Spinal Cord Injury Acutely Alters Diurnal Testosterone Secretion in Male Rats

Abstract

BackgroundHealthy young adult men and male Sprague‐Dawley rats both exhibit diurnal variations in testosterone (T) secretion. Spinal cord injury (SCI) has been shown to decrease serum T concentrations in men compared to age‐matched healthy persons, with lower T concentrations correlated to more recent and more severe injury.PurposeTo determine if recent SCI alters the diurnal variation in T secretion in a rodent severe contusion SCI model.Methods17‐wk‐old male Sprague‐Dawley (SD) rats were matched on body mass and stratified to receive T9 laminectomy (SHAM surgery, N=4) or severe (250 kilodyne) T9 contusion SCI (N=6) via computer‐controlled impactor. Tail blood was acquired every 2‐h during daytime hours (7am–5pm) at baseline (1‐wk pre‐surgery), 3‐d post‐surgery, and 7‐d post‐surgery, with serum T evaluated via ELISA. SAS JMP was used to assess changes in T over time via repeated measures ANOVA and differences between individual time points via one‐way ANOVA with non‐parametric Wilcoxon post‐hoc testing (significance at p<0.05). T concentrations are reported as means ± standard deviation in ng/ml.ResultsBaseline T concentrations averaged 3.36 ± 2.22, with minimal non‐significant changes occurring across daytime hours. T secretion did not change after SHAM surgery, except for a decrease at 5pm on 3‐d post‐surgery vs the respective baseline time point (0.61 ± 0.17 vs. 2.96 ± 1.67 respectively; 80% decline). Serum T reverted to baseline at 7‐d post‐surgery in SHAMs, with no differences in daytime T area under the curve (AUC) values present at any time point. SCI produced 60–90% lower serum T at all 3‐d post‐SCI time points vs baseline and T remained 70–85% lower than baseline between 7–11am at 7‐d post‐SCI, while afternoon T was similar to baseline concentrations. Daytime T AUC values for SCI animals were 37.8 ± 15.2 (baseline), 7.4 ± 4.6 (3‐d post‐SCI), and 12.9 ± 4.0 (7‐d post‐SCI), with 3‐d and 7‐d AUC values approaching significance vs baseline (p=0.06 for both).ConclusionSham surgery did not influence serum T concentrations and did not appear to alter diurnal T secretion. In comparison, serum T was dramatically suppressed during daytime hours at 3‐d post‐SCI and remained suppressed at 7‐d post‐SCI only during the morning hours, indicating disruption of normal diurnal T secretion. The mediators of suppressed T after SCI remain to be elucidated, but may involve reduced gonadotropin releasing hormone (GnRH) and/or leuteinizing hormone (LH) secretion, impaired splanchnic innervation that may interfere with LH receptor regulation, reduced gonadal blood flow that may alter LH delivery to the testes, and/or disruption of neural pathways between the central nervous system and the testes that regulate Leydig cell function independently of the anterior pituitary.Support or Funding InformationThis work was supported by the Presidential Early Career Award to Scientists and Engineers (PECASE) #B9290‐O to JFY from the White House Office of Science and Technology Policy and VA Rehabilitation R&D Service.Serum testosterone at "B" baseline (1 week pre‐SCI), "3D" (3 days post‐SCI), and "7D" (7 days post‐SCI). 17 week old (n=6) male Sprague‐Dawley rats had significantly lower (p<0.05) serum testosterone at 3D and 7D post‐SCI. * indicates sig. less than baseline. Cross bars indicate median and inter‐quartile range.Figure 1