the persistent increased active steroid synthesis.
Abstract: Ultrastructural changes in the mitochondria and other organelles in zona glomerulosa cells of the adrenal cortex were noted in rats maintained for up to 8 days on a potassium-enriched or a sodium-deficient diet. In both groups of animals, aldosterone production is known to be increased. Principal ultrastructural changes in the rats maintained on a potassium-supplemented or a sodium-deficient diet consisted of a loss of electron density of the mitochondrial matrix and a change from plate-like cristae to tubular-vesicular cristae. These changes were similar in both potassium-enriched and sodium-depleted animals after 8 days and were markedly different from control animals. Morphologic changes occurred after the initial increase in aldosterone production, which has been measured in 1 to 2 days in both sodium-depleted and potassium-enriched rats. The mitochondrial changes described are probably related to the persistent increased active steroid synthesis.

Journal ArticleDOI
TL;DR: Quantitatively, oxidation at C-11 to cortisone was the major biotransformation which occurred in all tissues studied, and the capacity to sulfate cortisol was noticed in the adrenal, liver, kidney, muscle and lung.

Journal ArticleDOI
TL;DR: Aldosterone is a highly important mineralocorticoid produced in the zona glomerulosa of the adrenal cortex in response to angiotensin II, potassium ions, and adrenocortiotropic hormone.
Abstract: Aldosterone is a highly important mineralocorticoid produced in the zona glomerulosa of the adrenal cortex in response to angiotensin II, potassium ions, and adrenocorticotropic hormone. Its most important physiological functions concern maintenance of sodium balance, potassium homeostasis, and excretion of hydrogen ions. Although the distal tubule of the kidney appears to be its principal site of action, its effects on other membranes and glandular tissues may induce secondary effects on other portions of the nephron. Its precise mechanism of action is the result of its reaction with highly specific protein receptors located only in responsive tissues. These proteins, in complex with aldosterone, stimulate formation of DNA-dependent RNA that in turn leads to synthesis of new proteins. The latter, by an unknown mechanism, are responsible for the definitive action of aldosterone.

Journal ArticleDOI
TL;DR: It is indicated that normal levels of aldosterone secretion can be maintained in the absence of the renin-angiotensin system and the pituitary secretion of adrenocorticotropic hormone and hemorrhage will greatly enhance ald testosterone secretion in the presence of the head and the kidneys but only if the serum potassium concentration is allowed to rise following the hemorrhage.
Abstract: In eight intact, anesthetized dogs the aldosterone secretory rate averaged 13.8 ± 1.9 ng/min (mean ± SE). One hour after nephrectomy and decapitation, the aldosterone secretory rate decreased to 2.3 ± 1.7 ng/min and failed to increase in response to hemorrhage. By 8 hours after surgery, the aldosterone secretory rate had returned to control levels. The serum potassium concentration gradually increased from 3.2 ± 0.5 mEq/liter in the control samples to 5.3 ± 0.5 mEq/liter in the 8-hour samples. Eight hours after nephrectomy and decapitation, the arterial blood pressure was lowered to 70 mm Hg by hemorrhage in six dogs. During the next 3 hours, the aldosterone secretory rate increased from 11.2 ± 2.1 ng/min to 27.3 ± 2.1 ng/min. Associated with the increase in the aldosterone secretory rate following hemorrhage was a further increase in the serum potassium concentration from 5.3 ± 0.5 mEq/liter to 6.8 ± 0.5 mEq/liter. The aldosterone secretory rate did not increase following hemorrhage when the rise in serum potassium concentration was prevented by hemodialysis. These data indicate that normal levels of aldosterone secretion can be maintained in the absence of the renin-angiotensin system and the pituitary secretion of adrenocorticotropic hormone. Also, hemorrhage will greatly enhance aldosterone secretion in the absence of the head and the kidneys but only if the serum potassium concentration is allowed to rise following the hemorrhage.

Journal ArticleDOI
24 Jan 1973-Nature
TL;DR: The hypertension in rats was genetical and developed spontaneously and blood pressures of all SHR rats increased and systolic blood pressure was approximately 150 mm Hg at 8 weeks and approximately 200 mm HG at 15 weeks old.
Abstract: SPONTANEOUSLY hypertensive rats (Okamoto-Aoki) (SHR) became normotensive following bilateral adrenalectomy1. In adrenalectomized SHR, hypertension was restored by the administration of adrenal cortical hormones2,3. Other reports confirmed that adrenal cortical hormones may play a principal role in the development and maintenance of hypertension4–9; increased catecholamine content10, tyrosine hydroxylase and dopamine-β-hydroxylase11 in adrenal medulla in the hypertension have also been demonstrated. The hypertension in rats was genetical and developed spontaneously. Blood pressures of all SHR rats increased and systolic blood pressure was approximately 150 mm Hg at 8 weeks and approximately 200 mm Hg at 15 weeks old.

Book ChapterDOI
01 Jan 1973
TL;DR: Two main lines of evidence have contributed to the present understanding of the regulation of tyrosine hydroxylase activity in the adrenal medulla by showing that the injection of dibutyryl cyclic AMP restores the activity of tyosine hydoxylase in hypophysectomized animals.
Abstract: Two main lines of evidence have contributed to our present understanding of the regulation of tyrosine hydroxylase activity in the adrenal medulla. One was provided by Axelrod (1971) by showing that tyrosine hydroxylase activity is regulated transynaptically, the other by Kvetnansky and collaborators (1971) by showing that the injection of dibutyryl cyclic AMP restores the activity of tyrosine hydroxylase in hypophysectomized animals.

Journal ArticleDOI
TL;DR: Findings in organotypic cultures of adrenal glands derived from 19-day-old rat embryos are at odds with commonly held notions on the morphological and functional zonation of the adrenal cortex.
Abstract: The relationship between mitochondrial ultrastructure and aldosterone production was studied in organotypic cultures of adrenal glands derived from 19-day-old rat embryos. ACTH induced transformation of mitochondrial cristae from a tubular to a vesicular configuration, and simultaneously caused a 10-fold rise in both aldosterone and corticosterone production compared with control cultures. These findings are at odds with commonly held notions on the morphological and functional zonation of the adrenal cortex. (Endocrinology 93: 1104, 1973)

Journal ArticleDOI
TL;DR: Recent studies have demonstrated that TPNH and the flavoprotein are dispensable and that the electrons for 11/3-hydroxylation can be supplied by reduced ISP, and the electron transport scheme and the oxidation-reduction properties found in previous work are outlined.
Abstract: The reconstituted steroid 1 lp-hydroxylase is a particularly suitable system for studying the individual reactions involved in hydroxylations catalyzed by mixedfunction oxidase. This system is that described elsewhere by our laboratory and is composed of a specific flavoprotein (Fp), an iron-sulfur protein (ISP), and a partially purified heme protein P-450 preparation.’ The electron transport scheme and the oxidation-reduction properties found in our previous work are outlined in FIGURE 1. These studies furthermore have demonstrated that TPNH and the flavoprotein are dispensable and that the electrons for 11/3-hydroxylation can be supplied by reduced ISP.’*8 In this paper we wish to describe in some detail the results of recent studies on the properties of the individual components of this system.

Journal ArticleDOI
28 Mar 1973-Nature
TL;DR: No detailed information is available on the subcellular distribution of steroids in the cells of the adrenal cortex, although the localization of the enzymes involved in their synthesis is well known.
Abstract: NO detailed information is available on the subcellular distribution of steroids in the cells of the adrenal cortex, although the localization of the enzymes involved in their synthesis is well known.