Seasonal and Sex-Specific Changes in 3β-HSD Activity and Aggressive Behavior

I have previously shown that male Siberian hamsters given a short day (SD)-like melatonin signal (characteristic of the non-breeding season) display increased aggression, have elevated levels of circulating dehydroepiandrosterone (DHEA), and exhibit a decrease in circulating androgen levels following an aggressive interaction (Munley et al. 2020, Hormones and Behavior). Furthermore, I recently determined that SD males exhibit reductions in DHEA, testosterone, and estradiol concentrations in brain regions associated with aggression and that these changes in neurosteroid levels are melatonin-dependent (Munley et al. 2021, Journal of Neuroendocrinology). While my findings suggest that melatonin, adrenal DHEA, and neurosteroids are important in regulating non-breeding aggression, it is unclear what the relative roles of adrenal and neural steroids are in contributing to aggressive behavior and if the importance of these pathways differs between males and females.

The goal of this study is to test whether melatonin facilitates increased non-breeding aggression in male and female Siberian hamsters by upregulating adrenal and neural 3β-hydroxysteroid dehydrogenase (3β-HSD) activity. 3β-HSD is responsible for catalyzing multiple steroidogenic reactions, including: 1) the conversion of pregnenolone to progesterone, and 2) the conversion of DHEA to androstenedione. For this study, I developed a highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) protocol that will allow me to measure the in vitro production of progesterone and androstenedione in the adrenal glands and in discrete brain nuclei. Using this method, I will compare adrenal and neural 3β-HSD activity across seasonal phenotypes and between males and females, and I will assess whether 3β-HSD activity is associated with aggressive behavior in these animals.

This project is being conducted in collaboration with Dr. Jon Trinidad and the Laboratory for Biological Mass Spectrometry at Indiana University.