Regulation of corticosteroid receptors in patients with anorexia nervosa and Cushing’s syndrome D Armanini, P Spinella 1 , M Simoncini, A Basso 3 , S Zovato, G B Pozzan 2 , C B De Palo, G Bucciante 2 and I Karbowiak 4 Istituto Semeiotica Medica, 1 Cattedra Nutrizione Clinica and 2 Dipartimento di Pediatria, University of Padua, 3 Divisione Malattie del Ricambio, Ospedale S Bortolo Vicenza and 4 Laboratorio Analisi, Ospedale Piove di Sacco, Padua, Italy (Requests for offprints should be addressed to D Armanini, Istituto di Semeiotica Medica, University of Padua, Via Ospedale 105, 35100 Padua, Italy) Abstract We have studied 16 patients with anorexia nervosa (11 with a stabilised weight loss and 5 in the weight-losing phase), 11 healthy controls, and 10 patients with Cushing’s syndrome, by measuring plasma cortisol (by enzyme- immunoassay), ACTH (by RIA), corticosteroid (Type I-mineralocorticoid and Type II-glucocorticoid) receptors in mononuclear leukocytes (by radio-receptor assay), and lymphocyte subpopulations (by cytofluorimetry). In anorexic patients with a stabilised weight loss and in Cushing’s syndrome the mean value of both Type I and Type II corticosteroid receptors in mononuclear leuko- cytes was significantly lower than in controls. The corre- lation between Type II receptors and plasma cortisol was inverse in stabilised anorexia nervosa and in Cushing’s syndrome, and direct in healthy controls. Anorexic patients in the weight-losing phase showed a significant increase in plasma cortisol levels and a normal number of Type II receptors. From these results we hypothesise that in anorexia nervosa there is a progression from an increase in plasma cortisol in the weight-losing phase, to a concomitant decrease in Type II receptors when the disease is stabilised. Journal of Endocrinology (1998) 158, 435–439 Introduction Anorexia nervosa and Cushing’s syndrome are associated with increased levels of plasma cortisol (Walsh et al. 1987, Vierhapper et al. 1990). A common pattern is also the frequent lack of response to an overnight dexamethasone suppression test (Walsh et al. 1987, Vierhapper et al. 1990, Seeman & Robbins 1994). The effects of cortisol are mediated by binding to corticosteroid receptors at the level of target tissues. The corticosteroid receptors are of two types, Type I and Type II (Funder et al. 1988, Funder 1996). Type I receptors are bound by aldosterone in tissues in which cortisol is inactivated to cortisone by the Type II 11-hydroxysteroid dehydrogenase (Funder 1996), while in other tissues which lack the enzyme, as for example in the rat hippocampus, Type I receptors act as gluco- corticoid receptors, being bound by cortisol, and are also involved in the regulation of corticotrophin-releasing factor–adrenocorticotrophin (ACTH)–cortisol feedback (Bradbury et al. 1991). Type I receptors are also targets for mineralocorticoids in non-classical target tissues for aldo- sterone when cortisol and/or aldosterone are increased (Wehling et al. 1987). Type II receptors do respond to higher concentrations of cortisol such as those early in the morning or during stress (Bradbury et al. 1991). A con- tinuous occupancy of corticosteroid receptors results in excessive activity of steroid-responsive genes despite the capacity for a down-regulation of the receptors which can blunt the effector mechanism itself (Bradbury et al. 1991). The brain corticosteroid receptors are inaccessible in the clinical population, therefore the study of corticosteroid receptors in humans must be indirect. In the adrenal- ectomised rat the regulation of corticosteroid receptors is similar in lymphoid tissue and hippocampus (Lowy 1991), supporting the utilisation of mononuclear leukocytes (MNL) as an index of the regulation of corticosteroid receptors at the supra-hypothalamic level in humans. In a previous study we have characterised Type I receptors in MNL (Armanini et al. 1985a) and have found an equal amount of Type I and Type II receptors in T- and B-lymphocytes (Armanini et al. 1988). The increased cortisol in anorexia nervosa is not associated with clinical symptoms of hypercortisolism and the number of Type II receptors was found to be normal (Girardin et al. 1991) or reduced (Kontula et al. 1982) in these patients. We have evaluated the corticosteroid Type I and Type II receptors in MNL and lymphocyte subpopulations in patients with anorexia nervosa and Cushing’s syndrome, a clinical situation where the effector mechanism of cortisol is clearly increased. The evaluation of lymphocyte subpopulations could provide some information on the lymphoid system changes in hypercortisolism. It has been shown that oral 435 Journal of Endocrinology (1998) 158, 435–439  1998 Society for Endocrinology Printed in Great Britain 0022–0795/98/0158–0435 $08.00/0