Showing papers on "Adrenal cortex published in 1984"

Stress hormones: Their interaction and regulation.

Abstract: Stress stimulates several adaptive hormonal responses. Prominent among these responses are the secretion of catecholamines from the adrenal medulla, corticosteroids from the adrenal cortex, and adrenocorticotropin from the anterior pituitary. A number of complex interactions are involved in the regulation of these hormones. Glucocorticoids regulate catecholamine biosynthesis in the adrenal medulla and catecholamines stimulate adrenocorticotropin release from the anterior pituitary. In addition, other hormones, including corticotropin-releasing factor, vasoactive intestinal peptide, and arginine vasopressin stimulate while the corticosteroids and somatostatin inhibit adrenocorticotropin secretion. Together these agents appear to determine the complex physiologic responses to a variety of stressors.

Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response

Abstract: The hippocampus is the principal target site in the brain for adrenocortical steroids, as it has the highest concentration of receptor sites for glucocorticoids. The aged rat has a specific deficit in hippocampal glucocorticoid receptors, owing in large part to a loss of corticoid-sensitive neurons. This deficit may be the cause for the failure of aged rats to terminate corticosterone secretion at the end of stress, because extensive lesion and electrical stimulation studies have shown that the hippocampus exerts an inhibitory influence over adrenocortical activity and participates in glucocorticoid feedback. We have studied whether it is the loss of hippocampal neurons or of hippocampal glucocorticoid receptors in the aged rat that contributes most to this syndrome of corticosterone hypersecretion. To do this, we used two model systems for producing reversible glucocorticoid receptor depletion in the hippocampus, and we found that depletion of receptors without inducing cell loss results in corticosterone hypersecretion. Furthermore, correction of the receptor deficit results in normalization of corticosterone secretion. These results focus attention on the hippocampus as an important glucocorticoid sensor in relation to the stress response. They also provide important new physiological correlates for the remarkable plasticity of the hippocampal glucocorticoid receptor system, which is under independent control by corticosterone and by vasopressin.

Stress and adrenal function.

Abstract: The natural environment is composed of various potentially hostile stressors. It is a basic requirement of life that the cells of an organism must be maintained within closely defined physiological limits. The maintenance of a constant interior mileu results from physiological and behavioural homeostatic adaptations. The physiological regulation of homeostatis is achieved by complex endocrine interactions, principally by the hormones secreted from the adrenal glands. In this brief review the responses of the avian adrenal glands to stressful stimuli, the mechanism of adrenal activation, and the function of the adrenal responses will be considered.

The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80: macrophages of endocrine organs

Abstract: Macrophages of endocrine organs have been identified by immunohistochemical localization of the macrophage-specific antigen F4/80. F4/80+ cells line vascular sinuses and capillaries in anterior and posterior pituitary, adrenal cortex, corpus luteum, parathyroid, pineal gland, and islets of Langerhans. In testis approximately 20% of interstitial cells are F4/80+. F4/80+ cells infiltrate corpus luteum in increased numbers during luteolysis.

Neuropeptide tyrosine (NPY) immunoreactivity in norepinephrine-containing cells and nerves of the mammalian adrenal gland.

Abstract: The application of immunocytochemistry at both light and electron microscopic levels has revealed neuropeptide tyrosine (NPY)-immunoreactive material to be localized to norepinephrine-containing endocrine cells Tn the adrenal medulla and also to varicose nerve fibers penetrating the adrenal cortex of several mammalian species, including horse, cat, rat, guinea pig and mouse. Correlative electron microscopic immunostaining has revealed that enkephalin and NPY immunoreactivities are co-localized to the same norepinephrine-containing secretory granules. High concentrations of NPY have been extracted from the mouse adrenal gland (1243.7 ± 122.8 pmol NPY/g wet tissue; mean ± SE). Chromatographic analysis has shown the extracted material to correspond with pure natural NPY.

Effects of Etomidate on Hormonal Responses to Surgical Stress

Abstract: The hormonal responses to surgical stress were examined in 10 patients scheduled for elective gynecologic laparotomy. Anesthesia was induced with either thiopental, 4 mg/kg, or etomidate, 0.35 mg/kg, and maintained with nitrous oxide and enflurane. Plasma cortisol, aldosterone, ACTH, and catecholamines were measured during the 24 h after the induction of anesthesia. The catecholamine responses of the patients whose anesthesia was induced with either drug were similar. The plasma ACTH concentrations for the etomidate group were greater than baseline values and the concentrations in the thiopental group (P less than 0.05) in the fourth and fifth hours. In the patients receiving thiopental, both cortisol and aldosterone concentrations were greater than the baseline value (P less than 0.05) in the second to fourth hours after induction. In the etomidate group, the plasma concentrations of cortisol were less than baseline values (P less than 0.05) in the first and second hours after induction of anesthesia and both cortisol and aldosterone were lower than those in the thiopental group (P less than 0.05) in the half to fourth hours after induction. These results confirm an earlier report of the suppression of cortisol after etomidate administration and, because aldosterone also was suppressed, suggests that etomidate exerts its effect by inhibiting early stages of steroidogenesis in the adrenal cortex.

The distribution of vasoactive intestinal peptide in the rat adrenal cortex and medulla

Abstract: There is increasing evidence for the role of the autonomic nervous system in the control of adrenal cortical function although the nature of the innervation is as yet unknown. In view of our expanding knowledge of the roles which peptidergic putative transmitters play in the autonomic nervous system, the present study was adrenal gland. Using immunocytochemical methods, VIP was found distributed in fibers in the adrenal cortex and medulla. VIP fibers were found primarily in the capsule and zona glomerulosa of the cortex and in small bundles in the medulla and appeared to innervate the parenchymal cells in both cases. Both colchicine pretreatment and ligation of the splanchnic nerve resulted in an increase in staining of fibers of the cortex and the medulla. Demedullated adrenals (regenerated) exhibited a reduced number of VIP fibers in the zona glomerulosa. It appears that the medullary and at least part of the cortical VIP fibers originate in the medullary VIP cell bodies which are regulated by the splanchnic nerve. The distribution of VIP suggests an important role for this peptide in both adrenal cortical and medullary function and a possible medullary modulation of adrenal cortical function.

Adrenal suppression following extradural steroids

Abstract: Summary Adrenocortical function was tested in 12 patients following a single lumbar extradural injection ofmethyl-prednisolone acetate (‘Depo-Medrol’) 80 mg as treatment for chronic sciatica. There was no absorption of the corticosteroid into the systemic circulation, but marked suppression of plasma Cortisol levels was documented for up to 3 weeks following the injection and the capacity of the adrenal cortex to secrete Cortisol in response to synthetic adrenocorticotrophin (ACTH) was diminished. These results suggest that the dose and frequency of extradural steroid administration should be kept to a minimum to prevent suppression of the hypothalamicjpituitaryladrenocortical axis and that patients thus treated should he considered candidates for steroid cover during surgery and other stressful procedures.

Tissue distribution and molecular forms of a novel pituitary protein in the rat

Abstract: A sensitive and specific radioimmunoassay (RIA) was developed for a novel pituitary protein that we recently isolated from human and porcine pituitary gland and designated 7B2. By employing this RIA, we were able to detect and assay this novel protein in different rat tissue extracts. The concentrations of 7B2 in rat anterior pituitary lobe, neurointermediate lobe, hypothalamus, adrenal medulla and thyroid gland were 10,400 +/- 804; 6,190 +/- 908; 773 +/- 50; 697 +/- 83 and 1,368 +/- 116 pg/mg tissue (wet weight, n = 10, mean +/- SEM), respectively. However, the concentrations of 7B2 were lower than 30 pg/mg tissue in extracts of pancreas, ileum and colon, and were below the sensitivity of the RIA in extracts of liver, kidney, spleen, lung, adrenal cortex and testis. Gel permeation chromatography of extracts of anterior pituitary lobe, neurointermediate lobe, hypothalamus, adrenal medulla and thyroid gland on Sephadex G-100 revealed that most of the immunoreactive (Ir)-7B2 has an apparent molecular weight of 45,000-50,000. Subsequent dissociation of this Ir-7B2 by polyacrylamide gel electrophoresis containing sodium dodecyl sulfate (SDS) yielded an Ir-7B2 with an apparent molecular weight of around 19,000. In addition, high K+ concentration (50 mM) induced the release of Ir-7B2 from cultured cells of both rat anterior pituitary and neurointermediate lobe. Finally, Ir-7B2 was detected in the neurosecretory granule fraction prepared from porcine neurointermediate lobe. These results indicate that 7B2 may be a novel secretory protein in the pituitary gland.

Prolactin Has a Direct Effect on Adrenal Androgen Secretion

Abstract: The role of PRL in the secretion of androgens by the adrenal glands was investigated in vivo and in vitro. In women with hyperprolactinemia whose pituitary-adrenal function was normal, there was significant correlation between serum PRL and dehydroepiandrosterone sulfate [(DHEA-S) gamma = 0.48, P less than 0.05, n = 34] and DHEA (gamma = 0.50, P less than 0.05, n = 34), but not with androstenedione. Long term administration of sulpiride to normal women increased both serum PRL and DHEA-S, whereas acute elevation of PRL after a single iv dose of domperidone had no influence on the serum DHEA-S levels. Monolayer cultures of human adrenal cells were used in order to study the direct effect of PRL on adrenal androgen secretion. The daily secretion of DHEA-S, DHEA, androstenedione, and cortisol was determined. In the absence of ACTH, PRL had no effect on steroid secretion in a 7-day culture period. In the presence of ACTH, there was a daily increase in the secretion of steroids. PRL, when added in combination with ACTH, potentiated the effect of ACTH on DHEA-S and DHEA but not on androstenedione and cortisol secretion on the seventh day in culture. These results indicate that PRL has a direct synergistic effect with ACTH on adrenal cells to increase adrenal androgen release. Increases in DHEA-S and DHEA but not androstenedione in vitro and correlation between serum PRL and DHEA-S and DHEA but not androstenedione in women with hyperprolactinemia suggest that the synergistic effect of PRL on adrenal androgen secretion may result from partial inhibition of adrenal 3 beta-hydroxysteroid dehydrogenase.

Pituitary and adrenal function in epileptic patients

Abstract: ACTH and cortisol were measured simultaneously in plasma samples obtained every 5 min from subjects at two different diurnal times. In the first study adrenocorticotropic hormone (ACTH) mean concentration and secretory rate were elevated in anticonvulsant drug-treated temporal lobe epileptic patients in comparison to anticonvulsant drug-treated patients with pseudoseizures. Cortisol mean concentrations and secretory rate were similar in these groups of subjects. In the second study, mean ACTH concentration and secretory rate were higher in temporal lobe epileptic patients than in normal controls. Both measures of ACTH secretion were similar in post-temporal lobectomy patients and normal controls. Mean cortisol concentration and secretory rates were highest in the temporal lobe epileptic patients, lowest in normal controls, and intermediate in post-temporal lobectomy patients. We conclude that ACTH and cortisol secretion is abnormal in temporal lobe epileptic patients. Temporal lobectomy restores abnormal ACTH secretion to normal whether or not seizures are controlled. The absence of ACTH changes in the pseudoseizure patients suggests that these changes are not drug induced. Cortisol secretion is similar in temporal lobe epileptic patients and pseudoseizure patients, suggesting a direct effect of the drugs upon the adrenal cortex.

Serum Dehydroepiandrosterone Sulfate in Cushing's Syndrome

Abstract: Serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) were measured in patients with hyperadrenocorticism. When compared to normal subjects of corresponding age, serum DHEA-S levels were normal or elevated in 37 patients with Cushing's disease. In contrast, DHEA-S levels were significantly lower than those of normal subjects in all 28 patients with hyperadrenocorticism due to benign adrenocortical adenoma, suggesting that ACTH is the major determinant of DHEA-S secretion and that determination of serum DHEA-S concentrations is useful in the biochemical differential diagnosis of the etiology of Cushing's syndrome. In six patients with adrenocortical adenoma, the recovery of suppressed DHEA-S secretion after removal of the adrenal gland affected by a tumor was studied. Serum cortisol levels normalized by the end of the second year after unilateral adrenalectomy, while DHEA-S levels remained low for at least 2 succeeding yr. The results suggest that deficient ACTH secretion may result in a greater and longer lasting loss in the ability of the adrenal cortex to secrete androgens than in the ability to secrete cortisol.

Adrenocortical suppression by a single induction dose of etomidate

Abstract: In a prospective controlled trial we studied the effect of a single induction dose of etomidate or thiopentone on the adrenocortical function in 29 patients undergoing elective surgery. During anesthesia and in the recovery period serum cortisol rose significantly in the thiopentone group only. In contrast, after induction with etomidate serum cortisol decreased and remained below the starting values throughout the study period (5 h). The differences between the two groups were significant at 120, 150, 180, 210, and 240 min after induction (p<0.05). Moreover, plasma ACTH increased significantly more after etomidate than after thiopentone (p<0.02) indicating relative unresponsiveness of the adrenal cortex to stimulation by endogenous ACTH. We conclude that a single i.v. bolus of etomidate (0.26 mg/kg) leads to significant adrenal insufficiency in patients without preexisting endocrine abnormalities.

Mechanisms of adrenocortical depression during Escherichia coli shock.

Abstract: • The response of the adrenal cortex to corticotropin during sepsis is variable. We have previously demonstrated a significant decrease of corticosterone production by rat adrenocortical cells in response to corticotropin stimulation after incubation with septic shock plasma (SP) as compared with control plasma (CP). We have studied the mechanisms of this depression. The following defects were demonstrated. (1) Cells bound less radioiodinated corticotropin analog after SP treatment (2.9±0.4 femtomoles/50 μg DNA) than after CP treatment (6.4±0.3 fmole/50 μg DNA). (2) Cyclic adenosine monophosphate (cAMP) production was less after SP treatment (59.3 ± 4 pmole per 10 5 cells per two hours) compared with CP treatment (110.3±11.3 pmole per 10 5 cells per two hours). (3) Exogenously added dibutyryl cAMP was unable to correct the defect in corticosterone production after SP treatment (4.96±0.7 μg/24 hr) as compared with CP treatment (6.99±0.5 μg/24 hr). Our studies suggest this defect is located in the synthesis of pregnenolone from cholesterol. These mechanisms may be responsible for the low cortisol levels previously observed in humans during septic shock. ( Arch Surg 1984;119:145-150).

Glucocorticoids and catecholamines as mediators of acute-phase proteins, especially rat alpha-macrofoetoprotein.

Abstract: Adrenal hormones were studied as possible triggering substances of the synthesis of acute-phase reactants in rats. alpha-Macrofoetoprotein, which rises sharply in concentration during inflammation, was used to monitor the acute-phase reaction. In normal rats glucocorticoids and catecholamines induce alpha-macrofoetoprotein synthesis; glucocorticoids only increase alpha-macrofoetoprotein to moderate levels in plasma, but catecholamines enhance alpha-macrofoetoprotein synthesis to very high levels, comparable with those observed in the post-injury phase. However, catecholamines in vivo also activate the adrenal cortex, suggesting a synergistic effect of both kinds of adrenal hormones. Our study showed that in adrenalectomized rats, the effect of catecholamines on alpha-macrofoetoprotein synthesis is greatly diminished, whereas the moderate effect of glucocorticoids remains. Combination of glucocorticoids and catecholamines induces extremely high alpha-macrofoetoprotein levels in both adrenalectomized and normal rats. With crossed immunoelectrophoresis it was shown that other acute-phase reactants, such as haptoglobin and alpha 1-major acute-phase protein, are affected differently by the hormones. Contrary to glucocorticoids, catecholamines give a pattern comparable with that found after surgical injury.

Aldosterone-Producing Adrenocortical Carcinoma: Preoperative Recognition and Course in Three Cases

Abstract: Three patients with primary aldosteronism due to adrenocortical carcinoma were studied, two with hyperaldosteronism alone and one also with hypercortisolism; in the later stages all three had hypersecretion of glucocorticoid and androgenic hormones. Although clinical presentations were similar to those of patients with benign adenoma, all had significantly higher concentrations of deoxycorticosterone and aldosterone and more profound hypokalemia. Stimulation with adrenocorticotropin in two patients showed a good cortisol response but no aldosterone response. The circadian rhythm for cortisol was normal but absent for aldosterone and deoxycorticosterone. Sequential 24-hour circadian studies in one patient showed that as the disease progressed, corticosterone and finally cortisol lost their circadian rhythms. Treatment with spironolactone, mitotane, or aminoglutethimide had transient clinical effects. The patients died 2 to 13 years later.

Organ and cellular distribution of inhaled metallic mercury in the rat and Marmoset monkey (Callithrix jacchus): influence of ethyl alcohol pretreatment.

Abstract: Distribution of inhaled radioactive metallic mercury vapour (203Hg0) in rats and Marmoset monkeys (Callithrix jacchus), with or without pretreatment by ethyl alcohol or aminotriazole (rat), was studied by means of whole-body autoradiography, microautoradiography and scintillation counting of excised organs. Metallic mercury is oxidized by the catalase-H2O2 complex (Complex I) to the ionic form (Hg2+) and is known to be accumulated and retained in organs such as lungs, liver, myocardium, and brain, apparently after local oxidation in these organs. To this list of organs can be added the whole respiratory tract (nasal mucosa, trachea, and bronchi), a number of endocrine organs such as adrenal cortex, thyroid, corpora lutea of the ovaries, and interstitial tissues of the testes, the uvea and retina of the eye, and the salivary glands. In the liver, a regionalized pattern of distribution corresponding to the periportal hepatocytes was observed. Similarly, the subcapsular parts of the adrenal cortex (mainly the zona glomerulosa) were responsible for most of the adrenal mercury oxidation and retention. These organs (liver, adrenal) thus have a reserve capacity to oxidize Hg°. This is apparent also by the fact that ethyl alcohol and aminotriazole (known catalase inhibitors) — which depress oxidation and retention in most organs and whole body and thus increase blood concentrations of Hg°— cause an increased retention in most liver and adrenal cells.

An immunohistochemical study of pheochromocytomas.

Abstract: Twenty -six adrenal pheochromocytomas and four normal adrenal medullae were studied immunohistochemically. These included four malignant tumors with proven metastases, six tumors in patients with neurofibromatosis, nine tumors in patients with multiple endocrine neoplasia type 2, and seven sporadic nonfamilial pheochromocytomas. Immunohistochemical localization of neuron-specific enolase (NSE) was seen in all tumors and in the four normal adrenals. Methionine enkephalin-like immunoreactivity was present in tumors from all four groups and in the normal adrenals. Corticotropinlike immunoreactivity was found focally in two normal adrenal medullae and in four benign pheochromocytomas. Our results indicated that NSE was present in all four major groups of pheochromocytomas, including benign and malignant tumors. This marker aided in distinguishing between adrenal cortical and medullary tumors in unusually difficult cases, since all normal adrenal cortex and adrenal cortical tumors had negative test results for NSE.

Early and late pathologic changes in the adrenal glands of mice after infection with herpes simplex virus type 1.

Abstract: Intranasal infection of CH/HeN mice with herpes simplex virus Type 1 (HSV-1), VR3 strain, caused a high death rate in the 3-12 days following inoculation. Acute interstitial pneumonia and focal adrenal necrosis developed in almost all the animals. About 20% of the mice showed meningoencephalitis and myocarditis. Viral antigen was demonstrated by immunoperoxidase staining in the alveolar walls, around bronchi and blood vessels, and in focal areas of the adrenal cortex as early as 24-48 hours after infection. The virus disseminated probably hematogenously from the lungs and seemed to localize preferentially in the adrenals. In mice surviving the acute stage of infection a subcapsular cell reaction developed in the adrenal cortex. The extensive pneumonia and adrenal necrosis contributed to the high mortality rate of weanling mice infected with HSV-1. The route of viral inoculation and the age of the host animal seemed to influence the localization and outcome of the pathologic process.

Effects of chronic ACTH stimulation on the morphology of the rat adrenal cortex

Abstract: The effects of chronic ACTH treatment (Depot Synacthen, 100 micrograms/day) on the morphology of the rat adrenal were studied in animals treated for 1 to 18 days. The gross weight of the adrenal increased up to tenfold, but although mitotic figures were seen after 3 days in the glomerulosa region, most of this is attributable to a vast increase in blood content. After 3 days of treatment the sinusoids in the reticularis became extremely dilated, and red blood cells penetrated the endothelial wall to become tightly packed around the cortical cells. This led to the gross distortion of the organization of the cortical tissue and after 7 days the cells in the reticularis region were isolated from each other by the continual infiltration of red blood cells. These changes gradually progressed outward so that other regions of the cortex became similarly affected. Eventually the cord-like arrangement of the fasciculata was disrupted. After 18 days of treatment, most of the cortex was involved and only a very thin layer of cells lying beneath the adrenal capsule was seemingly unaffected. Another major effect of corticotrophin treatment was the gradual loss of cellular differentiation, particularly of glomerulosa cells. Although the glomerulosa appeared normal after 1 day of treatment, cells of the fasciculata abut directly on the connective tissue capsule following 3 days of ACTH administration. Eventually glomerulosa cells disappeared almost completely, although there was no sign of cellular necrosis. It is likely that glomerulosa cells are transformed into fasciculata-type cells under ACTH treatment. This interpretation is consistent with functional changes that occur at the same time, including the loss of aldosterone synthetic capacity.

Hypothalamic-Pituitary-Adrenal Axis

Abstract: Publisher Summary This chapter discusses tests used to diagnose disorders related to hypothalamic–pituitary–adrenal secretions. Dynamic testing procedures employed in the estimation of adrenal hypo- or hyperfunction are of three types—stimulation tests, suppression test, and repeated sampling for cortisol and/or adrenocorticotropic hormone (ACTH). Tests may stimulate the secretion of the adrenal cortex by exogenous administration of ACTH or stimulate endogenous secretion of ACTH following the administration of insulin or metyrapone. Suppression tests employ the administration of dexamethasone, although in unusual circumstances, cortisol may be employed to suppress ACTH secretion. Stimulation tests are utilized chiefly for the demonstration of normal adrenal reserve, thus indicating that there is sufficient adrenal tissue present for increased cortisol secretion to occur following ACTH administration. These tests are, thus, most useful in the demonstration of adrenal insufficiency but have also been found to have some application to the diagnosis of adrenal hyperfunction, particularly in the demonstration of partial enzyme deficiencies of congenital adrenal hyperplasia. A hyperactive response is characteristic of pituitary dependent Cushing's disease and lack of response is present in many but not all cortisol-secreting adrenal tumors.

Recent advances in 21-hydroxylase deficiency.

Abstract: A deficiency of 21-hydroxylase in the adrenal cortex results in insufficient cortisol production. The salt-wasting form of 21-hydroxylase deficiency is characterized by inadequate aldosterone production, as well. Because the hypothalamic-adrenal negative feedback system is broken, excess adrenal androgens are produced. This disordered corticosteroid production causes hormonal and clinical symptoms, including pseudohermaphroditism in genetic females and disordered puberty in both males and females. There is a spectrum of the time of onset and the severity of these symptoms. This disorder is inherited in an autosomal recessive manner. The 21-hydroxylase deficiency is genetically linked to the human leukocyte antigen (HLA) complex; in addition, nonclassical and classical 21-hydroxylase deficiency have each been shown to be in genetic linkage disequilibrium with specific HLA-B antigens. This genetic linkage, used in conjunction with baseline and stimulated serum hormonal levels, is useful in the diagnosis of this disorder. Prenatal diagnosis of homozygote, heterozygote, and unaffected fetuses is also available. Adequate treatment with glucocorticoid and mineralocorticoid replacement resolves symptoms and enables a normal life.

Adrenal and placental steroid secretion during pregnancy in the rat

Abstract: Studies were designed to determine the relative roles of the adrenal and ovary on androgen and progestin secretion in pregnant rats. Steroids were measured in serial plasma samples obtained from pregnant rats that had been ovariectomized, ovariectomized and adrenalectomized, or ovariectomized, adrenalectomized, and hypophysectomized and which had been treated with the steroid analogs dydrogesterone (9β,10α-pregna- 4,6-diene-3,20-dione) and diethylstilbestrol [(E)4,4′-(l,2-diethyl- l,2-ethenediyl)bisphenol] to maintain pregnancy. Plasma levels of progesterone and 20α-hydroxy-4-pregnen-3-one in pregnant rats were low on day 10, peaked on day 12 (21 ± 3 and 8 ± 1 ng/ml, respectively), and returned to low levels by day 16. Similar patterns of progestin levels were found in pregnant ovariectomized-adrenalectomized and ovariectomized-adrenalectomized- hypophysectomized rats maintained with steroid analogs. However, adrenalectomy caused lower levels of serum progesterone on days 10, 14, 16, and 18, demonstrating...

Studies on Cyclic Nucleotides in the Adrenal Gland. XI. Adrenergic Regulation of Adenylate Cyclase Activity in the Adrenal Cortex

Abstract: Adrenergic regulation of adenylate cyclase activities in the zona glomerulosa (the capsular fraction) and the zona fasciculata-reticularis (the decapsulated fraction) from rat adrenocortical glands has been investigated. Specific binding of [3H]dihydroalprenolol to the membrane from the capsular and the decapsulated fractions was saturable with dissociation constant (Kd) of 4.67 and 5.1 microM, respectively. The receptor density in the capsular and the decapsulated fractions was 230 and 235 fmol/mg protein, respectively. The potencies which isoproterenol, epinephrine, salbutamol, and norepinephrine competed with [3H]dihydroalprenolol binding sites indicted that adrenergic receptors of the capsular and the decapsulated membranes were of the beta 2-type. beta-Adrenergic stimulation of the adenylate cyclase system was observed only in the capsular fraction. This suggests that beta-adrenergic receptors of the capsular membrane are associated with their adenylate cyclase system, but those of the decapsulated membrane are not. Maximum stimulatory concentrations of ACTH and isoproterenol had no additive effect on the capsular adenylate cyclase, indicating that receptors for ACTH and beta-adrenergic agonists are coupled to a common pool of the cyclase.

Prolactin stimulates and potentiates adrenal steroid secretion in vitro.

Abstract: Prolactin, alone and in combination with ACTH, was tested for its ability to release steroids from rat adrenocortical slices superfused in vitro. The hormone possessed weak activity alone (minimal responsive dose = 1 U), but was able to potentiate the ACTH-stimulated corticoid release at much lower doses (significant response over ACTH alone at 0.01 U prolactin). This latter dosage was calculated to be within the physiologic range of prolactin in blood. Analysis of individual steroids in superfusate by RIA revealed that aldosterone release was most sensitive to prolactin, followed by corticosterone, androstenedione, and progesterone. We conclude that prolactin is an adrenocortical secretagogue of physiological relevance in the rat, and that it could play a role in enhancing the action of ACTH to acutely release steroids.

Cortisol Production by Cells Isolated from the Outer and Inner Zones of the Adrenal Cortex of the Guinea Pig

Abstract: Cortisol production by cells isolated from the outer (glomerulosa and fasciculata) and inner (reticularis) zones of the adrenal cortex of the guinea pig was evaluated in order to clarify the steroidogenic function of the zona reticularis. Basal cortisol production by the outer zone cells was 5-10 times greater than that by the inner zone cells. Cells from the outer zone increased cortisol production in response to ACTH (ED50, approximately 33 pg/ml), while cells from the inner zone failed to respond to ACTH. Likewise, cells from the outer zone increased cortisol production in response to (Bu)2cAMP, while cells from the inner zone failed to respond. When either pregnenolone or progesterone was added to the incubation mixture, an increase in cortisol production by cells of the inner zone was noted, although the increase was significantly less than that observed for cells from the outer zone. These results suggest that the zona reticularis of the guinea pig adrenal ordinarily produces little or no cortisol, although the enzyme machinery is present and capable of producing a limited amount of cortisol when supplied with the appropriate precursor.