Pediatric Surgery Research Laboratory

In Focus: MIS Production & Fertility Mary E. Fallat, MD Professor & Director Division of Pediatric Surgery

High MIS Levels Linked to Infertility in Men and Women
Müllerian inhibiting substance (MIS) is a hormone produced by the testis and ovary. Once thought to be exclusively a fetal hormone, it is now known that MIS production continues in adults.

MIS and Polycystic Ovary Syndrome
Could MIS play a role in polycystic ovary syndrome (PCOS)? PCOS is the most common cause of infertility in women and is due to an inability to produce normal oocytes. PCOS affects 5-10% of premenopausal women. It is associated with chronic anovulation and an inability to produce normal oocytes, making PCOS one of the most common causes of infertility in women. The etiology of PCOS remains unknown, but studies suggest its cause is related to a complex interaction of hormones, steroids and enzymes. Our studies have shown higher levels of MIS in blood and follicular fluid of women and teenage girls with PCOS compared with normal women.

The increase in MIS production appears to be an early manifestation of the disease. Although the role of MIS in PCOS has yet to be defined, our preliminary studies show that MIS may suppress the synthesis of the enzyme CYP19, which is essential for the production of estradiol by the ovary. Normal oocyte development and growth are dependent on adequate and timely production of estradiol by the ovary. We are currently studying the mechanism of action of MIS on CYP19 gene expression.

In animal studies, treatment with MIS in vivo leads to a reduction in testosterone synthesis by down-regulation of expression of cytochrome P450c17 hydroxylase/lyase (CYP17), the enzyme that catalyzes the committed step in androgen synthesis. However, in PCOS, ovarian production of both MIS and testosterone are elevated. This is incongruous with the concept that MIS negatively influences testosterone production. The relationship between MIS and testosterone in the human ovary has not been defined and the cause of increased MIS production in PCOS is unknown. Our goals are to determine what causes an increase in MIS production in PCOS, and to examine the relationship between MIS and testosterone in this disease.

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