Expression of Müllerian-Inhibiting Substance/Anti-Müllerian Hormone Type II Receptor in the Human Theca Cells

Context: M ullerian-inhibiting substance/anti-M ullerian hormone (MIS/AMH) is produced in the ovarian granulosa cells, and it is believed to inhibit ovarian folliculogenesis and steroidogenesis in women of reproductive age. Objective: To investigate the expression of MIS/AMH type II receptor (MISRII/AMHRII) that binds MIS/AMH in the ovaries of reproductive-age women; to identify the exact targets of MIS/AMH. Design: Laboratory study using human ovarian tissue. Setting: University hospital. Patients: Tissue samples from 25 patients who had undergone ovarian surgery. Interventions: The segregation of ovarian granulosa and theca cells by laser microdissection was followed by RT-PCR, analyzing MISRII/AMHRII mRNA expression. Afterward, in situ hybridization and immunohistochemistry were performed to determine the localization of MISRII/AMHRII mRNA and protein expression. Main Outcome Measures: MISRII/AMHRII mRNA expression by RT-PCR, in situ hybridization, and immunohistochemistry. Results: MISRII/AMHRII were expressed in granulosa and theca cells of preantral and antral follicles. The granulosa cells showed stronger MISRII/AMHRII expression than theca cells. MISRII/AMHRII mRNA staining of granulosa and theca cells in large antral follicles, early atretic follicles, and corpus luteum waned but were still detected weakly, showing higher expression in theca cells than in granulosa cells. However, MISRII/AMHRII protein in the granulosa layer of the atretic follicle and corpus luteum could not be assessed. Conclusions: As MISRII/AMHRII is expressed in both granulosa and theca cells, this indicates that MIS/ AMH, produced in the granulosa cells, is active in the theca cells as well. MIS/AMH is most likely actively involved not only in the autocrine and endocrine processes but also in the paracrine processes involving theca cells.