Mullerian-inhibiting substance type II receptor expression and function inpurified rat Leydig cells

Mullerian-inhibiting substance (MIS), a gonadal hormone in the transforming growth factor-beta superfamily, induces Mullerian duct involution during m ale sexual differentiation. Mice with null mutations of the MIS ligand or r eceptor develop Leydig cell hyperplasia and neoplasia in addition to retain ed Mullerian ducts, whereas MIS-overexpressing transgenic mice have decreas ed testosterone concentrations and Leydig cell numbers. We hypothesized tha t MIS directly modulates Leydig cell proliferation and differentiated funct ion in the maturing testis. Therefore, highly purified rat Leydig and Serto li cells were isolated to examine cell-specific expression, binding, and fu nction of the MIS type II receptor. These studies revealed that this recept or is expressed abundantly in progenitor (21-day) and immature (35-day) Ley dig cells as well as in Sertoli cells. Prepubertal progenitor Leydig cells exhibit high affinity (K-d = 15 nM), saturable binding of MIS. No binding, however, is detected with either peripubertal immature Leydig cells or Sert oli cells at either age. Moreover, progenitor, but not immature Leydig cell s, respond to MIS by decreasing DNA synthesis. These data demonstrate that functional MIS type II receptors are expressed in progenitor Leydig cells a nd support the hypothesis that MIS has a direct role in the regulation of p ostnatal testicular development.