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Follicle-stimulating hormone (FSH) is a gonadotropin released from the pituitary essential for the regulation of folliculogenesis in vertebrates. Unlike mammals, the regulatory mechanism of FSH is unknown in teleosts because gonadotropin-releasing hormone (GnRH) was proven to be dispensable for FSH function. Here, we aimed to identify the FSH-releasing hormone (FSH-RH) by using a model teleost, medaka. We found that knockout of either cholecystokinin receptor, cckbr1, which is highly expressed in the FSH cells, or its ligand cholecystokinin (ccka/cckb), which is expressed in the pituitary projecting neurons, drastically reduced the fshb mRNA expression in the pituitary, resulting in infertility. Also, in vitro experiments clearly demonstrated that cholecystokinin peptide increases [Ca 2+] i of FSH cells and fshb expression. We hypothesize that this system constitutes the long-missing FSH-RH in teleosts.