Endocrine Abstracts

Background: The hypothalamus-pituitary-adrenal axis (HPA) controls the neuroendocrine response to psychological and physiological stress. The balance of the hormones synthesised and secreted by these organs is tightly regulated. However, there are intrinsic differences in the relative expression of these hormones depending on sex, which can influence the magnitude of the endocrine response to stressors or the response to pharmacological treatments. Herein, we performed a study investigating the stress response, including HPA genes of interest to identify novel pathways differentially regulated in male and female mice, which can be affected during stress.

Methods: mRNA was extracted from the hypothalamus, pituitary and adrenal gland of 30-week-old male and female C56Bl/6J mice for qPCR analyses. Plasma corticosterone concentration was measured using an ELISA kit at baseline and after exposure to stressors, including overnight fasting (16h), exercise to exhaustion and the administration of synthetic ACTH[1-24] (tetracosactrin, Synacthen®).

Results: mRNA studies identified pathways that are differentially regulated between male and female mice, including steroidogenesis, the melanocortin system, gonadotropin-releasing hormone pathway, growth, energy balance and blood pressure regulation. Plasma corticosterone levels increased in both males and females after overnight food withdrawal, exercise and ACTH[1-24] stimulation. However, these responses were larger in female animals.

Conclusion: Herein we identify sex-dependent HPA dimorphism to stress including differential mRNA expression in male compared to female mice as well as enhanced corticosterone responses in females. These findings reinforce the necessity to conduct research studies on both sexes and awareness of stressors applied to ensure consistency of data as well as efficacy and safety of newly developed drugs.