HIGHLIGHTED TOPIC A Physiological Systems Approach to Human and Mammalian Thermoregulation Heat intolerance: does gene transcription contribute?

Moran, Daniel S., Luba Eli-Berchoer, Yuval Heled, Liran Mendel, Mara Schocina, and Michal Horowitz. Heat intolerance: does gene transcription contribute? J Appl Physiol 100: 1370–1376, 2006. First published December 15, 2005; doi:10.1152/japplphysiol.01261.2005.— During exertion in the heat, heat-intolerant (HI) subjects have a physiological disability in metabolic heat dissipation. The HI state is either permanent or temporary, depending on whether it stems from transient predisposing factors or inherent thermoregulatory dysfunction. In this investigation, we studied protein levels of heat shock protein (HSP) 70 and HSP72, HSP90, bcl-2xL, glutathione S-transferase-p, heat shock factor-1, TATA-binding protein-associated factor, and NFB transcripts using Western blot and quantitative RTPCR, respectively, in lymphocytes of HI and tolerant (T) male volunteers of similar anthropometric features. Measurements were made from blood drawn before, during the heat tolerance test (3.5 mph, 40°C, 40% relative humidity, 2 h), and 1 h after recovery at 24°C. Rectal and skin temperatures, as well as heart rate, were continuously recorded. Of 58 subjects, 7 were identified as HI, with a significantly higher physiological strain index than in the T group (6.3 0.9 vs. 3.8 0.6, P 0.001). The responsiveness of the vasculature to thermal stimuli was decreased in the HI group, as indicated by rectal temperature minus skin temperature. The HSP72 level in the HI group dropped during the recovery session (P 0.01), whereas that of the T group continued to rise. A significantly increased expression of the transcription factors in the T subjects and significantly decreased expression in the HI group (P 0.009, 0.013, and 0.005 for heat shock factor-1, NFB, and TATA-binding proteinassociated factor, respectively) points to impaired transcriptional processes in the HI group. Our data suggest that transcriptional malfunction and sluggishness of the vasculature to thermal stimuli are predisposing factors in the HI group.