FRI287 Pituitary Gene Signatures Link Chronic Systemic Inflammation To Female Reproductive Physiology

Disclosure: C. Garcia: None. L. Velez: None. C. Fox: None. A. Mark: None. K.M. Fisch: None. M.A. Lawson: None. A. Duleba: None. M.M. Seldin: None. D. Nicholas: None. Female reproductive function depends on a perfectly choreographed sequence of hormonal secretion and action, where specific stresses such as inflammation exert profound disruptions. Specifically, LPS-induced inflammation inhibits luteinizing hormone production and secretion from the pituitary, thereby inhibiting downstream production of sex hormones. However, this outcome has only been observed in acute inflammatory stress and little is known about the mechanisms by which chronic inflammation affects reproduction. In this study we seek to understand the chronic effects of LPS on luteinizing hormone secretion and consequent pituitary function. An inflammatory state was induced in female mice using biweekly doses of LPS injections. Surprisingly, luteinizing hormone was not inhibited and instead we found it was increased dose-dependently with LPS treatments. This is consistent with the features of the reproductive disorder polycystic ovary syndrome (PCOS). Here, analysis of bulk RNA-sequencing of mouse pituitary and integration with genetic variation of human pituitary expression profiles revealed pathways that are highly conserved between species. These results provide insights into the impacts of LPS-induced chronic inflammation on reproductive physiology. Presentation: Friday, June 16, 2023