title: Effects of combined progesterone and 17β-estradiol treatment on the transcriptome of cultured human myometrial smooth muscle cells.
abstract: A transcriptomic analysis of cultured human uterine smooth muscle cells (hUtSMCs) was performed to examine gene expression profiles in smooth muscle in an environment containing the two major steroid hormones that regulate the human myometrium in physiological states associated with estrous, pregnancy, labor, and pathophysiological states such as leiomyoma and endometrial cancer. hUtSMCs were treated with progesterone (P4) and 17β-estradiol (E2) individually and in combination, in the presence and absence of RU486 (mifepristone). Transcription of many genes was modulated in the presence of P4 or E2 alone, but almost six times more genes were transcriptionally modulated in the presence of the P4/E2 hormone combination. In total 796 annotated genes were significantly differentially expressed in the presence of both P4 and E2 relative to their expression in untreated cells. Functional withdrawal of P4 by addition of RU486 effectively reversed almost all transcriptional changes caused by P4/E2 treatment. Gene ontology analysis of differentially expressed genes revealed a strong association between P4/E2 treatment and downregulated expression of genes involved in cell communication, signal transduction, channel activity, inflammatory response, and differentiation. Upregulated processes included cell survival, gene transcription, steroid hormone biosynthesis, muscle development, insulin receptor signaling, and cell growth.
authors.affiliation: National Centre for Biomedical Engineering Science, National University of Ireland Galway, Galway, Ireland.
authors.forename: Sreenath
authors.initials: S
authors.lastname: Chandran
authors.affiliation: National Centre for Biomedical Engineering Science, National University of Ireland Galway, Galway, Ireland.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Cairns
authors.affiliation: National Centre for Biomedical Engineering Science, National University of Ireland Galway, Galway, Ireland.
authors.forename: Margaret
authors.initials: M
authors.lastname: O'Brien
authors.affiliation: National Centre for Biomedical Engineering Science, National University of Ireland Galway, Galway, Ireland.
authors.forename: Enda
authors.initials: E
authors.lastname: O'Connell
authors.affiliation: National Centre for Biomedical Engineering Science, National University of Ireland Galway, Galway, Ireland.
authors.forename: Kaveh
authors.initials: K
authors.lastname: Mashayekhi
authors.affiliation: National Centre for Biomedical Engineering Science, National University of Ireland Galway, Galway, Ireland Terry.Smith@nuigalway.ie.
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Smith
mesh_terms: D001665:Binding Sites; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D063990:Gene Ontology; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009215:Myometrium / Q000166:cytology*; D011374:Progesterone / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects* / Q000235:genetics
chemical_list: D014157:Transcription Factors; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol
keywords: 17β-estradiol; microarray; progesterone; transcriptomics; uterine smooth muscle cells