Abstract
Müllerian inhibiting substance type II receptor expression and function in purified rat Leydig cells
Lee,Mary M.; Seah,Ching Ching; Masiakos,Peter T.; Sottas,Chantal M.; Preffer,Frederic I.; Donahoe,Patricia K.; MacLaughlin,David T.; Hardy,Matthew P.
Endocrinology 140(6): 2819-2827
Publication date: 1999
Müllerian-inhibiting substance (MIS), a gonadal hormonein the transforming growth factor-ß superfamily, inducesMüllerian duct involution during male sexual differentiation.Mice with null mutations of the MIS ligand or receptor developLeydig cell hyperplasia and neoplasia in addition to retainedMüllerian ducts, whereas MIS-overexpressing transgenicmice have decreased testosterone concentrations and Leydig cellnumbers. We hypothesized that MIS directly modulates Leydigcell proliferation and differentiated function in the maturingtestis. Therefore, highly purified rat Leydig and Sertoli cellswere isolated to examine cell-specific expression, binding,and function of the MIS type II receptor. These studies revealedthat 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 (K= 15 nM), saturable binding of MIS. No binding, however, isdetected with either peripubertal immature Leydig cells or Sertolicells at either age. Moreover, progenitor, but not immatureLeydig cells, respond to MIS by decreasing DNA synthesis. Thesedata demonstrate that functional MIS type II receptors are expressedin progenitor Leydig cells and support the hypothesis that MIShas a direct role in the regulation of postnatal testicular development.
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