Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2003) 5 S26

BES2003 Symposia Prolactin: Novel Aspects (4 abstracts)

Role and regulation of decidual PRL expression: Implications for pregnancy failure

J Brosens


Institute of Reproductive and Developmental Biology, Imperial College Faculty of Medicine, London, UK.


In the human endometrium, the postovulatory rise in ovarian progesterone results in the influx of distinct local immune cells and induces the coordinated expression of certain gene sets that initially define a limited period of uterine receptivity and subsequently control differentiation of the stromal compartment (decidualisation). Decidualisation is critical for trophoblast invasion and the formation of a haemochorial placenta. Pathologically, a spectrum of reproductive disorders, including recurrent miscarriages and preeclampsia, are characterised by the presence of aberrant endometrial immune cells, altered local inflammatory responses, and impaired decidualisation. PRL expression, under control of the upstream extrapituitary promoter, is a cardinal marker of decidualisation. Its expression in differentiating human endometrial stromal cells (ESC) is dependent upon elevated intracellular cAMP levels and progesterone. Progesterone exerts its action on target cells through binding and activation of the progesterone receptor (PR), a member of the steroid/thyroid hormone superfamily of transcription factors. However, PR-dependent transactivation of the decidual PRL gene requires the coordinated induction and activation of diverse transcription factors, such as C/EBP beta, STAT5, and members of the forkhead/winged helix family of transcription factors. These nuclear factors are capable of physically interacting with ligand-bound PR, suggesting a role for PR as a platform for the formation of decidua-specific multimeric transcriptional complexes. Th-1/Th-2 imbalance and antiphospholipid antibodies are thought to be important causes of habitual abortions and are associated with preeclampsia. In-vitro studies demonstrated that interferon gamma (IFNgamma), a Th-1 cytokine, and ID2, a monoclonal antiphospholipid antibody, interfere with the formations of PR-dependent transcriptosomes, resulting in impaired decidualisation process.

Volume 5

22nd Joint Meeting of the British Endocrine Societies

British Endocrine Societies 

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