Disturbed glucocorticoid receptor autoregulation and corticotropin response to dexamethasone in depressives pretreated with metyrapone.

We studied glucocorticoid receptor autoregulation and corticotropin response to dexamethasone in depressed patients and controls, attempting to control for the confounding effect of endogenous glucocorticoids. After depletion of endogenous cortisol, depressed patients showed an attenuated suppressibility of corticotropin by dexamethasone in the face of unchanged dexamethasone plasma levels. Beta-endorphin levels were strongly correlated with adrenocorticotropic hormone (ACTH) concentrations. Although metyrapone administration resulted in a marked rise of glucocorticoid receptor sites per cell in controls, this effect was not present in depressives. These data support the hypothesis of a decreased glucocorticoid receptor plasticity and a partial steroid resistance in depression.

Characterization of Glucocorticoid Binding Capacity in Human Mononuclear Lymphocytes: Increase by Metyrapone is Prevented by Dexamethasone Pretreatment.

Abstract Autoregulation of receptor systems by their own ligands is a well established biological phenomenon. While down-regulation of the glucocorticoid binding capacity by glucocorticoids has been shown in animals and humans, data on up-regulation processes in humans are lacking. To further explore glucocorticoid receptor plasticity in relation to endogenous ligands, glucocorticoid binding parameters were assessed in 15 healthy controls before and after oral administration of 1.5 g metyrapone with and without dexamethasone pretreatment. Administration of metyrapone resulted in blockade of the feedback of the hypothalamic-pituitary-adrenal system as shown by the rise in adrenocorticotropin levels, while pretreatment with 1 mg dexamethasone completely suppressed adrenocorticotropin concentrations. Glucocorticoid binding sites per lymphocyte exhibited an increase of 63% following metyrapone administration, which was prevented by dexamethasone pretreatment. Comparison of morning and afternoon glucocorticoid binding sites per cell in 11 healthy volunteers further revealed a diurnal rhythm of glucocorticoid receptor sites. These data suggest that human lymphocyte glucocorticoid receptors are under autoregulatory control.

Lymphocyte glucocorticoid receptor binding during depression and after clinical recovery.

Lymphocyte glucocorticoid receptor binding parameters were studied in 15 severely depressed patients during depression and after clinical recovery, and in 15 healthy controls. There was no difference in glucocorticoid receptor number or affinity between depressed patients and recovered or control subjects. Afternoon ACTH and cortisol concentrations did not differ significantly between the three groups. No relationship could be established between glucocorticoid receptor binding and antidepressant medication. These data support the view of an impaired ligand-induced plasticity of glucocorticoid receptor regulation rather than the hypothesis of decreased glucocorticoid receptor numbers during depression.

[The course of functional psychoses (author's transl)]. / Verlaufsdarstellung von Funktionspsychosen.

Functional psychoses correspond to a universal reduction of mental and intellectual function which, fundamentally reversible and unspecific, appear as sequelae of disturbances of cerebral function. They are the most common psychoses in medical practice and in hospitals. With the Syndrome Short Test and Functional Psychosis Scale B we now have a mutually equilibrated test system for the measurement of the whole range of severity of functional psychoses. With these two psychopathometric methods a relatively differentiated investigation of cross section and course can be performed, for example in arriving at a diagnosis, checking medical measures, monitoring the effect of drugs and in the prognosis of a disease.

[Heavy diarrhea by low malignant B cell lymphoma]. / Schwere Durchfälle bei niedrig malignem B-Zell-Lymphom.

A 52-year old female presented with a low, malignant centroblastic-centrocytic lymphoma. After splenectomy and under steroid therapy it came to the eruption of a latent Strongyloides stercoralis infection, which the patient had presumably been suffering from for several years. Due to the immunodeficient condition and under continued steroid therapy even three courses of high dose anthelmintic therapy could not eradicate the parasites. The patient died of fulminant sepsis.