Allesandra Iadipaolo

Presentation Title

Dynamic endocrine modulation of the proteome in a densely sampled female on and off oral contraceptives

Abstract

Sex steroid hormones are master regulators of many biological processes in humans, including those impacting neuronal survival and plasticity. Rhythmic sex hormone fluctuations (estradiol, progesterone) dynamically modulate brain structure and function across the reproductive cycle. However, the pathways by which fluctuations in sex hormone production modulate neurobiological processes are unclear. In this study, we leveraged cutting-edge proteomic technology to determine the biological impacts of endocrine changes across the menstrual cycle in a single densely sampled individual. In a follow-up study, we examined the proteomic response to suppression of intrinsic sex hormone fluctuations through oral contraceptive (OC) use. Results revealed that over 84% of the proteome was impacted by OC use. Further, we discovered that a diverse set of biological pathways are tied to intrinsic changes in estradiol and progesterone production and are profoundly impacted when typical endocrine rhythms are suppressed. Hormonal suppression is related to altered expression of proteins enriched among immune, inflammatory, and neuroendocrine pathways. Considering emerging evidence of structural brain changes following initiation of OC use, these findings provide new insights into the signaling pathways involved in sex hormones’ neuromodulatory effects.