Intra-pituitary follicle-stimulating hormone signaling regulates hepatic lipid metabolism

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 found 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 novel 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. Overall design: Total RNA from liver tissue was purified by using the RNeasy Plus Mini kit (QIAGEN) according to the manufacturer's instructions. RNA samples with RNA integrity number greater than 8 were used to build RNA-seq libraries. 1000 ng total RNA for each sample was used to build libraries employing the NEB Next Ultra RNA Library preparation kit (Ipswich). The library was sequenced in the Illumina Hiseq2500 platform with 2× 100-bp paired-end reads. After alignment, transcripts with an absolute value of log2 (fold change) larger than 1 and q value below 0.05 were considered to be differentially expressed. Gene Set Enrichment Analysis (GSEA) was performed to functionally study the transcriptomic changes.