The effects of the antiprogestin mifepristone, in vivo, and progesterone in vitro on prolactin production by the human decidua in early pregnancy

Abstract

This study investigated the regulatory effect of progesterone on decidual prolactin (dPRL) production during early human pregnancy (6-7 weeks). Patients (n = 7) were treated with the antiprogestin-mifepristone (RU 486; 600 mg single oral dose) for 24-36 h before termination of pregnancy by curettage. Tissue was also obtained from patients without pretreatment in vivo (n = 8) and acted as controls. Decidual tissue was incubated in vitro with and without progesterone and mifepristone for 5 days and the medium changed daily. Prolactin production by decidua parietalis decreased over the period of incubation and was unaffected by addition of progesterone or mifepristone. However, in the group pretreated in vivo with mifepristone, the production of dPRL was markedly lower than in the control group. In contrast, the production of dPRL by decidua capsularis to which trophoblast was attached, was maintained at a constant level over 5 days of culture and was unaffected by pretreatment with mifepristone in vivo or its addition in vitro, or by progesterone. Prolactin was immunolocalized using avidin-biotin immunoperoxidase staining to decidualized cells within the decidua and the intensity of staining was reduced or absent in the decidua parietalis from the mifepristone group compared to controls, but was similar in decidua capsularis in both control and mifepristone groups, in good agreement with the in-vitro production of dPRL. Our findings suggest that the effect of progesterone may be only facilitative, maintaining decidual differentiation, and dPRL production might only be associated with the presence of progesterone-dependent differentiated decidual cells. Apart from progesterone, factors from trophoblast cells can maintain dPRL production during pregnancy.