Adrenal Cortical Hormones Research Articles

Blood pressure vulnerability to volume contraction: regulation by adrenal cortical hormones.

Although the unique sensitivity of blood pressure to hemorrhage after adrenalectomy can be overcome by adrenocortical hormones the specificity of this steroid effect is not known. Under pentobarbital anesthesia five groups of six adult male Sprague-Dawley rats were bled into a 0.9% saline-primed pressure-balanced reservoir. A mean arterial pressure of 50 Torr was maintained for 3 h. When compared to normal rats, those with adrenalectomy showed significantly lowered bleeding volume (P less than 0.05 to less than 0.001). In untreated adrenalectomized rats 120 min following hemorrhage, saline was consistently taken up from the reservoir to maintain blood pressure at 50 Torr. Deoxycorticosterone-cortisol (intravenous bolus coupled with infusion) restored bleeding volume to normal in adrenalectomized rats. Aldosterone (constant infusion) also protected bleeding volume after adrenalectomy, P less than 0.05 to less than 0.01, but this effect was significantly less striking than that of cortisol 180 min after the onset of bleeding, P less than 0.001. Sham adrenalectomy did not affect bleeding volume. Aldosterone appears to be effective in restoring normal bleeding volume sensitivity after adrenalectomy but this effect of aldosterone is less sustained than that seen with cortisol.

Rare Occurrence of Addisonʼs Disease and Diabetes Mellitus in Children

We report on two children with both Addison's disease and diabetes mellitus, a rare occurrence in children. One of the children first developed Addison's disease and later developed diabetes mellitus, while the other had the onset of diabetes mellitus first and later Addison's disease. In the latter patient a direct relationship was shown between the insulin dose and adrenal cortical hormone. Organ-specific antibody studies are reported and the diagnosis and management of these combined endocrinopathies are discussed.

Stressor exposure and immunological response in man: Interferon-producing capacity and phagocytosis

Exposure of 8 healthy human females to a moderately stressful 77-hr vigil under strictly controlled conditions was accompanied by changes in adrenal cortical and medullary hormones compatible with a stress reaction. The ability of the lymphocytes to procedure interferon in response to the addition of Sendai virus to blood samples rose during the stressor exposure and was highest after this. Phagocytosis by peripheral blood phagocytes showed a decrease during the vigil and was followed in post-exposure samples by a rise to levels above pre-exposure values.

Lymphocyte Depletion Induced by Cholera Toxin; Relationship to Adrenal Cortical Function

Intravenous injection of cholera toxin (choleragen) into mice caused a profound lymphocytopenia associated with marked cellular depletion of the lymph nodes, spleen, and thymus. After administration of 1 mu g of choleragen, lymphocytopenia was mot marked at 24 hr; recovery occurred 6 to 10 days later. Similarly depletion of lymph nodes and spleen was maximal at 24 hr with recovery by 14 days. Choleragen also caused a marked elevation of serum corticosterone and lymphocyte depletion was not observed in adrenalectomized mice. These results suggested that the lymphocytopenic effect of choleragen was mediated by increased production and secretion of adrenal cortical hormones secondary to a rise in intracellular cAMP induced by cholera toxin. The site of action of choleragen may be the adrenal cortex itself and/or the hypothalamic-pituitary system.

Hormonal drugs.

The pharmacologic effects of the adrenal cortical hormone, cortisol, and its synthetic congeners on normal tissues can be viewed as a reallocation of the resources of the organism. Under the influence of these compounds, peripheral organs, including the skin, are systematically robbed of their constituents in an exaggerated reenactment of primitive defense reactions. Teleologically, it appears that the glucocorticoids remove materials from some tissues in an effort to preserve normal functioning in other organs. One finds wastage of lymphatic, osseous, muscular, and dermal tissues; at the same time, the liver, receiving the breakdown products of these organ systems, has an enhanced synthesis of ribonucleic acid (RNA), produces increased amounts of glucose and glycogen, and synthesizes selected enzymes of amino acid and carbohydrate metabolism at increased rates.

Triiodothyronine and hydrocortisone effects on Rana pipiens erythropoiesis

The effects of triiodothyronine and hydrocortisone individually and combined on Rana pipiens erythropoiesis have been studied in terms of their ability to stimulate hematocrit and 50Fe uptake into peripheral blood, bone marrow and spleen. The hormones individually stimulate erythropoiesis as indicated by increased isotope uptake into hemopoietic tissues and the hormones are approximately additive in terms of their ability to raise hematocrit and increase the % uptake of 50Fe into peripheral blood and spleen. These hormones have been shown to be elevated in frogs during the season when erythropoiesis is also high. Our data are consistent with the hypothesis that thyroid and adrenal cortical hormones are active in a general metabolic activity increase and thus stimulate erythropoiesis indirectly rather than by direct action on erythropoietic tissues.

Role of adrenal cortex and medulla in hypertension.

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.

Effects of adrenal cortical hormones on carbohydrate, protein, and fat metabolism

Effects of adrenal cortical hormones on carbohydrate, protein, and fat metabolism

A humoral component of the natriuretic mechanism in sustained blood volume expansion.

A natriuretic and diuretic response to whole blood infusion in the rat, exaggerated and sustained by intravenous reinfusion of excreted urine, was shown to be associated with increased glomerular filtration and reduced tubular reabsorption. Cross-circulation of animals so responding (donor rats) with isovolemic recipients led to a modest natriuretic and diuretic response in the latter, not accounted for by altered physical composition of the blood nor by observed changes in filtration rate or arterial blood pressure. The recipient natriuresis was unchanged when nephrectomized donors were used and it occurred in experiments in which donor urine was simultaneously replaced by intravenously infused Ringer-Locke solution; the natriuretic property of the cross-circulating blood could therefore not have been due to reinfusion of urinary constituents, nor to accumulation of metabolites, nor to a factor of renal origin. A recipient natriuresis was also observed when the expanded and urine reinfused donor had been acutely adrenalectomized, ruling out an altered secretion of adrenal cortical or medullary hormones as a principal cause of this natriuresis; the data, however, do not exclude participation of reduced aldosterone secretion in the normal effector mechanism. In control experiments in which whole blood was exchanged for donor blood, a small delayed natriuresis did occur in the recipient; this could be completely prevented by administration of aldosterone. In similar exchange experiments with adrenalectomized donors, a small natriuresis developed in the recipient before blood administration but declined afterwards. These minor natriuretic effects probably resulted from altered mineralocorticoid content of the cross-circulating blood due to factors other than blood volume change. The larger natriuretic response seen in all recipients when the donor was volume expanded must have been due largely to a humoral natriuretic factor of other than renal or adrenal origin.

Effect of Escherichia coli endotoxins on plasma para-phenylenediamine oxidase (caeruloplasmin) activity in the domestic fowl

The intravenous injection of pathogen-free fowls with endotoxin preparations obtained from 3 strains of Escherichia coli (02, 078 and 0111) produced a two- to five-fold increase in caeruloplasmin levels as measured by the activity of p-phenylenediamine oxidase in the plasma. This response was maximal 24 hours after the injection, was still detectable after 48 hours and was similar for the 2 doses used (1 and 3 mg./kg. body weight). One batch of the 0111 preparation produced a greater response than the other preparations which did not differ appreciably from each other in this respect. Different potency patterns were revealed by mouse toxicity experiments in which lethality and effect on body weight were measured. When preparations were injected into chicks at weekly intervals the effect of the first injection on caeruloplasmin levels was greater than the subsequent responses which did not vary significantly. It was concluded that the elevations in caeruloplasmin levels which accompany infections involving gram-negative bacteria must be at least partly due to the action of endotoxins. These may induce caeruloplasmin synthesis by promoting the release of adrenal cortical hormones. One of the functions of caeruloplasmin may be to regulate the plasma levels of catecholamines and serotonin and so minimise metabolic disturbances.

The anti-inflammatory effect of catecholamines in the peritoneal cavity and hind paw of the mouse.

1. Carrageenin or 5-hydroxytryptamine-induced oedema of the mouse hind paw was antagonized by catecholamines acting on both alpha- and beta-adrenoceptors.2. Increased permeability of the mouse peritoneum induced by the local injection of acetic acid or pro-inflammatory mediators was antagonized by catecholamines acting predominantly on beta-adrenoceptors.3. The anti-inflammatory effect of catecholamines was due neither to hyperglycaemia nor to the release of adrenal cortical hormones.

Thymolytic and adrenal cortical responses to the LDH-elevating virus.

SummaryFollowing infection of intact mice with the LDH-virus, a significant thymus involution was observed. Since there was no thymus involution in adrenalectomized mice infected with the virus, a virus-induced adrenal cortical hormone increase or activation is postulated. The observation of an increase in spleen and lymph node weight in both intact and adrenalectomized LDH-virus infected mice may result from a virus-induced proliferation of thymus-independent lymphatic tissue, which is unaffected by the adrenal cortical hormones.

Effect of Force-feeding Diets Lacking Leucine, Valine, Isoleucine, Threonine or Methionine on Amino Acid Catabolism in Rats

To investA­gate the effect of a deficiency of one amino acid on amino acid catabolism, rats were force-fed a 10% amino acid diet devoid of one or two essential amino acids. Body weight changes, urinary nitrogen, liver trypto- phan pyrrolase (L-tryptophan:oxygen oxidoreductase, EC 1.13.1.12, TPase) and tyrosine-a-ketoglutarate transaminase (L-tyrosine:2-oxoglutarate aminotransfer- ase, EC 2.6.1.5, TKase) activities, and trichloroacetic acid-soluble nitrogen of the gastrointestinal contents were measured, a) There were lower activity of TKase and delayed disappearance of dietary nitrogen from the gastrointestinal tract of rats force-fed the leucine-free diet or the diets lacking in leucine and another amino acid than in rats fed diets lacking other amino acids, b) Force-feeding valine-free diets resulted in a time lag of TPase activity-induction and delayed disappearance of dietary nitrogen from the gastrointestinal tract. These effects were not eliminated by the further omission of leucine or isoleucine from the valine-free diet, c) Acute weakness of rats fed the valine-free diet could be re tarded by the omission of leucine from this diet. These results indicated that these specific effects of leucine and valine deficiencies depend upon the difficulty in catabolism of amino acids, and that the presence of leucine or valine in a diet might play a specific role in adrenalcortical hormone secretion. J. Nutr. 101: 1647-1656, 1971.

Mode of action of adrenal cortical hormones. IV. Enhanced glucocorticoidal activity of steroids associated with decreased chemical reactivity of the 4 -3-ketone and the C-20, 21-ketol groups.

Mode of action of adrenal cortical hormones. IV. Enhanced glucocorticoidal activity of steroids associated with decreased chemical reactivity of the 4 -3-ketone and the C-20, 21-ketol groups.

A Block in Epinephrine-induced Glycogenolysis in Hearts from Adrenalectomized Rats

Abstract Perfused hearts from adrenal-deficient rats showed an impaired glycogenolytic response to suboptimal concentrations of epinephrine as judged by measurements of tissue glycogen and lactate production. The glycogenolytic response could be restored to normal by treatment of these animals with cortisol in vivo. Individual steps in the path of epinephrine-stimulated glycogenolysis were examined. Adrenalectomy did not impair adenosine 3',5'-monophosphate accumulation in response to several concentrations of epinephrine; a histone kinase, partially purified from hearts of adrenalectomized rats, was as sensitive to activation by adenosine 3',5'-monophosphate as the enzyme prepared from normal hearts; and the activation of phosphorylase b kinase by several concentrations of epinephrine was unaffected by the deficiency of adrenal cortical hormones. However, suboptimal concentrations of epinephrine did not activate phosphorylase in hearts from adrenalectomized rats to the normal extent. These findings suggest therefore that the defect following adrenalectomy lies in the activity of phosphorylase b kinase. The defect could be overcome by administration of adrenal glucocorticoid in vivo or by raising the perfusate calcium concentration.

Postural Hypotension and Steroids

To the Editor.— Earlier literature concerning the use of the adrenal cortical hormones emphasized the occasional development of adrenal crisis, secondary to the prolonged suppression of the pituitary adrenal axis many months after cessation of these steroids. The problem was resurrected in a case in connection with cyclic use of large doses of prednisone as an adjunct to chemotherapy. Report of a Case.— In a 64-year-old black American, lymphadenopathy developed in the left inguinal region in May 1970. Initial biopsies showed only reactive hyperplasia. The lymphadenopathy appeared subsequently in the axilla and supraclavicular areas, and biopsies in October showed lymphosarcoma. The blood pressure at that time was 110/70 mm Hg, but the patient was not specifically checked for postural hypotension. A general medical evaluation was otherwise unremarkable. The hemoglobin level ranged from 9.5 to 10.8 gm/100 ml. The white blood cell count was 3,200/cu mm, with a normal differential cell

Seasonal changes of pelage in the vole ( Microtus agrestis) : III. The role of the endocrine system

The action of hormones on different aspects of hair growth in the vole ( Microtus agrestis) results in a seasonal change of pelage which is correlated with the environmentally controlled activity of the endocrine system. Our evidence suggests that sex hormones act by inhibiting the activity of hair follicles without affecting the type of hair produced. Thyroxine stimulates the amount of hair secreted by the individual hair follicles and adrenal cortical hormones encourage loss of club hairs. Thus, increased secretion of these hormones in spring leads to the production of a sparse coat with coarse hairs. A lowered secretion of hormones in autumn results in a dense coat with fine hairs.

The effect of the administration of cortisol on the levels of cortisol and electrolytes in blood and cerebrospinal fluid in man

In some patients with brain tumor, neurosurgery involving ventricular drainage and ventriculography resulted in an increase in the sodium level in cerebrospinal fluid without any modification of its level in blood. In these patients, the effects of the administration of cortisol on the levels of corticosteroids, sodium, and potassium in blood and cerebrospinal fluid were studied. After the administration of cortisol, the corticosteroid levels in blood and cerebrospinal fluid were markedly increased. When patients had normal levels of sodium in cerebrospinal fluid, cortisol administration did not affect these sodium levels. However, when the sodium level in cerebrospinal fluid was high, the sodium level decreased 2 to 4 hr after the administration of cortisol. In all these patients, the sodium and potassium levels in blood were not influenced by cortisol administration. This finding may have bearing upon the apparent beneficial action of adrenal cortical hormones on cerebral edema following trauma or brain surgery.

Adrenal cortical and medullary hormones in recovery of tissues from local injury.

Adrenal cortical and medullary hormones in recovery of tissues from local injury.

On the role of antidiuretic hormone in the inhibition of acute water diuresis in adrenal insufficiency and the effects of gluco- and mineralocorticoids in reversing the inhibition.

In order to determine whether or not antidiuretic hormone (ADH) is essential to the inhibition of an acute water diuresis in adrenal insufficiency, the response to oral water loads was tested in rats with hereditary hypothalamic diabetes insipidus (DI) which lack ADH. It was found that 60 min after water loads of 3 or 5% of body weight urine flow was significantly lower and urine osmolality significantly higher in adrenalectomized DI rats than in the same DI rats before removal of their adrenal glands. The efficacy of gluco- and mineralocorticoids in reversing the inhibition was then determined in the same adrenalectomized DI rats. Prednisolone alone, administered either acutely or chronically, restored the response in urine flow to that seen in the same rats before adrenalectomy, but failed to correct the defect in urinary dilution. Aldosterone when given alone tended to correct the diluting ability but not the response in urine flow. When these two adrenal cortical hormones were given simultaneously, both the urine flow and urine osmolality were nearly identical to what they had been in the same DI rats before adrenalectomy. These studies strongly suggest (a) that ADH is not essential to the inhibition of an acute water diuresis in adrenal insufficiency, although it may abet the inhibition in individuals without diabetes insipidus, which can elaborate ADH; and (b) that both gluco- and mineralocorticoids are required in adrenal insufficiency in order to fully restore the water diuresis as judged by the dual criteria of urine flow and urine osmolality.