Clinical applications of Mullerian inhibiting substance in patients with gonadal disorders

Mullerian inhibiting substance (MIS) is a gonadal peptide produced uniquely by Sertoli cells of the testis and granulosa cells of the ovary. In boys, serum MIS is low at birth, increases rapidly during the first year of life, then slowly declines thereafter until puberty. In girls, MIS is undetectable at birth, then rises minimally throughout childhood to a low pubertal peak. As a gonad-specific hormone with a sexually dimorphic pattern of expression, MIS has been recognized as having clinical applications that are relevant to the human reproductive system. Measurement of MIS in children with nonpalpable gonads and/or intersex disorders can help identify testicular tissue and assess testicular function. This is useful for the management of boys with cryptorchidism and for the diagnostic evaluation of children with intersex conditions. Moreover, the secretion of MIS by many sex-cord stromal tumors makes MIS determination beneficial for evaluating the completeness of surgical resection and for longitudinal screening of tumor recurrence in women with sex-cord tumors. MIS immunohistochemistry also may aid in the histologic diagnosis of ovarian tumors when conventional histology is ambiguous. Potential therapeutic uses of MIS that currently are being explored are based on employing its antiproliferative properties for chemotherapy of responsive tumors.