Effects of combined progesterone and beta-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 in order 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 progesterone 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 down-regulated expression of genes involved in cell communication, signal transduction, channel activity, inflammatory response and differentiation. Up-regulated processes included cell survival, gene transcription, steroid hormone biosynthesis, muscle development, insulin receptor signalling and cell growth.