title: Nuclear receptor, coregulator signaling, and chromatin remodeling pathways suggest involvement of the epigenome in the steroid hormone response of endometrium and abnormalities in endometriosis.
abstract: Human endometrium, a steroid hormone-dependent tissue, displays complex cellular regulation mediated by nuclear receptors (NRs). The NRs interact with histone-modifying and DNA-methylating/-demethylating enzymes in the transcriptional complex. We investigated NRs, their coregulators, and associated signaling pathways in endometrium across the normal menstrual cycle and in endometriosis, an estrogen-dependent, progesterone-resistant disorder. Endometrial tissue was processed for analysis of 84 genes using NR and coregulator polymerase chain reaction (PCR) arrays. Select genes were validated by immunohistochemistry. Ingenuity pathway analysis identified DNA methylation and transcriptional repression signaling as the most affected pathway in endometrium in women with versus without endometriosis, regardless of cycle phase. Thyroid hormone receptor (THR) and vitamin D receptor (VDR) pathways were also regulated in normal and disease endometrium by activation of TH or vitamin D regulated genes. These data support the involvement of the epigenome in steroid hormone response of normal endometrium throughout the cycle and abnormalities in endometrium in women with endometriosis.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94143, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zelenko
authors.forename: L
authors.initials: L
authors.lastname: Aghajanova
authors.forename: J C
authors.initials: JC
authors.lastname: Irwin
authors.forename: Linda C
authors.initials: LC
authors.lastname: Giudice
mesh_terms: D000328:Adult; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D004351:Drug Resistance; D004715:Endometriosis / Q000188:drug therapy / Q000378:metabolism*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008597:Menstrual Cycle / Q000378:metabolism*; D008875:Middle Aged; D011372:Progestins / Q000494:pharmacology; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
chemical_list: D004967:Estrogens; D011372:Progestins; D018167:Receptors, Calcitriol; D011988:Receptors, Thyroid Hormone