Regulation of Chorionic Gonadotropin Gene Expression*

CHORIONIC gonadotropin (CG) is a placental hormone that maintains the corpus luteum of pregnancy. Because CG is expressed at high levels soon after fertilization and implantation, it is used to detect pregnancy at early stages and to monitor the progress of pregnancy during the first trimester (1). CG is also produced in trophoblastic disease and in a variety of different malignancies, and it is useful as a tumor marker in these conditions (2). The mechanisms that control CG production have been investigated extensively, and there are several recent comprehensive reviews (3, 4). CG is a heterodimer composed of α- and β-subunits (Fig. 1). The α-subunit is identical to that in other members of the glycoprotein hormone family (TSH, FSH, LH), whereas the β-subunits in each of the hormones are distinct and confer receptor and biological specificity (5). Little hormone is stored intracellularly and, for the most part, hormone secretion reflects de novo biosynthesis. Therefore, many recent studies have focused on the transcriptional control of CG biosynthesis. The complementary DNAs encoding the α- and β- subunits of CG were among the first hormone sequences to be cloned (2, 6, 7), reflecting, in part, their abundance in the placenta. The α and β genes (8–10) were isolated soon after the cDNAs. The availability of several different CG producing cell lines (3, 4) has allowed relatively rapid progress in the identification of regulatory DNA elements and transcription factors that control CG α- and β-gene transcription. The purpose of this review is to summarize and evaluate recent studies on the structures and transcriptional control of the CG α- and β-genes. Because cAMP is believed to play a central role in the regulation of CG gene transcription, much of the available data concern mechanisms for transcriptional control by the protein kinase A pathway. Information derived from studies of the CG model system may also enhance our understanding of other cAMP-regulated genes.