Progesterone membrane receptor component 1 expression in the immature rat ovary and its role in mediating progesterone's antiapoptotic action.
Progesterone receptor membrane component-1 (PGRMC1) interacts with plasminogen activator inhibitor RNA binding protein-1 (PAIRBP1), a membrane-associated protein involved in the antiapoptotic action of progesterone (P4). In this paper, the first studies were designed to assess the ovarian expression pattern of PGRMC1 and PAIRBP1. Western blot analysis revealed that spontaneously immortalized granulosa cells (SIGCs) as well as granulosa and luteal cells express both proteins. Luteal cells were shown to express more PGRMC1 than granulosa cells. Immunohistochemical studies confirmed this and demonstrated that PGRMC1 was present in thecal/stromal cells, ovarian surface epithelial cells, and oocytes. PAIRBP1 was also expressed in thecal/stromal cells and ovarian surface epithelial cells but not oocytes. Furthermore, PAIRBP1 and PGRMC1 were detected among the biotinylated surface proteins that were isolated by avidin affinity purification, indicating that they localized to the extracellular surface of the plasma membrane. Confocal microscopy revealed that both of these proteins colocalize to the plasma membrane as well as the cytoplasm. The second studies were designed to assess PGRMC1's role in P4's antiapoptotic actions. These studies showed that overexpression of PGRMC1 increased 3H-P4 binding and P4 responsiveness. Conversely, treatment with a PGRMC1 antibody blocked P4's antiapoptotic action. Taken together, the present findings indicate that both PAIRBP1 and PGRMC1 show a similar expression pattern within the ovary and colocalize to the extracellular surface of the plasma membrane. At the plasma membrane, these two proteins interact to form a complex that is required for P4 to transduce its antiapoptotic action.
Peluso
J J
JJ
Department of Cell Biology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA. peluso@nso2.uchc.edu
Pappalardo
A
A
Losel
Ralf
R
Wehling
Martin
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects; D008565:Membrane Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D010053:Ovary / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D015849:Plasminogen Inactivators / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011980:Receptors, Progesterone / Q000032:analysis* / Q000235:genetics / Q000502:physiology
D006063:Chorionic Gonadotropin; D008565:Membrane Proteins; C486424:Pgrmc1 protein, rat; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011980:Receptors, Progesterone; D011374:Progesterone