Progesterone and glucocorticoid receptor activation in meningiomas.
The possibility that the female sex steroid progesterone plays a role in meningioma proliferation has been suggested by a number of investigators, and it has been shown that many meningiomas have high-affinity progesterone binding sites. There has been a long-standing debate in the literature as to whether the progesterone receptors that are present in meningiomas are functional. We recently showed, by the use of immunohistochemistry, that the progesterone receptor in meningiomas is localized to the nucleus, suggesting that the receptor is in a location to be activated. In this study, eight meningioma cell cultures were transiently transfected with a construct that contains two palindromic progesterone/glucocorticoid response elements in front of the thymidine kinase promoter and the chloramphenicol acetyl sequence of the tyrosine aminotransferase gene. In all meningioma cell cultures, an increase in the transcription of the progesterone response element construct was observed in the presence of dexamethasone, suggesting that the glucocorticoid receptor in meningiomas is functional. An increase in transcription was observed with the addition of promegestone (R5020), a progesterone agonist, only in meningioma cell cultures that were expressing the progesterone receptor. These data show that both the progesterone and the glucocorticoid receptor in meningiomas are functional and support the concept that progestins and glucocorticoids may play an important role in meningioma growth.
Carroll
R S
RS
Neurosurgical Laboratories, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Zhang
J
J
Dashner
K
K
Black
P M
PM
D000328:Adult; D000368:Aged; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D045167:Progesterone Congeners / Q000494:pharmacology; D011397:Promegestone / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000096:biosynthesis / Q000378:metabolism*; D013937:Thymidine Kinase / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D014444:Tyrosine Transaminase / Q000235:genetics
D045167:Progesterone Congeners; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D011397:Promegestone; D015500:Chloramphenicol O-Acetyltransferase; D014444:Tyrosine Transaminase; D013937:Thymidine Kinase