Haploinsufficiency of steroidogenic factor-1 in mice disrupts adrenal development leading to an impaired stress response

• DOI: 10.1073/pnas.97.26.14488
• Publication Date: 2002-07-26T14:44:19Z
• Authors: Michelle L. Bland; Christina A. M. J...; Susan F. Akana; Stefan R. Bornstein; Graeme Eisenhofer; Mary F. Dallman; Holly A. Ingraham
• Keywords: Haploinsufficiency; Steroidogenic factor 1; Adrenal disorder

Adrenal steroids are essential for homeostasis and survival during severe physiological stress. Analysis of a patient heterozygous the steroidogenic factor-1 (SF-1) gene suggested that reduced expression this nuclear receptor leads to adrenal failure. We therefore examined SF-1 (+/-) mice as potential model delineating mechanisms underlying disease. Here we show +/- exhibit insufficiency resulting from profound defects in development organization. However, compensatory mechanisms, such cellular hypertrophy increased rate-limiting protein StAR, help maintain function at near normal capacity under basal conditions. In contrast, deficits heterozygotes revealed stressful conditions, demonstrating dosage is required mounting an adequate stress response. Our findings predict natural variations leading may underlie some forms subclinical insufficiency, which become life threatening traumatic