The localized activation of circulating glucocorticoids in vivo by the enzyme 11␤-hydroxysteroid dehydrogenase type 1 (11␤-HSD1) plays a critical role in the development of the metabolic syndrome. However, the precise contribution of 11␤-HSD1 in the initiation of adipogenesis by inactive glucocorticoids is not fully understood. 3T3-L1 fibroblasts can be terminally differentiated to mature adipocytes in a glucocorticoid-dependent manner. Both inactive rodent dehydrocorticosterone and human cortisone were able to substitute for the synthetic glucocorticoid dexamethasone in 3T3-L1 adipogenesis, suggesting a potential role for 11␤-HSD1 in these effects. Differentiation of 3T3-L1 cells caused a strong increase in 11␤-HSD1 protein levels, which occurred late in the differentiation protocol. Reduction of 11␤-HSD1 activity in 3T3-L1 fibroblasts, achieved by pharmacological inhibition or adenovirally mediated delivery of short hairpin RNA constructs, specifically blocked the ability of inactive glucocorticoids to drive 3T3-L1 differentiation. However, even modest increases in exogenous 11␤-HSD1 expression in 3T3-L1 fibroblasts, to levels comparable with endogenous 11␤-HSD1 in differentiated 3T3-L1 adipocytes, were sufficient to block adipogenesis. Luciferase reporter assays indicated that overexpressed 11␤-HSD1 was catalyzing the inactivating dehydrogenase reaction, because the ability of both active and inactive glucocorticoids to activate the glucocorticoid receptor were largely suppressed. These results suggest that the temporal regulation of 11␤-HSD1 expression is tightly controlled in 3T3-L1 cells, so as to mediate the initiation of differentiation by inactive glucocorticoids and also to prevent the inhibitory activity of prematurely expressed 11␤-HSD1 during adipogenesis.

We report the case of a 24-year-old female with a history of medullary thyroid carcinoma who presented at 38 weeks gestation with acute chest pain and shortness of breath. She was found to be in pulmonary edema and respiratory failure. An emergency cesarean section was performed. Subsequently, an echocardiogram revealed an ejection fraction of 10%. After medical therapy with digoxin, milrinone, captopril and diuretics, her condition improved rapidly and a repeat echocardiogram showed that the left ventricular function had normalized. Diagnosis of pheochromocytoma was made by urine and plasma catecholamine measurements. Magnetic resonance imaging revealed a 3.7 cm left adrenal mass. Increased uptake activity was seen in the same region by an 131 I-metaiodobenzylguanidine (MIBG) scan. The patient underwent successful surgical resection of the pheochromocytoma. Subsequent DNA analysis revealed that the patient had a mutation of the RET proto-oncogene. The same mutation was also found in several of her family members. In summary, we report a case of multiple endocrine neoplasia 2A presenting as peripartum cardiomyopathy and cardiovascular collapse. Pheochromocytoma should be considered as a potential cause of peripartum cardiomyopathy.European Journal of Endocrinology 151 771-777