Because 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to play roles in both proliferation and differentiation of novel target cells, the potential expression of 1,25(OH)2D3 receptor (VDR) activity was investigated in cultured bovine aortic endothelial cells (BAEC). Receptor binding assays performed on nuclear extracts of BAEC revealed a single class of specific, high-affinity VDR that displayed a 4.5-fold increase in maximal ligand binding (Nm.x) in rapidly proliferating BAEC compared with confluent, density-arrested cells. When confluent BAEC were incubated with activators of protein kinase C (PKC), N., increased 2.5-fold within 6-24 h and this upregulation was prevented by sphingosine, an inhibitor of PKC, as well as by actinomycin D or cycloheximide. Immunohistochemical visualization using a specific MAb disclosed nuclear localized VDR in venular and capillary endothelial cells of human skin biopsies, documenting the expression of VDR, in vivo, and validating the BAEC model. Finally, additional experiments indicated that BAEC formed the 1,25(OH)2D3 hormonal metabolite from 25(OH)D3 substrate, in vitro, and growth curves of BAEC maintained in the presence of 10-8 M 1,25(OH)2D3 showed a 36% decrease in saturation density. These data provide evidence for the presence of a vitamin D microendocrine system in endothelial cells, consisting of the VDR and a la-hydroxylase enzyme capable of producing 1,25(OH)2D3. That both components of this system are coordinately regulated, and that BAEC respond to the 1,25(OH)2D3 hormone by modulating growth kinetics, suggests the existence of a vitamin D autocrine loop in endothelium that may play a role in the development and/or functions of this pathophysiologically significant cell population. Introduction It is well established that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)' is a crucial hormone in Ca2' homeostasis (1). (13) and also is biosynthesized in several ofits peripheral target cells (4-6) in addition to the traditional renal site of formation. Because endothelial cells are a dynamic tissue with spontaneous or injury-dependent cell renewal and expression of specific cell functions at the blood/vessel-wall interface, these cells were examined to determine whether they are potential targets for 1,25(OH)2D3. Initially, the possible presence of specific binding sites for 1,25(OH)2D3 was probed using cultured bovine aortic endothelial cells (BAEC) as a model. When receptors for 1,25(OH)2D3 were observed, the following hypotheses were tested: (a) that the growth state of BAEC may be associated with changes in VDR activity; (b) that BAEC differentiation induced by activators of protein kinase C (PKC) (14-17) may be associated with VDR regulation; (c) that growth parameters of BAEC may be altered in response to 1,25(OH)2D3; (d) that the receptor may be expressed in vivo in endothelial cells in venules and capillaries of human skin; and (e) that BAEC may possess la-hydroxylase activity to form the sterol hormone ligand for the receptor. These studies describe the ...

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In this study, the association of aggressive behavior and personality traits with plasma cortisol levels was investigated in a high-risk community sample of adolescents. Plasma cortisol levels were collected in 245 fifteen-year-olds (118 males, 127 females) from an epidemiological cohort study of children at risk for psychopathology. Additionally, measures of reactive and proactive aggression, externalizing behavior and callous-unemotional together with impulsive personality features were assessed. Both subtypes of aggression as well as delinquent behavior and impulsive personality traits showed significant negative correlations with plasma cortisol levels. This association was observed in males, but not in females. In both gender groups, callous-unemotional traits were unrelated to plasma cortisol levels. This result suggests that the association between cortisol levels and aggression in adolescents is mediated rather by impulsivity than by unemotional or psychopathic traits.

The data suggest that tetrahydroaldosterone is the most reliable screening test for PA. Tetrahydroaldosterone determination in combination with aldosterone-18-glucuronide and free aldosterone increases diagnostic specificity for PA. Potassium, renin, plasma aldosterone, and basal PARR are inadequate screening procedures because they are subject to high rates of false-positive and false-negative results.

The enzyme 11-beta-hydroxysteroid dehydrogenase (11-beta-HSD) regulates glucocorticoid activity by converting cortisol into cortisone and vice versa. Frequent signs of major depression are elevated concentrations of circulating cortisol and ACTH. However, no information is available about the activity of 11-beta-HSD in this disorder. Therefore, we compared diurnal plasma concentrations of cortisol and cortisone and their ratios, reflecting 11-beta-HSD activity, in 25 severely depressed patients (Hamilton Depression Scale, 29 +/- 6; 14 men, 11 women, age 22-77 yr; mean, 47 +/- 16) and 30 control persons (20 men, 10 women age 23-85 yr; mean, 51 +/- 19). Cortisol and cortisone were measured at 0900 h, 1100 h, 1300 h, 2000 h, 2200 h, 0100 h, 0300 h, and 0700 h with specific RIAs after extraction. Both cortisol and cortisone concentrations were significantly increased in patients compared with controls (cortisol, 251.7 +/- 113.1 vs. 160 +/- 96.6 nmol/L; cortisone, 32.8 +/- 10.9 vs. 21.9 +/- 10.9 nmol/L). The calculated ratios of cortisol to cortisone were similar in controls and patients. Similar to cortisol, the circadian variation of cortisone was flattened in patients with the ratio of maximal cortisone to minimal cortisone being 1.9-fold higher in controls than in patients. There was no gender-specific difference in cortisone values neither in patients nor in controls. We conclude that in major depression increased cortisol is not due, at least partly, to an altered 11-beta-HSD activity or to a decrease in cortisone.

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The pathogenesis of pseudohyperaldosteronism from licorice has been evaluated in 6 male volunteers taking daily 7 g of a commercial preparation of licorice for 7 days, corresponding to an intake of 500 mg/day of glycyrrhizic acid. Pseudohyperaldosteronism was evident during the treatment (increase of body weight, suppression of plasma renin activity and plasma aldosterone, reduction of serum potassium). The ratio (tetrahydrocortisol + allo tetrahydrocortisol)/tetrahydrocortisone in urine increased in 5 cases after 3 days of treatment, without an increase of plasma mineralocorticoid activity (PMA). In the 6th case the urinary ratio was unchanged and PMA increased from the pretreatment value. After 7 days of therapy the ratio remained high and PMA was not measurable in 3 cases, while in the other 3 cases the ratio returned to pretreatment and PMA was higher than pretreatment value. We conclude that the pseudohyperaldosteronism from licorice is initially related to decreased activity of 11 beta-hydroxysteroid-dehydrogenase and afterwards also a direct effect of licorice derivatives on mineralocorticoid receptors becomes evident in some cases. In other cases however the effect on the enzyme is prevailing probably due to individual factors.