Müllerian inhibiting substance contributes to sex-linked biases in the brain and behavior

Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7203-8. doi: 10.1073/pnas.0902253106. Epub 2009 Apr 9.

Abstract

Many behavioral traits and most brain disorders are common to males and females but are more evident in one sex than the other. The control of these subtle sex-linked biases is largely unstudied and has been presumed to mirror that of the highly dimorphic reproductive nuclei. Sexual dimorphism in the reproductive tract is a product of Müllerian inhibiting substance (MIS), as well as the sex steroids. Males with a genetic deficiency in MIS signaling are sexually males, leading to the presumption that MIS is not a neural regulator. We challenge this presumption by reporting that most immature neurons in mice express the MIS-specific receptor (MISRII) and that male Mis(-/-) and Misrii(-/-) mice exhibit subtle feminization of their spinal motor neurons and of their exploratory behavior. Consequently, MIS may be a broad regulator of the subtle sex-linked biases in the nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / metabolism
  • Animals
  • Anti-Mullerian Hormone / deficiency
  • Anti-Mullerian Hormone / genetics
  • Anti-Mullerian Hormone / metabolism*
  • Behavior, Animal / physiology*
  • Brain / embryology
  • Brain / metabolism*
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Developmental
  • Male
  • Mice
  • Mice, Knockout
  • Motor Neurons / cytology
  • Motor Neurons / metabolism
  • Receptors, Peptide / deficiency
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism
  • Receptors, Transforming Growth Factor beta / deficiency
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism
  • Sex Characteristics*
  • Spine / cytology
  • Spine / metabolism

Substances

  • Androgens
  • Receptors, Peptide
  • Receptors, Transforming Growth Factor beta
  • anti-Mullerian hormone receptor
  • Anti-Mullerian Hormone