Müllerian inhibiting substance

Müllerian Inhibiting Substance (MIS), also known as Anti-Müllerian Hormone (AMH), is a glycoprotein hormone that plays a crucial role in sexual differentiation during embryonic development. It is a member of the transforming growth factor beta (TGF-β) superfamily.

Structure

MIS is a dimeric glycoprotein composed of two identical subunits linked by disulfide bonds. Each subunit is approximately 70 kDa in size. The protein is encoded by the AMH gene located on chromosome 19 in humans.

Function

MIS is primarily responsible for the regression of the Müllerian ducts in the male embryo. The Müllerian ducts are the precursors to female internal reproductive structures, including the fallopian tubes, uterus, and the upper portion of the vagina.

Role in Male Development

In male embryos, MIS is secreted by the Sertoli cells of the developing testes. The presence of MIS leads to the regression of the Müllerian ducts, preventing the development of female reproductive organs. This process is critical for normal male sexual differentiation.

Role in Female Development

In female embryos, the absence of MIS allows the Müllerian ducts to develop into the female reproductive tract. MIS levels remain low during female development but increase after puberty, where it is produced by the granulosa cells of the ovarian follicles.

Clinical Significance

MIS has several clinical applications, particularly in the fields of reproductive medicine and oncology.

Reproductive Medicine

In females, serum levels of MIS are used as a marker of ovarian reserve. Low levels of MIS can indicate diminished ovarian reserve, which is important in the assessment of fertility.

Oncology

MIS has been investigated for its potential use in the treatment of certain types of cancer, such as ovarian cancer and prostate cancer. Its role in inhibiting the growth of Müllerian-derived tissues makes it a candidate for targeted therapies.

Pathophysiology

Abnormalities in MIS production or function can lead to disorders of sexual development.

Persistent Müllerian Duct Syndrome

This condition occurs in genetic males when there is a deficiency in MIS or its receptor, leading to the presence of both male and female internal reproductive structures. It is characterized by the persistence of Müllerian duct derivatives, such as the uterus and fallopian tubes, in otherwise normal males.

Research Directions

Ongoing research is focused on understanding the molecular mechanisms of MIS action, its role in gonadal development, and its potential therapeutic applications in cancer treatment.

See Also

• Sexual differentiation
• Transforming growth factor beta
• Sertoli cell
• Granulosa cell

External Links

• [Link to relevant medical resources]