Steroid receptor coactivator-2 expression in brain and physical associations with steroid receptors.

Estradiol and progesterone bind to their respective receptors in the hypothalamus and hippocampus to influence a variety of behavioral and physiological functions, including reproduction and cognition. Work from our lab and others has shown that the nuclear receptor coactivators, steroid receptor coactivator-1 (SRC-1) and SRC-2, are essential for efficient estrogen receptor (ER) and progestin receptor (PR) transcriptional activity in brain and for hormone-dependent behaviors. While the expression of SRC-1 in brain has been studied extensively, little is known about the expression of SRC-2 in brain. In the present studies, we found that SRC-2 was highly expressed throughout the hippocampus, amygdala and hypothalamus, including the medial preoptic area (MPOA), ventral medial nucleus (VMN), arcuate nucleus (ARC), bed nucleus of the stria terminalis, supraoptic nucleus and suprachiasmatic nucleus. In order for coactivators to function with steroid receptors, they must be expressed in the same cells. Indeed, SRC-2 and ER(alpha) were coexpressed in many cells in the MPOA, VMN and ARC, all brain regions known to be involved in female reproductive behavior and physiology. While in vitro studies indicate that SRC-2 physically associates with ER and PR, very little is known about receptor-coactivator interactions in brain. Therefore, we used pull-down assays to test the hypotheses that SRC-2 from hypothalamic and hippocampal tissue physically associate with ER and PR subtypes in a ligand-dependent manner. SRC-2 from both brain regions interacted with ER(alpha) bound to agonist, but not in the absence of ligand or in the presence of the selective ER modulator, tamoxifen. Analysis by mass spectrometry confirmed these ligand-dependent interactions between ER(alpha) and SRC-2 from brain. In dramatic contrast, SRC-2 from brain showed little to no interaction with ERbeta. Interestingly, SRC-2 from both brain regions interacted with PR-B, but not PR-A, in a ligand-dependent manner. Taken together, these findings reveal that SRC-2 is expressed in brain regions known to mediate a variety of steroid-dependent functions. Furthermore, SRC-2 is expressed in many ER(alpha) containing cells in the hypothalamus. Finally, SRC-2 from brain interacts with ER and PR in a subtype-specific manner, which may contribute to the functional differences of these steroid receptor subtypes in brain.

5196 mandible fractures among 4381 active duty army soldiers, 1980 to 1998.

OBJECTIVE: We present the frequencies of various types of mandibular fractures along with associated mechanisms and injuries. METHODS: Retrospective analysis of 5196 mandible fractures in 4381 patients extracted from the Total Army Injury and Health Outcomes Database (TAIHOD), a comprehensive database developed by the U.S. Army Research Institute of Environmental Medicine (USARIEM) that links population data to all hospitalizations among active duty army soldiers. The database is based on the ICD-9 CM coding system. RESULTS: We found the following frequencies for specific mandible fracture locations: angle 35.6%, symphysis 20.1%, subcondylar 14.2%, body 12.7%, condylar process 9.1%, ramus 4.5%, alveolar border 2.7%, and coronoid process 1%. The mechanisms of injury were separated into seven categories. Fighting accounts for 36.2%, automobile accidents for 18.6%, athletics for 13.6%, falls for 9.7%, motorcycle accidents for 3.1%, other land transport accidents for 3%, and miscellaneous causes for 15.8%. A few fracture locations appear to be associated with specific mechanisms. Of 82 alveolar border fractures with known mechanisms, 37% resulted from automobile accidents. Of 1094 angle fractures with known mechanisms, 48.6% resulted from fighting. Our data show that the majority of fractures were isolated to one location. Only one fracture was recorded for 70.6%, 29.2% have two fractures recorded, 0.2% have three or more fractures recorded. Associated injuries were common and include facial lacerations 1236 (28.2%), non-mandible facial bone fractures 733 (16.7%), intracranial injury 403(9.2%), internal injuries 229 (5.2%), fractures of the upper limb 295 (6.7%), fractures of the lower extremity 302 (6.9%), and cervical fractures 34 (0.8%). CONCLUSIONS: The mechanism of injury is important in determining the most likely resultant mandible fracture in the case of angle of mandible and alveolar ridge fractures. The clinician should maintain a high level of suspicion for associated injuries that occur more than one fourth of the time and even more frequently in motor vehicle accident victims. Associated intracranial injury is particularly important to rule out. Associated facial fractures, intracranial injury, internal injuries, and extremity injuries are all more common than cervical fractures.