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Selective depletion of the Foxo1 and Foxo3 genes in granulosa cells of mice reveals a novel ovarian-pituitary endocrine feedback loop characterized by: 1) undetectable levels of serum FSH but not LH, 2) reduced expression of the pituitary Fshb gene and its transcriptional regulators, and 3) ovarian production of a factor(s) that suppresses pituitary cell Fshb expression. Equally notable, and independent of FSH, microarray analyses and quantitative PCR document that depletion of Foxo1\/3 alters the expression of specific genes associated with follicle growth vs. apoptosis by disrupting critical and selective regulatory interactions of FOXO1\/3 with the activin or bone morphogenetic protein 2 (BMP2) pathways, respectively. As a consequence, both granulosa cell proliferation and apoptosis were decreased. These data provide the first evidence that FOXO1\/3 divergently regulate follicle growth or death by interacting with the activin or BMP pathways in granulosa cells and by modulating pituitary FSH production.<\/jats:p>","DOI":"10.1210\/me.2012-1296","type":"journal-article","created":{"date-parts":[[2013,1,16]],"date-time":"2013-01-16T05:50:29Z","timestamp":1358315429000},"page":"238-252","source":"Crossref","is-referenced-by-count":93,"title":["FOXO1\/3 Depletion in Granulosa Cells Alters Follicle Growth, Death and Regulation of Pituitary FSH"],"prefix":"10.1210","volume":"27","author":[{"given":"Zhilin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology (Z.L., J.S.R.),University of Texas Southwestern Medical Center, Dallas Texas 75390"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego H.","family":"Castrillon","sequence":"additional","affiliation":[{"name":"Department of Pathology (D.H.C.), University of Texas 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