Mullerian Inhibiting Substance Activity in the Development of the Reproductive Tract and Lung in the Fetus and Control of Oocyte Meiosis in the Adult

Abstract

The development of the normal reproductive tract in male embryos is the result of a series of carefully orchestrated anabolic and catabolic events that for the purposes of this discussion, center about the differentiation of the primitive gonad to a testis. This critical process, presumably directed by the testis-determining factor gene(s) (1–2) results, ultimately, in the ability of the gonad to produce two major testicular hormones: testosterone and mullerian inhibiting substance (MIS). It is the activity of these two factors, acting in concert, to direct the maturation of the male reproductive tract from the wolffian duct system and to cause the regression of the female reproductive tract anlage, the mullerian duct. A variety of studies have shown that once the genetic sex of the gonad is established as testicular, MIS, synthesized and secreted by the Sertoli cells, is responsible for mullerian duct regression (3–4). Testosterone can facilitate this activity of MIS, but cannot, on its own, direct this important event in the development of the male phenotype. Although the fetal ovary does not produce MIS, it has recently been shown that the granulosa cells of the young and adult ovary synthesize and secrete bioactive MIS (5–8). The role of MIS in the female is, obviously, quite different from the major role played by MIS in the male, namely, the regression of the mullerian duct. Our evidence points to MIS as an inhibitor of oocyte meiosis, thus contributing to the proper development of mature germ cells (9).