title: Müllerian-inhibiting substance type II receptor expression and function in purified rat Leydig cells.
abstract: Müllerian-inhibiting substance (MIS), a gonadal hormone in the transforming growth factor-beta superfamily, induces Müllerian duct involution during male sexual differentiation. Mice with null mutations of the MIS ligand or receptor develop Leydig cell hyperplasia and neoplasia in addition to retained Müllerian ducts, whereas MIS-overexpressing transgenic mice have decreased testosterone concentrations and Leydig cell numbers. We hypothesized that MIS directly modulates Leydig cell proliferation and differentiated function in the maturing testis. Therefore, highly purified rat Leydig and Sertoli cells were isolated to examine cell-specific expression, binding, and function of the MIS type II receptor. These studies revealed that this receptor is expressed abundantly in progenitor (21-day) and immature (35-day) Leydig cells as well as in Sertoli cells. Prepubertal progenitor Leydig cells exhibit high affinity (Kd = 15 nM), saturable binding of MIS. No binding, however, is detected with either peripubertal immature Leydig cells or Sertoli cells at either age. Moreover, progenitor, but not immature Leydig cells, respond to MIS by decreasing DNA synthesis. These data demonstrate that functional MIS type II receptors are expressed in progenitor Leydig cells and support the hypothesis that MIS has a direct role in the regulation of postnatal testicular development.
authors.affiliation: The Pediatric Endocrine Unit, Massachusetts General Hospital, Boston 02114, USA. mlee@helix.mgh.harvard.edu
authors.forename: M M
authors.initials: MM
authors.lastname: Lee
authors.forename: C C
authors.initials: CC
authors.lastname: Seah
authors.forename: P T
authors.initials: PT
authors.lastname: Masiakos
authors.forename: C M
authors.initials: CM
authors.lastname: Sottas
authors.forename: F I
authors.initials: FI
authors.lastname: Preffer
authors.forename: P K
authors.initials: PK
authors.lastname: Donahoe
authors.forename: D T
authors.initials: DT
authors.lastname: Maclaughlin
authors.forename: M P
authors.initials: MP
authors.lastname: Hardy
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006023:Glycoproteins; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology; D007985:Leydig Cells / Q000737:chemistry*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018000:Receptors, Peptide / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta; D013735:Testicular Hormones / Q000378:metabolism / Q000494:pharmacology
chemical_list: D006023:Glycoproteins; D006131:Growth Inhibitors; D012333:RNA, Messenger; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D013735:Testicular Hormones; C084621:anti-Mullerian hormone receptor; D054304:Anti-Mullerian Hormone; D004247:DNA