FERRITIN HEAVY-CHAIN IS A PROGESTERONE-INDUCIBLE MARKER IN THE UTERUSDURING PREGNANCY

The female sex steroid, progesterone, plays a central role in mammalia n pregnancy by regulating crucial events in the uterus such as transfo rmation of endometrium for implantation and maintenance of pregnancy, The hormone acts through its specific nuclear receptor and modulates t he functions of target cells by controlling the synthesis of specific proteins. The identity of genes that are regulated by progesterone in the uterus during various phases of pregnancy, however, remains largel y unknown. In this study, we employed a differential gene-screening me thod to identify the gene encoding ferritin heavy chain (FHC), a compo nent of the multisubunit iron-binding protein ferritin, as being regul ated by progesterone in the uterus. We observed that uterine expressio n of the FHC messenger RNAs (mRNAs) rose dramatically at the onset of pregnancy, coincident with the surge of progesterone. FHC expression c ontinued at this elevated level throughout gestation when the progeste rone concentration remained high. At term, FHC expression declined sha rply as the progesterone concentration dropped. We localized FHC prote ins exclusively in uterine stromal cells, a major site of action of pr ogesterone during pregnancy. Administration of mifepristone, an antipr ogestin, during the early stages of pregnancy abolished both FHC mRNA and protein expression, clearly suggesting a primary role of progester one in the regulation of this gene. Consistent with this scenario, adm inistration of progesterone to ovariectomized animals after a brief es trogen priming led to a marked (25-fold) induction of FHC mRNA in the uterus, whereas estrogen, dexamethasone, or dihydrotestosterone had no effect. Based on these results, we propose that FHC is a novel and us eful marker to study progesterone-regulated events in the uterus durin g pregnancy.