HOXA10 expression is repressed by progesterone in the myometrium: Differential tissue-specific regulation of HOX gene expression in the reproductive tract

HOX genes are essential regulators of development in all multicellular orga nisms, including humans. We have previously shown that HOXA10 is expressed in the developing uterus and later in the adult human endometrium. HOX gene s regulate endometrial development in response to sex steroids. Here, we de monstrate that HOXA10 is expressed in the myometrium as well. In situ hybri dization reveals abundant HOXA10 expression, and Northern analysis demonstr ates differential HOX gene expression in the myometrium throughout the mens trual cycle. HOXA10 expression decreases in the midsecretory phase, coincid ing with high serum progesterone levels. Treatment of primary myometrial ce ll cultures with progesterone decreases HOXA10 expression in vitro-parallel ing the expression seen in vivo. Despite the presence of progesterone recep tors in the endometrium and myometrium, HOXA10 is differentially regulated in each tissue by progesterone. HOXA10 expression is induced in the stroma and decreased in the myometrium by progesterone. he differential tissue-specific response of this gene in response to proges terone is likely mediated by sex steroid receptor coactivators or corepress ors. Decreased myometrial expression of developmental regulatory genes such as HOXA10 in the nonpregnant uterus may dedifferentiate the myometrium and allow growth in preparation for pregnancy.