Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism in mice
Sen Qiao, Samer Alasmi, Amanda Wyatt, Philipp Wartenberg, Hongmei Wang, Michael Candlish, Debajyoti Das, Mari Aoki, Ramona Grünewald, Ziyue Zhou, Xiao Yu Tian, Qiang Yu, Viktoria Götz, Anouar Belkacemi, Ahsan Raza, Fabien Ectors, Kathrin Kattler, Gilles Gasparoni, Jörn Walter, Peter Lipp, Patrice Mollard, Daniel J. Bernard, Ersin Karataylı, Senem Ceren Karataylı, Frank Lammert, Ulrich Boehm
Abstract
Inter-organ communication is a major hallmark of health and is often orchestrated by hormones released by the anterior pituitary gland. Pituitary gonadotropes secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to regulate gonadal function and control fertility. Whether FSH and LH also act on organs other than the gonads is debated. Here, we find that gonadotrope depletion in adult female mice triggers profound hypogonadism, obesity, glucose intolerance, fatty liver, and bone loss. The absence of sex steroids precipitates these phenotypes, with the notable exception of fatty liver, which results from ovary-independent actions of FSH. We uncover paracrine FSH action on pituitary corticotropes as a mechanism to restrain the production of corticosterone and prevent hepatic steatosis. Our data demonstrate that functional communication of two distinct hormone-secreting cell populations in the pituitary regulates hepatic lipid metabolism.