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RESEARCH |
Obstetrics and Gynaecology, Department of Reproductive and Developmental Sciences, The Queen's Medical Research Institute, Centre for Reproductive Biology, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, Scotland, UK
Correspondence should be addressed to S van den Driesche; Email: svddries{at}staffmail.ed.ac.uk
The molecular mechanisms underlying the control of corpus luteum lifespan in women are not fully understood. Oestradiol has various luteolytic, or luteotrophic, functions in some species, and as it is synthesised within the human corpus luteum, it is an excellent candidate molecule to be a paracrine regulator of luteal function. This study aimed to comprehensively investigate the expression, regulation and effects of oestrogen receptors (ER) in human luteal cells. Genomic oestrogen receptors ER
, ERβ1 and ERβ2 were immunolocalised in human corpora lutea from throughout the luteal phase. mRNA expression was investigated throughout the luteal phase and after luteal rescue with exogenous human chorionic gonadotrophin (hCG). The regulation of ER expression and oestradiol action was investigated in cultures of luteinised granulosa cells. ER subtypes ERβ1 and ERβ2 were localised throughout the luteal phase to steroidogenic cells in the human corpus luteum and cells of the surrounding stroma. Unlike follicular granulosa cells, steroidogenic cells in the corpus luteum showed minimal ER
immunostaining. The presence of endothelial cells in the granulosa cell layer with ERβ1 and ERβ2 positive nuclei was noted. ERβ1 and ERβ2 were differentially regulated across the luteal phase with ERβ1 maximally expressed in the mid-luteal phase, while ERβ2 expression was maximal in the early luteal phase. In vivo and in vitro, hCG had no long-term effect on ER expression, although in vitro hCG and oestradiol acutely down-regulated ERs. Treatment with oestradiol in vitro down-regulated 11β-hydroxysteroid dehydrogenase type 1 and inhibin βA subunit confirming a functional oestradiol response. These data highlight functional and differentially regulated oestradiol reception in human luteal cells.
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