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• W2890610675 endingPage "1167" @default.
• W2890610675 startingPage "1156" @default.
• W2890610675 abstract "Extensive pre-clinical studies suggest that sex steroids are neuroprotective in experimental traumatic brain injury (TBI). However, clinical trials involving sex hormone administration have not shown beneficial results, and our observational cohort studies show systemic estradiol (E2) production to be associated with adverse outcomes. Systemic E2 is produced via aromatization of testosterone (T) or reduction of estrone (E1). E1, also produced via aromatization of androstenedione (Andro) and is a marker of T-independent E2 production. We hypothesized that E1 would be (1) associated with TBI-related mortality, (2) the primary intermediate for E2 production, and (3) associated with adipose tissue-specific aromatase transcription. We assessed 100 subjects with severe TBI and 8 healthy controls. Serum levels were measured on days 0–3 post-TBI for key steroidogenic precursors (progesterone), aromatase pathway intermediates (E1, E2, T, Andro), and the adipose tissue-specific aromatase transcription factors cortisol, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). E1 was elevated after TBI versus controls. High E1 was associated with higher progesterone, cortisol, and IL-6 (p < 0.05). Multivariable logistic regression demonstrated that those in the highest E1 tertile had increased odds for mortality (adjusted OR = 5.656, 95% CI = 1.102–29.045, p = 0.038). Structural equation models show that early serum E2 production is largely T independent, occurring predominantly through E1 metabolism. Acute serum E1 functions as a mortality marker for TBI through aromatase-dependent E1 production and T-independent E2 production. Further work should evaluate risk factors for high E2 production and how systemic E2 and its key intermediate E1 contribute to the extracerebral consequences of severe TBI." @default.
• W2890610675 created "2018-09-27" @default.
• W2890610675 creator A5010057699 @default.
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• W2890610675 creator A5073866367 @default.
• W2890610675 creator A5080778824 @default.
• W2890610675 date "2019-04-01" @default.
• W2890610675 modified "2023-10-02" @default.
• W2890610675 title "Systemic Estrone Production and Injury-Induced Sex Hormone Steroidogenesis after Severe Traumatic Brain Injury: A Prognostic Indicator of Traumatic Brain Injury-Related Mortality" @default.
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