Developmental expression of a candidate müllerian inhibiting substance type II receptor.

Abstract

We have isolated a candidate Müllerian inhibiting substance (MIS) type II receptor complementary DNA from an embryonic rat urogenital ridge library and have studied its binding to MIS, its developmental pattern of expression and tissue distribution. By in situ hybridization with a full-length riboprobe, the receptor is expressed in the mesenchymal cells surrounding the Müllerian duct at embryonic days 14, 15, and 16 and in tubular and follicular structures of the rat fetal gonads. Expression of the messenger RNA was also seen in the granules cells and seminiferous tubules of pubertal gonads. Northern analysis revealed that the MIS type II receptor messenger RNA is highly expressed in embryonic, pubertal, and adult testes and ovaries, as well as in the gravid uterus. The timing of expression in the gonads of both sexes was also analyzed by Northern analyses that showed high levels of expression at the time of Müllerian duct regression, much lower levels neonatally and prepubertally and then increased expression again with sexual maturation. The tissue and developmental specificity of expression of this receptor, which make it likely that this is the functional MIS type II receptor, can be used to advantage in therapeutic targeting strategies and to decipher the function of MIS in the gonads.

Endometrial cancer is a receptor-mediated target for Mullerian Inhibiting Substance

“…The MISRII, a transmembrane serine-threonine kinase, controls ligand-binding specificity. The gene for this receptor contains 11 exons and encodes a 63-kDa protein (11,12,13). MIS-bound MISRII phosphorylates the type I receptor, which is responsible for signal transduction; potential candidates for this receptor include ALK3 (14), ALK2 (15,16), and ALK6 (17).…”

Focal Müllerian duct retention in male mice with constitutively activated β-catenin expression in the Müllerian duct mesenchyme

“…At the end of the experiments, the urogenital ridges were fixed overnight in 4% paraformaldehyde at 4°C and used to perform whole mount in situ hybridization as described elsewhere (29,45). Briefly, Amhr2 (46) and Wnt7a (10) riboprobes were prepared using a MaxiScript kit from Ambion with digoxigenin and detected with antidigoxigenin F(ab) 2 fragments and BM purple (all from Roche). Wnt7a staining was considered evidence of retained MD epithelium and scored as either partial or complete if the length of MD epithelium was equal to or greater than the length of the gonad.…”

Synergistic Cooperation between the β-Catenin Signaling Pathway and Steroidogenic Factor 1 in the Activation of the Mullerian Inhibiting Substance Type II Receptor

“…Sertoli cells secrete a transforming growth factor-␤ superfamily member, mullerian inhibiting substance (MIS), 1 also known as anti-mullerian hormone. Its type II receptor, MIS type II receptor (MISRII), also known as anti-mullerian hormone receptor, is expressed in the mesenchymal cells surrounding the mullerian ducts during the regression and in Sertoli cells in testes and granulosa cells in ovaries (2)(3)(4). The MIS type I receptor has not been identified; however, bone morphogenic protein 1a is a strong candidate to be this receptor (5).…”