Primary pigmented nodular adrenocortical disease: paradoxical responses of cortisol secretion to dexamethasone occur in vitro and are associated with increased expression of the glucocorticoid receptor.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent adrenal Cushing's syndrome (CS), which is often associated with Carney complex (CNC). We have recently described a paradoxical increase in cortisol excretion after dexamethasone administration in most patients with PPNAD. In the present study we investigated the hypothesis that this phenomenon is due to a primary abnormality of the tissues affected by PPNAD, rather than a defect of the patients' hypothalamic-pituitary-adrenal axis; as such it should be replicated in vitro by adrenal slices exposed directly to dexamethasone.

Glucocorticoids inhibit bone resorption by isolated rat osteoclasts by enhancing apoptosis.

We have studied the effects of glucocorticoids on the activity and viability of neonatal rat osteoclasts in vitro. In the bone slice assay, glucocorticoids caused a dose-dependent decrease in the amount of bone resorbed, which was accompanied by a parallel decrease in osteoclast number. Loss of osteoclasts was due to their death, which occurred by the process of apoptosis.

Low molecular weight components but not dimeric HCG inhibit growth and down-regulate AP-1 transcription factor in Kaposi's sarcoma cells.

Kaposi's sarcoma, a sexually dimorphic disease inflicting high mortality in AIDS, remains at present without effective treatment. A recent report (Nature 375:64, 1995) showed that the placental glycoprotein hormone, human chorionic gonadotropin (HCG), and surprisingly its beta subunit, inhibit tumorigenicity and metastasis of Kaposi's sarcoma cells in mice xenografts. The anti-KS efficacy of a commercial HCG was subsequently demonstrated in clinical trials.

Expression and cytokine regulation of glucocorticoid receptors in Kaposi's sarcoma.

Development of Kaposi's sarcoma (KS) after glucocorticoid therapy has been observed in a variety of clinical states including human immunodeficiency virus-1 infection and recent in vitro studies provided evidence for a direct stimulation effect of glucocorticoid hormones on KS cell proliferation. The importance of glucocorticoids in KS pathogenesis is further highlighted by the finding that glucocorticoids synergize with cytokines to promote acquired immune deficiency syndrome (AIDS)-associated KS (AIDS-KS) growth. Furthermore, cytokine effects were abrogated by the glucocorticoid antagonist RU-486.