BES2003 Oral Communications Reproduction and Development (8 abstracts)
A functional polymorphism in the extrapituitary prolactin promoter has opposing effects on prolactin gene expression in T-lymphocytes and endometrial stromal cells but is not associated with unexplained recurrent miscarriages
A Stevens 1 , W Brintnell 2 , J Worthington 2 , G Zoumpoulidou 3 , S Jivraj 3 , L Regan 3 , J Brosens 3 & JRE Davis 1
1Endocrine Sciences Research Group, University of Manchester, UK; 2ARC Epidemiology Research Unit, University of Manchester, UK; 3Department of Obstetrics & Gynaecology, Imperial College Faculty of Medicine, St Mary's Hospital, London, UK.
Prolactin is expressed in lymphoid cells and differentiating (decidualised) endometrial stromal cells (ESCs) under the control of an alternative upstream promoter, distinct from the pituitary-specific promoter. Local prolactin action may have immunomodulatory effects. Th1/Th2 imbalance may be an important cause of habitual abortions in man but the mechanism is unknown. Recently, we characterised a G/T SNP at position -1149 that altered prolactin production by lymphocytes, and was associated with systemic lupus erythematosus. We now examined the effects of this SNP on prolactin expression in ESCs and assessed its prevalence in patients with recurrent miscarriages.
Effects on gene expression in Jurkat T cells and primary human ESCs were determined by transiently transfecting a reporter gene construct under the control of either the G or T promoter allele. Cells were then treated with 8-bromo-cAMP or control medium for 24h. Genotyping for the -1149 SNP was performed using 'Snapshot' on an ABI3700 analyser. 100 Caucasian affected women were studied and compared with a panel of healthy UK Caucasoid control subjects (n=394). Unexplained recurrent miscarriage was defined as = 3 consecutive pregnancy losses, normal karyotype of both partners, and absence of an underlying prothrombotic disorder. Transient transfection studies confirmed that the G allele produced higher basal and cAMP-stimulated promoter activity in Jurkat T cells. In primary ESC cultures, however, the basal and induced reporter gene activity under control of the G allele variant was reduced to 50% of that observed with the T allele. The GG, GT, and TT genotype frequency in women with unexplained recurrent miscarriages was 0.40, 0.47, and 0.13, respectively, similar to that of the control subjects.
In summary, the -1149 prolactin promoter SNP has opposing effects upon PRL gene expression in T lymphocytes versus differentiating ESCs, whose mechanism is still unclear, but no association was found with unexplained recurrent miscarriages
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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