Objectives: Military personnel are required to train and operate in challenging multi-stressor environments, which can affect hormonal levels, and subsequently compromise performance and recovery. The aims of this project were to 1) assess the impact of an eight-day military training exercise on salivary cortisol and testosterone, 2) track the recovery of these hormones during a period of reduced training. Methods: This was a prospective study whereby 30 soldiers (n = 27 men, n = 3 women) undergoing the Australian Army combat engineer ‘Initial Employment Training’ course were recruited and tracked over a 16-day study period which included an eight-day military training exercise. Non-stimulated saliva samples were collected at waking, 30 min post waking, and bedtime on days 1, 5, 9, 13, 15; measures of subjective load were collected on the same days. Sleep was measured continuously via actigraphy, across four sequential study periods; 1) baseline (PRE: days 1–4), 2) field training with total sleep deprivation (EX-FIELD: days 5–8), 3) training at simulated base camp with sleep restriction (EX-BASE: days 9–12), and 4) a three-day recovery period (REC: days 13–15). Results: Morning cortisol concentrations were lower following EX-FIELD (p<0.05) compared to the end of REC. Training in the field diminished testosterone concentrations (p<0.05), but levels recovered within four days. Bedtime testosterone/cortisol ratios decreased following EX-FIELD and did not return to pre-training levels. Conclusions: The sensitivity of testosterone levels and the testosterone/cortisol ratio to the period of field training suggests they may be useful indicators of a soldier’s state of physiological strain, or capacity, however inter-individual differences in response to a multi-stressor environment need to be considered.

The zinc finger transcription factor EGR4 has previously been identified as having a critical role in the proliferation of small cell lung cancer. Here, we have identified a novel, shortened splice variant of this transcription factor (EGR4-S) that is regulated by Heat Shock Factor-1 (HSF1). Our findings demonstrate that the shortened variant (EGR4-S) is upregulated with high EGFR, HER2, and H-Ras^v12-expressing breast cell lines, and its expression is inhibited in response to HER pathway inhibitors. Protein and mRNA analyses of HER2+ human breast tumours indicated the novel EGR4-S splice variant to be preferentially expressed in tumour tissue and not detectable in patient-matched normal tissue. Knockdown of EGR4-S in the HER2-amplified breast cancer cell line SKBR3 reduced cell growth, suggesting that EGR4-S supports the growth of HER2+ tumour cells. In addition to chemical inhibitors of the HER2 pathway, EGR4-S expression was also found to be suppressed by chemical stressors and the overexpression of HSF1. Under these conditions, reduced EGR4-S levels were associated with the observed lower cell growth rate, but the augmentation of properties associated with higher metastatic potential. Taken together, these findings identify EGR4-S as a potential biomarker for HER2 pathway activation in human tumours that is regulated by HSF1.