Showing papers on "Adrenal cortex published in 1987"

Congenital adrenal hyperplasia

Abstract: Congenital adrenal hyperplasia is a group of autosomal recessive disorders resulting from the deficiency of one of the enzymes required for cortisol synthesis in the adrenal cortex. The most freque...

Adrenocortical Steroids and the Brain

Abstract: In summary, a wide variety of effects of adrenal steroids on the brain have been reported and have been recently and exhaustively reviewed. From the viewpoint of endocrine physiology, however, what is often forgotten is the extraordinary difference in signal level between the two unique products of the adrenal cortex, the mineralocorticoid and glucocorticoid hormones. Levels of cortisol or corticosterone are 2-3 orders of magnitude higher than those of aldosterone, a difference that is tempered by perhaps one order of magnitude by the much higher binding of glucocorticoids to plasma protein. The signal-detecting mechanisms for the lower-intensity signal, i.e. the mineralocorticoid receptor, must therefore have powerful specificity-conferring mechanisms to enable it to recognize, bind, and respond to aldosterone. In vitro studies from a number of laboratories have shown that Type I receptors, in both classic mineralocorticoid target tissues (kidney, parotid, gut) and nontarget tissues (pituitary, hippocampus), cannot distinguish between aldosterone and corticosterone. This finding highlights the problem of aldosterone-selectivity in the kidney (Na+ transport) or the brain (Na+ appetite). In vivo studies, in contrast, show that corticosterone is very poorly taken up and/or retained in kidney, colon, parotid, and pituitary (but not in hippocampus) in mature and 10-day-old (minimal transcortin) rats, whereas aldosterone is well taken up and/or retained by all tissues, evidence for tissue-specific aldosterone selectivity in vivo. Two nonexclusive (i.e. possibly additive) models for such aldosterone selectivity are proposed, one "prebinding" and the other "postbinding". Both models accommodate the experimental findings of the nonselectivity of cytosol preparations in vitro and the stringent specificity seen in in vivo receptor and effector studies. In any real sense, the action of adrenal steroids on the brain is still largely an area of unconnected phenomenology, despite the efforts of a number of talented individuals and groups over the past two decades. Without descriptions of phenomena, even of the most basic ablation and replacement type, we have no chance of making physiological statements. It is equally important, in the attempt to make a coherent physiology, to erect a scaffolding of hypothesis that can be tested against the existing experimental findings and that can serve to suggest further studies in a logical sequence. These hypotheses themselves, and the models used to reify them, may be validated, altered, or rejected by the studies over the next few years.(ABSTRACT TRUNCATED AT 400 WORDS)

The role of adrenal nerves in the regulation of adrenocortical functions.

Abstract: There is now convincing evidence for the distribution of several nerve plexuses in the outer zone of the adrenal cortex. At the ultrastructural level, the close proximity of nerve boutons to cortical cells establishes the anatomical substrate for a direct neural effect on adrenal cortical cell functions. Of those neurotransmitters and neuropeptides identified to date, catecholamine, VIP, and NPY appear to be most prevalent. Importantly, the amounts of morphologically identifiable catecholamine, VIP and NPY are differentially sensitive to alteration of several physiological conditions. Furthermore, the VIP plexus appears to be intrinsic to the adrenal while the catecholamine and NPY nerve fibers enter the adrenal along blood vessels. Together, these results suggest that these multiple nerve plexuses might exert control on several adrenocortical cellular processes in addition to the regulation of adrenal blood flow. Compensatory adrenal growth, a rapid proliferative response to unilateral adrenalectomy, was previously shown to be neurally mediated. The role of the catecholamine innervation in the mediation of this process has now been demonstrated. The elimination of the sympathetic nervous system by neonatal sympathectomy inhibited the proliferative response as measured by DNA synthesis. In vivo administration of beta-adrenergic receptor blockers did not inhibit the compensatory growth response. Furthermore, the beta-adrenergic agonist isoproterenol, inhibited the rate of DNA synthesis both in vivo and in vitro. The direct action of the beta-adrenergic agonist on the adrenocortical cell DNA synthesis rate suggests that the catecholaminergic nerves tonically inhibit cell proliferation associated with compensatory growth and that the release from the beta-adrenergic inhibition is necessary for compensatory growth. Whether inhibition of the beta-adrenergic innervation is the trigger for compensatory growth or whether it is permissive to the action of a still unidentified mitogenic substance, is not yet known. The direct role of VIP and catecholamines in the regulation of steroidogenesis has been investigated in vitro using the perifused capsule-glomerulosa preparation which is representative of a normal outer zone of the adrenal and is the site of the neural plexuses and identified receptors. Both VIP and isoproterenol stimulate steroidogenesis and specifically cause a greater increase in secretion of aldosterone than corticosterone. Although the concentrations of VIP and isoproterenol required to stimulate steroidogenesis are greater than reported circulating levels, release from resident nerves could provide high local concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Declining Adrenal Androgens: An Association with Bone Loss in Aging Women

Abstract: Bone loss in aging women is a major contributing factor to the onset of osteoporosis. To determine whether a decline in adrenal androgen output might be important in the loss of bone with age, we studied a highly selected group of 14 women, average age 70, and measured adrenal androgens in relationship to trabecular bone density. Dehydroepiandrosterone sulfate (DHEAS) levels were used as a marker of adrenal sex steroid output while quantitative, computerized tomography was used to determine trabecular bone density. Our results showed that both bone density (r = -0.69, P less than 0.01) and DHEAS levels (r = -0.68, P less than 0.01) declined with age, and that DHEAS was positively correlated with bone density (r = 0.66, P = 0.01). These data emphasize the association of declining adrenal sex steroid production with declining bone density during the process of aging.

Differential effects of the imidazole derivatives etomidate, ketoconazole and miconazole and of metyrapone on the secretion of cortisol and its precursors by human adrenocortical cells.

Abstract: The direct effects of etomidate, ketoconazole, miconazole and metyrapone were investigated on the secretion of cortisol and its precursors by dispersed cells from the adrenal cortex of a normal individual and four patients with Cushing's syndrome. The drugs interfered with adrenocorticotropic hormone-stimulated cortisol secretion in a dose-dependent way. Desoxycortisol concentrations in the medium were increased after the addition of metyrapone and low doses of etomidate but were suppressed with higher doses of etomidate. The production of 17-hydroxy-progesterone was stimulated by miconazole and metyrapone but was strongly suppressed by the high doses of etomidate. Ketoconazole caused a stimulation of progesterone release, whereas the release of 17-hydroxyprogesterone was suppressed. Finally, the concentration of progesterone was strongly enhanced with high doses of miconazole, whereas etomidate suppressed progesterone production. It is concluded that etomidate at a low concentration (IC50, 10(-8) M) inhibits 11 beta-hydroxylase, whereas, at higher concentrations (10(-7)-10(-6) M), the side-chain cleavage enzyme system is also inhibited; metyrapone is a weaker (IC50, 10(-7) M) but pure 11 beta-hydroxylase inhibitor; miconazole inhibits adrenal 21-hydroxylase at 10(-6) M; and ketoconazole inhibits 17-hydroxylase. Etomidate, ketoconazole, miconazole and metyrapone inhibit cortisol biosynthesis in the human adrenal gland in different manners, which appear to involve the four cytochrome P-450-dependent monooxygenase reactions. Interestingly, these drugs affect corticosteroidogenesis by normal, hyperplastic and adenomatous adrenal cells in a similar manner.

Diminished Diurnal Secretion of Adrenocorticotropin (ACTH), But Not Corticosterone, in Old Male Rats: Possible Relation to Increased Adrenal Sensitivity to ACTH in Vivo*

Abstract: The diurnal secretion of ACTH and corticosterone was examined in chronically cannulated young (3-4 months old), middle-aged (10-12 months old), and old (22-24 months old) Fischer 344 male rats. Plasma corticosterone in young rats increased from baseline concentrations of 78 +/- 5 to a maximum of 171 +/- 24 ng/ml at 1730 h and declined to basal levels by 1930 h. Middle-aged and old rats demonstrated a similar magnitude and time course of corticosterone release. However, comparison of the relative concentrations of ACTH released during the diurnal surge revealed that old rats secreted 35% less ACTH than young or middle-aged animals (P less than 0.05). Age-related changes in the sensitivity of the adrenal gland to a submaximal dose of ACTH were tested in dexamethasone-pretreated animals at 1100 and 1700 h in a separate experiment. Plasma corticosterone levels were significantly greater after ACTH administration (1 mIU/kg ACTHAR, iv) at 1700 h in both young and old rats compared to 1100 h values (P less than 0.05), and levels 20 min post-ACTH injection at 1700 h were significantly greater in old than young or middle-aged rats at the same time (P less than 0.05). These results demonstrate that 1) there are no age-related changes in the diurnal secretion of corticosterone in Fischer 344 male rats; 2) there is a decline in the peak level of ACTH during the diurnal surge of old compared to young animals; and 3) adrenal sensitivity to ACTH at 1700 h is greater in old compared to young or middle-aged rats. We hypothesize that the greater increase in adrenal sensitivity to ACTH is responsible for the maintenance of the corticosterone rhythm in the presence of diminished ACTH concentrations in older rats.

An ACTH receptor on human mononuclear leukocytes. Relation to adrenal ACTH-receptor activity.

Abstract: THE inaccessibility of many tissues makes routine investigation for receptor defects impossible. ACTH insensitivity syndrome, first described by Shepard et al.1 in 1959 and now reported in more tha...

On the presence of chromaffin cells in the adrenal cortex: their possible role in adrenocortical function.

Abstract: Using light and electron microscopy, we have observed the presence of rays containing medullary tissue extending across the cortex of rat adrenal glands. Within these rays chromaffin cells, as well as collagen and nerve fibers, were present. It is suggested that these endocrine cells may have a paracrine function within the cortex, possibly via their secretory product.

Bone mineral density in Addison's disease: evidence for an effect of adrenal androgens on bone mass.

Abstract: It is unknown whether replacement doses of cortisone acetate and the absence of the small amounts of androgens secreted by the adrenal cortex may cause osteoporosis. This was studied in 35 patients (12 men and 23 women) suffering from primary adrenocortical failure and taking cortisone acetate 25-37.5 mg and fludrocortisone 50-100 micrograms daily. Bone mineral density was measured by single photon absorptiometry at the midshaft of the radius, representing cortical bone, and at the distal part of the radius, a site with a significant trabecular component. The bone mineral density was normal in premenopausal female patients as well as in male patients, showing that replacement doses of cortisone acetate do not affect bone mass. By contrast, in postmenopausal patients there was a dramatic bone loss in addition to the physiological postmenopausal decrease in bone mass. This loss, combined with the low plasma concentrations of androstenedione, dehydroepiandrosterone, and testosterone (and low concentrations of oestrone of adrenal origin), indicates that adrenal androgens may be essential for the maintenance of bone mass in postmenopausal women with Addison's disease. In addition, these data indicate that the small amounts of androgens secreted by the adrenal cortex have a role in the maintenance of bone mass in normal postmenopausal women.

Electrical properties of isolated rat adrenal glomerulosa and fasciculata cells

Abstract: Passive and active electrical properties of isolated rat adrenal glomerulosa and fasciculata cells were studied by intracellular voltage-recording and constant current stimulation. The average resting membrane potential was -78.9 +/- 4.2 mV for glomerulosa cells and -77.8 +/- 5.0 mV for fasciculata cells. The response of the membrane potential to changes in external K+ concentration was stable and reversible for changes up to 28 mM and was independent of external Cl-. The relationship between membrane potential and the log of external K+ concentration was linear between 4 and 28 mM, and the membrane potential could be predicted by a simplified form of the constant field equation with a [K]i of 138.5 mM and a PNa/PK of 0.015 for glomerulosa cells and a [K]i of 112.4 mM and a PNa/PK of 0.011 for fasciculata cells. Under current clamp conditions, both cells demonstrated a nonlinear relationship between membrane voltage and applied current for depolarizing current steps. Depolarizing current pulses elicited a regenerative response and were followed by a rectifying steady state potential. The maximum rate of rise and the peak amplitude of the regenerative response were increased by prior hyperpolarization below the resting membrane potential and decreased by depolarization. The regenerative response was unaffected by the removal of Na+. Elevated Ca2+ concentrations increased the rate of rise, peak amplitude, and rate of fall, but decreased the duration of the regenerative response. The regenerative response was maintained upon replacement of Ca2+ with Sr2+ or Ba2+, but was inhibited by Mn2+ or Co2+. Regenerative responses elicited in both glomerulosa and fasciculata cells exhibited similar characteristics. The results suggest the ionic mechanism underlying the regenerative response to be a voltage-dependent Ca2+ conductance. Both adrenal glomerulosa and fasciculata cells demonstrate electrical properties in common with other excitable cells. They are good K+ sensors with regard to their membrane potential, approaching the maximum sensitivity expected for a membrane exclusively permeable to K+. In addition, the Ca2+ regenerative response, which has been identified in both adrenal glomerulosa and fasciculata cells, may be involved in secretagogue stimulation of steroidogenesis.

α-Inhibin Gene Expression Occurs in the Ovine Adrenal Cortex, and is Regulated by Adrenocorticotropin

Abstract: Inhibin is a glycoprotein hormone composed of two nonidentical subunits. It is produced by the ovary and testis and plays a vital role in gonadal function by inhibiting the secretion of FSH. More recently, additional activities associated with inhibin peptides have been identified. Inhibin heterodimers (α-β) are reported to act directly on ovarian granulosa cells and inhibit estrogen production induced by FSH. Furthermore, homodimers of β-inhibin subunits stimulate the secretion of FSH, an activity that is directly opposite to that of inhibin. Each of these inhibinrelated activities are concerned with the hypothalamic-pituitary-gonadal axis. We have investigated further the complexity of inhibin activity by determining whether inhibin genes are expressed in nongonadal tissue. RNA hybridization experiments demonstrate that the α-inhibin gene is expressed in the sheep adrenal cortex and hybridization histochemistry shows that this gene is expressed in each of the functional zones within the cortex. Dot blot...

Control of circadian and episodic variations of adrenal androgens secretion in man

Abstract: The 24-h profiles of plasma cortisol (F), 11-β-hydroxyandrostenedione (11OHAD), androstenedione (AD), dehydroisoandrosterone (DHEA) and testosterone (T) were obtained simultaneously in 11 normal males sampled at 15-min intervals. The data were submitted to a detailed quantitative analysis including the estimation of the circadian rhythm and of the episodic variations as well as the evaluation of the concomitance of episodic pulses of different hormones. A bimodal circadian rhythm was detected in the various individual profiles. The major acrophase occurred in the morning earlier for T (around 04:00 h) than for the hormones of totally or partially adrenal origin (around 07:00 h); the secondary acrophase (around 17:00 h) and the main midnight nadir were common to all hormones. The amplitude of the rhythm was highest for purely adrenal hormones (F and 11OHAD), averaging 79 and 75%, respectively, lower for hormones of mixed origin (DHEA and AD), averaging 44 and 42%, respectively, and minimal for T (22%). The possible relationship between the circadian and pulsatile variations of the various steroids was estimated in each individual by calculating Pearson’s standard coefficient of variation on all pairs of hormonal profiles. A very tight relationship (r > 0.75; p 0.30; p 0.30; p < 0.01). The pulsatility of the corticotrophic axis was readily transmitted to the secretory pattern of 11OHAD, DHEA and AD. Ninety-six percent of the F pulses were reflected in at least one other hormonal profile. Finally, we showed that concomitant pulses common to the five adrenal and gonadal patterns were more frequent than would be expected on the basis of chance. These results: (1) demonstrate a total parallelism between the long-lasting secretory events and the episodic bursts of the 4 adrenal hormones showing that the reticular and fascicular zones of the adrenal respond to pituitary control as an homogeneous structure; (2) demonstrate the existence of a partial synchronization of adrenal and testicular pulsatile variations; (3) suggest that, throughout the afternoon, a common mechanism may influence the slow variations of adrenal hormones and of testicular testosterone.

Corticotropin-releasing factor in the dog adrenal medulla is secreted in response to hemorrhage.

Abstract: To characterize the nature of CRF-like immunoreactivity (CRF-LI) in the dog adrenal, adrenal medullary, adrenal cortical, or hypothalamic tissue was extracted and subjected to RIA after partial purification on C-18 cartridges or Sephadex G-50. Using N- and C-terminal-directed antisera against rat/human (r/h) CRF, significant levels of CRF-LI were found in the adrenal medulla and hypothalamus, but not in the adrenal cortex. Immunocytochemical analysis revealed that CRF-immunoreactive cells were located in the adrenal medulla, many of them concentrated in the vicinity of blood vessels and at the border between adrenal medulla and cortex. However, the cortex was devoid of any CRF-positive cells. On reverse phase HPLC, CRF-LI in the adrenal medulla coeluted with synthetic r/hCRF. In a bioassay system, using dispersed rat anterior pituitary cells, purified adrenal CRF caused a dose-dependent increase in ACTH secretion parallel to the r/hCRF standard, indicating that dog adrenal medulla contains authentic r/hCR...

Electrophysiological responses to angiotensin II of isolated rat adrenal glomerulosa cells.

Abstract: The membrane response of isolated rat glomerulosa cells to the application of angiotensin II (A II) has been studied using intracellular voltage measurements. The membrane response is biphasic. The first, brief phase involves an increase in membrane conductance and a hyperpolarization from the resting membrane potential. The second, long-lasting phase is characterized by a large decrease in membrane conductance and a depolarization from the resting membrane potential. The reversal potential for the second phase is -94 +/- 1.2 mV, and a linear relationship between reversal potential and external K+ indicates that the A II-mediated response is predominantly inhibition of K+ permeability. The A II response can be elicited when external Ca2+ is replaced by Sr2+ or Ba2+, but the response is inhibited when Mn2+ is added to the bath or when stimulated in a Ca2+-free solution. A II appears to inhibit at least two conductances, when the cell is stimulated by long current steps. External application of A II inhibited the Ca2+ regenerative response found in glomerulosa cells in a dose-dependent manner. The rate of rise of the regenerative response was greatly attenuated by A II; half-maximal inhibition was produced by about 10(-9) M A II. In addition, rectification, evident at voltages more positive than -60 mV during current stimulation, was also inhibited. In conclusion, A II causes rat glomerulosa cells to depolarize due to the inhibition of resting K+ permeability. Action potential activity is not observed during A II-mediated membrane depolarization; rather, both Ca2+ and K+ conductances appear to be inhibited during A II application.

Basic fibroblast growth factor: production and growth stimulation in cultured adrenal cortex cells.

Abstract: Cultured bovine adrenal cortex cells express the basic fibroblast growth factor (bFGF) gene and contain, but under normal conditions apparently do not release, bFGF. However, once released, bFGF can stimulate proliferation of the cells, indicating that it could act as a self-stimulating growth factor for adrenal cortex cells. It is conceivable that the intracellular bFGF is released upon injury of the adrenal cortex and that it may be involved in the subsequent tissue repair mechanisms by stimulating the proliferation of adrenal cortical and vascular endothelial cells. (Endocrinology 120: 796–800, 1987)

Functional and scintigraphic evaluation of the silent adrenal mass

Abstract: Seven patients with unilateral and one patient with bilateral and asymmetric (R greater than L) incidentally discovered adrenal mass abnormalities depicted by computed tomography (CT) were studied by 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) scintigraphy. There was marked lateralization of NP-59 uptake to the side of the mass lesion in the seven patients with unilateral masses and prominent asymmetric, (R greater than L) bilateral uptake in the patient with bilateral masses despite the fact that there were no obvious abnormalities of adrenocortical or adrenomedullary function as determined from peripheral blood and 24-hr urinary hormone measurements. Simultaneous bilateral adrenal vein catheterization (AVC) was employed to measure the levels of hormone effluent from the adrenal cortex and medulla and in all instances the cortisol concentrations were greatest from the side of the mass lesion in those patients with unilateral masses and from the larger of the two adrenals in the patient with bilateral adrenal masses. Thus, there was congruence between the anatomic (CT) and functional (NP-59 scintigraphy and AVC) investigations that depicted asymmetry of the adrenal glands which were not associated with abnormalities of overall adrenal function or hypothalamic-pituitary-adrenal axis integrity.

Molecular markers of neuroendocrine development and evidence of environmental regulation

Abstract: We constructed a human pheochromocytoma cDNA library and used differential hybridization to human pheochromocytoma and human neuroblastoma cDNA probes to isolate genes that are highly expressed in the adrenal medullary neuroendocrine tumor, pheochromocytoma, but not in the more immature embryonal tumor of adrenal medulla, neuroblastoma. Two cDNA clones, pG8 and pG2, were more highly expressed in normal and neoplastic chromaffin tissue than they are in neuroblastoma. Furthermore, they are expressed in a remarkably limited number of other human tumors or normal tissues. pG8 is highly expressed in medullary thyroid carcinoma, another tumor of neural crest origin, which can occur in association with pheochromocytoma in the multiple endocrine neoplasia type II syndrome. pG2 is highly expressed in the adrenal cortex, an endocrine gland thought to be embryologically unrelated to the neural crest-derived adrenal medulla. The expression of both pG8 and pG2 can be induced in human neuroblastoma cells with dexamethasone, suggesting a mechanism by which glucocorticoids may influence development of a neuroendocrine phenotype.

The effect of splanchnic nerve section on the sensitivity of the adrenal cortex to adrenocorticotrophin in the calf.

Abstract: 1. Adrenal cortical responses to adrenocorticotrophin (ACTH) in conscious 2-6-week-old calves, in which both splanchnic nerves had been cut at least 7 days previously, were compared with those of normal calves of the same age in order to discover whether splanchnic nerve section affects the sensitivity of the adrenal cortex to the trophin. 2. In one series of experiments an increase in the release of endogenous ACTH was elicited by an i.v. infusion of noradrenaline (333 ng min-1 kg-1 for 10 min) and in another the concentration of ACTH in the plasma was artificially increased by infusing synthetic ACTH1-24 intravenously at either 5 or 10 ng min-1 kg-1 for 10 min. 3. In all groups mean plasma ACTH was linearly related to mean plasma cortisol and the sensitivity of the adrenal steroidogenic response to ACTH was found to be substantially reduced 7 or more days after section of both splanchnic nerves.

Sex differences in adrenocortical structure and function. XXIV. Comparative morphometric studies on adrenal cortex of intact mature male and female rats of different strains.

Abstract: The zonation and cellular composition of the adrenal cortex of intact mature male and female rats of different strains (Chbb Thomm, CFY) and three strains of Wistar rats (W1, W2 and W3) at the age of 84-90 days were compared using morphometry. Both absolute and relative adrenal gland weights were higher in female than male rats. Rats of W3 and Chbb Thomm strains had the largest adrenals. These differences depended upon the higher volume of the zona fasciculata (ZF) and zona reticularis (ZR) in the W3 and Chbb Thomm strains than in the remaining animals. Females had larger adrenocortical zones than corresponding males. The average volume of the ZF cell ranged in males from 1589 micron 3 (W1 strain) to 2111 micron 3 (Chbb Thomm) and in females from 2249 micron 3 (W1 strain) to 2894 micron 3 (W3 strain). The average nuclear volume of the ZF cells was higher in female rats whereas there were no strain- and sex-differences in the size of zona glomerulosa (ZG) and ZR cells. The total number of parenchymal cells per pair of adrenals varied markedly among the studied strains, with the highest number in W3 and Chbb Thomm females. W3, Chbb Thomm and CFY females had larger number of parenchymal cells than males; the reverse was true for W1 strain whereas no differences were found among W2 male and female rats.

Physicochemical Characterization of Photoaffinity-Labeled Angiotensin II Receptors

Abstract: Specific receptor sites for angiotensin II (All) were analyzed in the adrenal cortex and other target tissues including liver, anterior pituitary gland, and smooth muscle, after covalent labeling with the radioactive photoaffinity analog 125l-[Sar1,(4-N3)Phe8]-All. The photoreactive All derivative retained high affinity for adrenal receptors and full steroidogenic activity in adrenal glomerulosa cells. In bovine adrenal cortex, covalent labeling of All receptors by the photoreactive analog was specifically inhibited by [Sar1]All with an IC50 of about 5 nm. The Mr of the covalent All-receptor complex during polyacrylamide gel electrophoresis of the labeled protein under reducing conditions was 58,000. Under nonreducing conditions, a minor band with Mr of 105,000 was also observed. Two labeled species were also found during gel permeation chromatography of the detergent-solubilized complex, with Mrs of 64,000 and 86,000. The pl of the solubilized photolabeled complex was absorbed to wheat germ lectin Sephar...

Transient Ca2+-channel current characterized by a low-threshold voltage in zona glomerulosa cells of rat adrenal cortex

Abstract: Voltage-gated Ca2+-current was identified in single isolated cells of the zona glomerulosa of adrenal cortex and its properties were studied by the “tight-seal” whole cell recording technique. The Ca2+-channel current was dissected from the net current by dialyzing the cells with CsCl. The identified Ca2+-current was found to be activated by a relatively small depolarization only when the cells were held at a large negative holding potential, but it was inactivated within 10–30 ms. The time course of activation and inactivation was voltage-dependent and became faster when the amplitude of depolarization was increased. The transmembrane potential of the glomerulosa cells was highly sensitive to [K+]e, the slope of the potential change per tenfold change in [K+]e being 48 mV. An increase in [K+]e from 4.7 to 10 mM induce a membrane depolarization by 15 mV, which was sufficient to cause the membrane to reach the threshold potential (−60 mV) for activation of the Ca2+-current at physiological concentration of [Ca2+]e (2.5 mM −CaCl2). The observed properties of the Ca2+-current and K+-dependence of the membrane potential may give reasonable explanation for the mechanism of Ca2+-uptake and consequent aldosterone secretion induced by a small increase in [K+]e, which is known to be one of the major stimulations for aldosterone secretion.

Glucocorticoids, adrenal medullary opioids, and the retention of a behavioral response after stress.

Abstract: In the Porsolt model swimming test, naive rats become progressively more immobile over a 15-min initial test (0-5 min, -30% immobile; 5-10 min, -50%, 10-15 min, -70%). Twenty-four hours later, rats have retained the response, being immobile for about 70% of a 5-min retest period. We previously reported that in this test adrenalectomized rats are indistinguishable from intact rats over the 15-min test period, but are immobile for only approximately 30% of a 5-min retest period 24 h later. The finding that this behavioral effect of adrenalectomy can be reversed by glucocorticoids or K-selective opioids led us to hypothesize that retention of the immobile behavior can be effected by glucocorticoids from the adrenal cortex or K-selective opioids from the adrenal medulla. To test this hypothesis, we have given intact rats the antiglucocorticoid RU38486 and the anticholinergics atropine and mecamylamine to block adrenal medullary discharge, either alone or simultaneously. Administered alone, neither class of an...