RESUMO
Progesterone is a sexual steroid hormone that has a critical role in reproductive processes in males and females of several species, including humans. Furthermore, progesterone has been associated with pathological diseases such as breast, gynecological and brain cancer, regulating cell proliferation, apoptosis, and metastasis. In the past, progesterone actions were thought to be only mediated by its intracellular receptor (PR). However, recent evidence has demonstrated that membrane progesterone receptors (mPRs) mediate most of the non-classical progesterone actions. The role of the different mPRs subtypes in progesterone effects in reproduction and cancer is an emerging and exciting research area. Here we review studies to date regarding mPRs role in reproduction and cancer and discuss their functions and clinical relevance, suggesting mPRs as putative pharmacological targets and disease markers in cancer and diseases associated with reproduction.
Assuntos
Membrana Celular/metabolismo , Neoplasias/metabolismo , Receptores de Progesterona/metabolismo , Reprodução , Animais , Feminino , Humanos , Masculino , Progesterona/metabolismo , Transdução de SinaisRESUMO
Progesterone (P) participates in the regulation of the growth of several tumors, including astrocytomas, the most common and malignant human brain tumors. It has been reported that P induces astrocytomas growth in part by its interaction with its intracellular receptors (PR). Recently, it has been reported that membrane progesterone receptors (mPRs) are expressed in ovarian and breast cancer cells, and that P could exert some actions through these receptors, however, it is unknown whether mPRs are expressed in astrocytomas. In this work, U251 and U87 cell lines derived from human astrocytomas grade IV were used to study the expression, localization and hormonal regulation of three mPRs subtypes. Using RT-qPCR and Western blot techniques, we found that mPRα and mPRß are clearly expressed at mRNA and protein levels in astrocytoma cells whereas mPRγ was barely expressed in these cells. Immunofluorescence staining showed that mPRα and mPRß were mainly located in the cell surface. Flow cytometry assays demonstrated that in U251 and U87 cells, mPRß is expressed by a higher percentage of both permeabilized and non-permeabilized cells as compared with mPRα. The percentage of cells expressing mPRγ was very low. P and estradiol (E) (10, 100 nM and 1 µM) decreased mPRα protein content at 12 h. In contrast, both P (100 nM and 1 µM) and E (10 and 100 nM) increased mPRß content. Finally, by in silico analysis, we identified that mPRα, mPRß and mPRγ promoters contain several progesterone and estrogen response elements. Our results indicate that mPRs are expressed in human astrocytoma cells, exhibiting a differential regulation by E and P. These data suggest that some P actions in astrocytoma cells may be mediated by mPRs.