Cortisol, progesterone, 17α-hydroxyprogesterone, and TSH responses in dogs injected with low-dose lipopolysaccharide.

Background: Stress and diseases such as endotoxemia induce cortisol synthesis through a complex biosynthetic pathway involving intermediates (progesterone, and 17α-hydroxyprogesterone (17α-OHP)) and suppression of the hypothalamus-pituitary-thyroid axis.

Objective: To measure plasma concentrations of cortisol, progesterone, 17α-OHP, and thyroid stimulating hormone (TSH) in dogs experimentally injected with intravenous low-dose lipopolysaccharide (LPS). Our hypothesis was that LPS treatment would elicit a significant increase in cortisol and its precursors, and a significant decrease in TSH concentration.

Methods: Hormone measurements were performed on blood samples left over from a previous investigation (2011) on the effect of low-dose LPS on hematological measurands. Five sexually intact female dogs, none in estrous at the time of the study, were administered saline treatment two weeks prior to LPS treatment. LPS was administered intravenously at a dose of 0.1 µg/kg. Blood was collected before (baseline, time -24 hours) and 3-, 6- and 24-hours post-injection. Mixed model analysis for repeated measures was used, with both treatment and time as the repeated factors. Ranked transformation were applied when diagnostic analysis exhibited violation of normality and equal variance assumptions. Post hoc multiple comparisons were performed with Tukey's adjustment. Statistical significance was defined as  < 0.05.

Results: Significant differences relative to baseline values were detected following both treatments. Compared to baseline, dogs had significantly higher cortisol and 17α-OHP at 3-hours, and significantly lower TSH at 3- and 6-hours following LPS treatment. Dogs had significantly lower TSH at 6- and 24- following saline treatment. Though not statistically significant, the trend in progesterone concentrations was similar to cortisol and 17α-OHP, with an increase at 3-hours post-injection followed by a decrease close to baseline following both LPS and saline. Cortisol and 17α-OHP concentrations were higher after LPS treatment than after saline treatment at 3- and 6-hours post-injection, but differences were not statistically significant, and no significant differences between treatments were detected for any other hormone or timepoint.

Discussion And Conclusion: Cortisol and its adrenal precursors are released in the bloodstream following a low dose of LPS, while TSH appears to decrease. Similar changes occurred following saline treatment, suggesting that even routine handling and saline injection in conditioned dogs can elicit alterations in the internal equilibrium with subsequent modification of both hypothalamus-pituitary-adrenal and thyroid axes. Changes to adrenal and thyroid hormone concentrations must be interpreted in light of clinical information. Further studies are needed to elucidate mechanisms of adrenal steroidal hormone synthesis and secretion in response to various stressful stimuli in both neutered and intact animals.