Mullerian inhibiting substance in humans: normal levels from infancy to adulthood

Mary M. Lee, University of Massachusetts Medical School
Patricia K. Donahoe, Massachusetts General Hospital
Tomonobu Hasegawa, Tokyo Metropolitan Kiyose Children's Hospital
Bernard Silverman, Children's Memorial Hospital
Gretchen B. Crist, Massachusetts General Hospital
Sharon Best, Massachusetts General Hospital
Yukihiro Hasegawa, Tokyo Metropolitan Kiyose Children's Hospital
Richard A. Noto, New York Medical College
David Schoenfeld, Massachusetts General Hospital
David T. MacLaughlin, Massachusetts General Hospital

At the time of publication, Mary Lee was not yet affiliated with the University of Massachusetts Medical School.


Mullerian-inhibiting substance (MIS) is a gonadal hormone synthesized by Sertoli cells of the testis and granulosa cells of the ovary. To facilitate the use of MIS for the evaluation of intersex disorders and as a tumor marker in women with MIS-expressing ovarian tumors, we measured MIS in 600 serum samples from males and females. These data show that mean MIS values for males rise rapidly during the first year of life and are highest during late infancy, then gradually decline until puberty. In contrast, MIS values in females are lowest at birth and exhibit a minimal increase throughout the prepubertal years. Whereas MIS is uniformly measurable in all prepubertal boys studied, it is undetectable in most prepubertal female subjects. These data reveal an easily discernible sexually dimorphic pattern of expression and confirm that MIS can be used as a testis-specific marker during infancy and early childhood. MIS values that are above the upper limits for females are discriminatory for the presence of testicular tissue or ovarian tumor, and those below the lower limits for males are consistent with dysgenetic or absent testes or the presence of ovarian tissue. These data will enable normal and abnormal levels of MIS to be differentiated with higher precision and will facilitate the use of MIS in the management of gonadal disorders.