Evidence for increased endogenous dopaminergic inhibition of aldosterone secretion in prolactinoma

Aldosterone responsiveness to consecutive i.v. injections of metoclopramide 1 mg, 2.5 mg and 10 mg was studied in 8 patients with prolactinoma and normally preserved adrenal function and in 14 healthy volunteers. In the patients, aldosterone response to metoclopramide 1 mg was blunted. After metoclopramide 10 mg, aldosterone rose to the same levels in patients and volunteers. In the patients, however, percentage rise of aldosterone was enhanced, since the appropriate base line concentration of aldosterone was decreased. Thus, there is evidence for increased endogenous dopaminergic inhibition of aldosterone secretion in prolactinoma.     

Metoclopramide fails to stimulate aldosterone secretion and inhibits serotonin-mediated aldosterone secretion in the rat

The acute and chronic effects of metoclopramide on aldosterone secretion in the rat model were examined. Metoclopramide 50 micrograms iv in dexamethasone-treated rats did not increase plasma aldosterone concentration. Chronic infusion of metoclopramide (72 micrograms/hr) over 5 days also did not show any increase in the plasma or urinary aldosterone concentration when compared with control rats. Metoclopramide in vitro showed no effect on aldosterone secretion from rat adrenal capsular cells but it inhibited serotonin-mediated aldosterone secretion from the same cells significantly.     

Changes in aldosterone and cortisol secretion and serum thyroxine levels in patients with active urolithiasis

The changes in calcemia and calciuria levels following low calcium diet have been studied in 35 patients with active urolithiasis and in 20 healthy subjects. Blood serum concentrations of thyroxine, cortisol and aldosterone in basal conditions as well as cortisol and aldosterone following stimulation with synacten were determined in addition. The levels of calcemia and calciuria (2.56 +/- 0.015 mmol/l and 4.70 +/- 0.41 mmol/10 mmoles of creatinine, respectively) were found to be significantly higher in patients with active urolithiasis than in healthy subjects. In addition, in patients with urolithiasis the basal blood serum concentrations of thyroxine and aldosterone were significantly higher than in healthy subjects, while the reactivity of cortisol and aldosterone secretion to synacten stimulation was normal. The results obtained suggest the participation of the described hormonal aberrations in the pathogenesis of active urolithiasis.     

Plasma renin activity, aldosterone and cortisol secretions after acute hemorrhage and supine to vertical postural change in dogs

Acute hemorrhage and horizontal to vertical postural change are accompanied by decrease in blood volume of cardiovascular central reflexogenic areas (CRA) and by central hypoxia, followed by pressor responses. In these both circumstances important reflexogenic and humoral pressor reactions occured, as cathecolamine, renin and aldosterone hypersecretions. Aldosterone hypersecretion is considered as produced by angiotensin II, by a complex renin-angiotensin(RA)-aldosterone system. The main purpose of this work was to clarify the presence of this RA-aldosterone system after acute hemorrhage and in head-up postural change. In this aim we studied on dogs renin, aldosterone and cortisol responses. We analysed in these two circumstances the correlation of plasma renin activity(PRA) and aldosterone plasma concentration(p.c.) in intact and bilaterally nephrectomised(BN) dogs. We also studied correlations between aldosterone and cortisol p.c., having in view that both are stimulated by ACTH, searching in this way another modality for aldosterone secretion.     

Evidence for a cold-induced aldosterone stimulation in the rat

This study was undertaken to determine the secretion of aldosterone by male Long-Evans rats acclimated for six weeks to moderate cold (15 C), in comparison with rats maintained at thermo-neutral temperature (28 C). The following determinations were made: corticosteroids in plasma and adrenals, PRA, and hydromineral balance. Cold acclimation highly increased the plasma and adrenal levels of aldosterone and corticosterone. The cold stimulation of aldosterone was induced neither by the renin-angiotensin system, nor by alterations of hydromineral balance: PRA, plasma sodium and potassium concentrations, blood hematocrit, and hydromineral balance at 15 C and 28 C did not differ. Moreover this stimulation was induced neither by ACTH, nor by any other hypophyseal factors, since plasma aldosterone levels remained high in hypophysectomized rats. This study provides evidence of an aldosterone stimulation which appeared during moderate cold acclimation; the origin of this stimulation must be investigated.     

Evidence for a paracrine role of adrenomedullin in the physiological resetting of aldosterone secretion by rat adrenal zona glomerulosa

Adrenomedullin (ADM) has been recently found to directly inhibit agonist-stimulated aldosterone secretion by dispersed zona glomerulosa (ZG) cells and to stimulate basal catecholamine release by adrenomedullary fragments. In light of the fact that catecholamines enhance aldosterone secretion acting in a paracrine manner, we have investigated whether these two effects of ADM may interact when the integrity of the adrenal gland is preserved. ADM increased basal aldosterone output by adrenal slices containing a core of adrenal medulla, and the effect was blocked by the beta-adrenoceptor antagonist l-alprenolol. In contrast, ADM evoked a moderate inhibition of K(+)-stimulated aldosterone production, and the blockade was complete in the presence of l-alprenolol. The in vivo bolus injection of ADM did not affect plasma aldosterone concentration (PAC) in rats under basal conditions. Conversely, when rat ZG secretory function was enhanced (by sodium restriction or infusion with angiotensin-II [ANG-II]) or depressed (by sodium loading or infusion with the angiotensin-converting enzyme inhibitor captopril), ADM evoked a sizeable decrease or increase in PAC, respectively. The prolonged infusion with the ADM receptor antagonist ADM(22-52) caused a further enhancement of PAC in sodium-restricted or ANG-II-treated rats, and a further moderate decrease of it in sodium-loaded or captopril-administered animals. RIA showed that ADM plasma concentration did not exceed a concentration of 10(-11) M in any group of animals. Under basal conditions, ADM adrenal content was 1.2-2.0 pmol/g, which may give rise to local concentrations higher than 10(-8) M (i.e. well above the minimal effective ones in vitro). ADM adrenal concentration was markedly increased (from two-fold to three-fold) by both ZG stimulatory and suppressive treatments. Collectively, our findings suggest that in vivo 1) ADM, in addition to directly inhibit aldosterone secretion, may enhance it indirectly by eliciting catecholamine release, the two actions annulling each other under basal conditions; 2) under conditions leading to enhanced aldosterone secretion, the direct inhibitory effect of ADM prevails over the indirect stimulatory one, and the reverse occurs when aldosterone secretion is decreased; and 3) the modulatory action of ADM on the aldosterone secretion has a physiological relevance, endogenous ADM being locally synthesized in adrenals.     

Absent aldosterone response to metoclopramide in patients with high spinal cord transection: evidence that metoclopramide stimulates aldosterone secretion through central pathways

This study evaluates dopaminergic regulation of aldosterone secretion in 6 patients with high spinal cord transections. Administration of the dopamine antagonist metoclopramide resulted in a marked rise in plasma aldosterone and 18-hydroxycorticosterone levels in 12 normal individuals, but no change in plasma levels of these zona glomerulosa corticosteroid products in spinal cord patients. Spinal cord transected patients also did not have the rise in plasma renin activity that was observed in normals following metoclopramide administration. Basal levels of aldosterone, 18 hydroxycorticosterone, corticosterone and renin activity as well as the aldosterone responses to graded dose infusion of adrenocorticotropin were similar in the spinal cord patients and the normals. These data suggest that dopaminergic regulation of adrenal zona glomerulosa corticosteroid and renal renin secretion is absent in patients with high spinal cord transections, suggesting that intact neural pathways from the central nervous system are necessary for metoclopramide stimulation of aldosterone and renin secretion in men. Since basal plasma aldosterone levels were normal in spinal cord transected patients, it appears that the absence of dopaminergic control does not result in elevated secretion.     

The cortisol response to awakening in relation to different challenge tests and a 12-hour cortisol rhythm.

Recent studies have shown that cortisol levels rapidly increase within the first 30 minutes after awakening. This response is rather robust over weeks or months and is altered by chronic stress and burnout. The present study investigated to what extent the cortisol response to awakening relates to responses following hCRH, ACTH(1-24), or psychosocial stress challenges in 22 healthy subjects. Furthermore, a 12-hour circadian cortisol profile was obtained to compare the morning response with cortisol levels obtained throughout the day. Results show that the morning cortisol response was of similar magnitude to that following injection of 1 microg/kg h-CRH or exposure to a brief psychosocial stressor (TSST). All of these were significantly smaller compared to maximal stimulation of the adrenal cortex by ACTH(1-24). Correlation analyses revealed that the morning cortisol response was closely related only to the cortisol response following 0.25 mg ACTH(1-24) (r=0.63, p=0.002). We conclude that the morning cortisol response to awakening can provide important information on the (re)activity of the HPA axis in addition to more 'traditional' methods like hCRH or Synacthen challenge tests. The sensitivity/capacity of the adrenal cortex appears to play a crucial role for the magnitude of cortisol responses observed after awakening.     

Co-secretion of aldosterone and cortisol by an adrenocortical carcinoma

We report a rare case of adrenocortical carcinoma. A 26-year-old woman presented with hypokalemia and hypertension due to hyperaldosteronism. She had no signs of Cushing's syndrome. Endocrinological data showed excess of aldosterone production and nonsupressible cortisol production on 2 mg of dexamethasone. Magnetic resonance imaging showed left adrenal tumor. Transabdominal left adrenalectomy was performed and histopathological diagnosis was adrenocortical carcinoma. Her blood pressure and hypokalemia returned to normal after adrenalectomy. There is no recurrence after 36 months. We want to emphasis the importance of adrenal tests before the operation even if there are no signs of excess cortisol production.     

Testosterone and cortisol jointly regulate dominance: Evidence for a dual-hormone hypothesis

Traditional theories propose that testosterone should increase dominance and other status-seeking behaviors, but empirical support has been inconsistent. The present research tested the hypothesis that testosterone's effect on dominance depends on cortisol, a glucocorticoid hormone implicated in psychological stress and social avoidance. In the domains of leadership (Study 1, mixed-sex sample) and competition (Study 2, male-only sample), testosterone was positively related to dominance, but only in individuals with low cortisol. In individuals with high cortisol, the relation between testosterone and dominance was blocked (Study 1) or reversed (Study 2). Study 2 further showed that these hormonal effects on dominance were especially likely to occur after social threat (social defeat). The present studies provide the first empirical support for the claim that the neuroendocrine reproductive (HPG) and stress (HPA) axes interact to regulate dominance. Because dominance is related to gaining and maintaining high status positions in social hierarchies, the findings suggest that only when cortisol is low should higher testosterone encourage higher status. When cortisol is high, higher testosterone may actually decrease dominance and in turn motivate lower status.     

Testosterone and cortisol jointly regulate dominance: Evidence for a dual-hormone hypothesis

Traditional theories propose that testosterone should increase dominance and other status-seeking behaviors, but empirical support has been inconsistent. The present research tested the hypothesis that testosterone's effect on dominance depends on cortisol, a glucocorticoid hormone implicated in psychological stress and social avoidance. In the domains of leadership (Study 1, mixed-sex sample) and competition (Study 2, male-only sample), testosterone was positively related to dominance, but only in individuals with low cortisol. In individuals with high cortisol, the relation between testosterone and dominance was blocked (Study 1) or reversed (Study 2). Study 2 further showed that these hormonal effects on dominance were especially likely to occur after social threat (social defeat). The present studies provide the first empirical support for the claim that the neuroendocrine reproductive (HPG) and stress (HPA) axes interact to regulate dominance. Because dominance is related to gaining and maintaining high status positions in social hierarchies, the findings suggest that only when cortisol is low should higher testosterone encourage higher status. When cortisol is high, higher testosterone may actually decrease dominance and in turn motivate lower status.     

Exploration of the awakening cortisol response in relation to diurnal cortisol secretory activity

Adrenocortical activity can be assessed by measurement of free cortisol in saliva. Cortisol status has important health implications in both physical and psychological terms. Assessment of cortisol status is complicated by the marked diurnal cortisol cycle. This cycle is characterised by an increase in secretory activity following awakening to achieve the morning acrophase. Thereafter it falls with a declining trend over the remainder of the day. For between subject studies the timing of sampling in relation to this cycle is an important consideration. We report a comprehensive study of the diurnal free cortisol cycle designed to analyse its components and to investigate their reliability and inter-relatedness. We instructed 42 healthy volunteers to collect saliva samples at home on two consecutive days. On each day the first sample was collected immediately upon awakening, followed by a further three samples at 15-minute intervals which collectively comprised the "awakening samples". A further four sample's were collected through the day at 3-hour intervals, all synchronized to awakening time. The cortisol response to awakening was calculated in two ways. Overall cortisol production in the first 45 minutes after awakening was calculated as area under the cortisol curve with reference to zero (AUC). The dynamic of the cortisol response to awakening was calculated as area under the cortisol response curve (AURC) with reference to the first awakening sample. In addition the underlying cortisol secretory activity was assessed based upon the diurnal three-hourly samples. All three parameters of adrenocortical activity showed reasonable stability across the two sampling days indicating all were reliable indexes of trait characteristic. AUC was representative of underlying diurnal activity but AURC was not. Measurement at any time point, 3, 6, 9 or 12 hours post-awakening was representative of the underlying 12-hour diurnal activity.     

Regulation of aldosterone secretion in primary aldosteronism.

Plasma aldosterone, plasma renin activity and plasma cortisol were determined in patients with primary aldosteronism in response to posture and at short-time intervals overnight while the patient were supine. In the 5 patients with an aldosterone-producing adenoma postural changes in plasma aldosterone were paralleled by those in cortisol while plasma renin activity was generally undetectable indicating an ACTH-dependent secretion of aldosterone. This concept was supported by the observation that in 3 of these patients who were tested overnight 1. episodic secretion of plasma aldosterone was paralleled by those of cortisol and 2. episodic secretion of plasma aldosterone could be blunted by dexamethasone. In the patient with idiopathic adrenal hyperplasia concomittant changes in plasma aldosterone and plasma renin activity occurred. The assumption that in this patient the fluctuations in plasma aldosterone were mediated through changes in renal renin secretion was supported by the finding that episodic secretion of plasma aldosterone persisted under suppression of ACTH-secretion by dexamethasone. Our results indicate, that the described procedures may all serve as diagnostic criteria to differentiate between aldosterone-producing adenoma and idiopathic adrenal hyperplasia.