Mullerian inhibiting substance

Haqq, C.M., King, C.Y., Ukiyama, E., Falsafi, S., Haqq, T.N., Donahoe, P.K., and Weiss, M.A. (1994) Molecular basis of mammalian sexual determination activation of Mullerian inhibiting substance gene expression by SRY. Science 266, 1494-1500. 

MIS (Mullerian inhibiting substance) or AMH (anti-Mtillerian hormone) Regression of the Mullerian duct... 

Lee MM, Donahoe PK, Silverman BL, Hasegawa T, Hasegawa Y, Gustafson ML, et al. Measurements of serum mullerian inhibiting substance in the evaluation of children with nonpalpable gonads. N Engl J Med 1997 336 1480-6. 

Matias-Guiu X, Pons C, Prat J. Mullerian inhibiting substance, alpha-inhibin, and CD99 expression in sex cord-stromal tumors and endometrioid ovarian carcinomas resembling sex cord-stro-mal tumors. Hum Pathol. 1998 29 840-845. 

Other general cellular responses to Mn(II) include a description by Budzik et al. [216] of Mn(II) participation in the action of Mullerian-inhibiting substance, and the role of Mn(II) in osteosarcoma cell attachment to fibrinogen and von Willebrand factor, mediated by the fibronectin, vitronectin, and adhesion receptors [217]. 

Mullerian Inhibiting Substance (MIS) was the substance of interest. MIS is a glycoslylated protein that normally fosters regression of the ducts in the human embryo. MIS has also been found to promote the regression of ovarian tumor cells hence, some researchers view MIS as a potentially useful chemotherapeutic. However, purifying MIS and then targeting dehvery to a particular location within the body are not easy tasks. 

After the fetal gonads are converted into testes by SRY, testosterone and Miillerian-inhibiting substance (MIS) control subsequent sexual differentiation. MIS causes the regression of the Mullerian duct, which would otherwise develop into female genital tracts. Testosterone promotes the development of the Wolffian duct into male internal genitalia, including epididymis, vas deferens, and seminal vesicles. 

During development, a portion of the mesonephric kidney develops into two different ducts, the Wolffian and Mullerian ducts. The Wolffian duct, under the influence of testosterone, differentiates into the vas deferens, the epididymis, and the seminal vesicle. A second pair of embryonic ducts, the Mullerian ducts, develops alongside the Wolffian ducts. In males, the Mullerian ducts are suppressed due to the action of Miillerian-inhibiting substance (MIS), a hormone secreted by the testes. Maleness depends upon the secretion of testosterone from the testis, and in the absence of testosterone a male will develop a female phenotype. The SRY gene apparently activates the synthesis of MIS, which in turn assures that the Mullerian ducts will atrophy and that the mammal develops as a male. 

But in other large mammals, such as oxen and cattle, chemical crosstalk becomes a problem. When the twin fetuses are of mixed sex, one male and one female, the inevitable result is a reproductively sterile female, known as a freemmtin. Freemartins and their male twins. share the same placenta, and thus they share some of the same hormones that are responsible for sexual development. MuUerian-inhibiting substance, one of the critical hormones in male development, is passed via the placenta from the male twin to its sister, where it interrupts the normal development of the Mullerian ducts into... 

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