Molecular Human Reproduction, Vol. 9, No. 10, 611-623,
October 2003
© 2003 European Society of Human Reproduction and Embryology
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Promyelocytic leukaemia zinc finger protein (PLZF) is a glucocorticoid- and progesterone-induced transcription factor in human endometrial stromal cells and myometrial smooth muscle cells
Submitted on May 9, 2003; accepted on June 20, 2003
1 IHF Institute for Hormone and Fertility Research, University of Hamburg, 20251 Hamburg, 2 Institute of Pathology, Department of Gynaecopathology, University Hospital of Hamburg, 20246 Hamburg, Germany 3 Present address: ALLERGOPHARMA, Joachim Ganzer KG, 21465 Reinbek, Germany 4 Present address: Endokrinologikum Hamburg, 20251 Hamburg, Germany
5 To whom correspondence should be addressed at: Endokrinologikum Hamburg, Falkenried 88, 20251 Hamburg, Germany. e-mail: gellersen{at}endokrinologikum.com
The promyelocytic leukaemia zinc finger (PLZF) protein belongs to the family of Krüppel-like zinc finger proteins. It is a transcriptional repressor involved in cell cycle control and has been implicated in limb development, differentiation of myeloid cells, and spermatogenesis. Little is known about the regulation of PLZF expression. In search for mediators of progesterone signalling in the female reproductive tract, we discovered induction of PLZF mRNA in primary cultures of human endometrial stromal cells and myometrial smooth muscle cells (SMC) in response to progesterone. Surprisingly, dexamethasone was a more potent inducer of PLZF expression than progesterone and elicited a sustained up-regulation of PLZF mRNA levels within 2 h. Immunofluorescence showed localization of PLZF to the nuclei of dexamethasone-treated SMC. In uterine biopsies, nuclear staining for PLZF was found in myometrial cells and endometrial stromal cells of the secretory phase. The transcriptional start site of the PLZF gene was located to position –5801 in SMC. Transfected promoter constructs containing up to 4.1 kb of 5'-flanking DNA were not induced by activated glucocorticoid or progesterone receptor. In contrast, co-transfection of c-jun and c-fos expression vectors resulted in stimulation of reporter gene activity, indicating an involvement of AP-1 transcription factors in PLZF expression.
Key words: endometrium/glucocorticoid/myometrium/PLZF/progesterone
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