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 baseline serum dehydroepiandrosterone (DHEA), and increase the metabolism of circulating androgens in response to an aggressive interaction (Munley et al. 2020, Hormones and Behavior).  Our lab has also shown that in vitro melatonin administration elevates DHEA secretion from cultured adrenals in SD females, but not in females housed in long-day photoperiods (Rendon et al. 2015, Proceedings of the Royal Society B). While these findings suggest that hamsters elevate DHEA levels in circulation during SDs, it is unclear how melatonin acts locally to influence adrenal steroidogenesis and, ultimately, increase non-breeding aggression.

DHEA is synthesized in the adrenal cortex via the enzyme CYP17A1 and can be converted to more potent androgens, such as androstenedione (AE) and T, via the steroidogenic enzymes 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-HSD, respectively. Thus, melatonin may mediates SD increases in aggression by upregulating 3β-HSD activity in a tissue-specific manner. The goal of this study is to test whether melatonin signaling induces increased non-breeding aggression in male and female Siberian hamsters by upregulating adrenal and neural 3β-HSD activityBecause 3β-HSD is responsible for catalyzing two separate steroidogenic reactions: the conversion of pregnenolone to progesterone and the conversion of DHEA to AE, this study will allow me to compare DHEA synthesis and metabolism both within and across tissues. For this study, I am developing a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) protocol that allows me to detect minute changes in the concentration of these steroids within tissues and, thus, quantify 3β-HSD activity in the adrenal glands and in discrete nuclei of the brain.

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