Expression and regulation of the pituitary- and placenta-specific human glycoprotein hormone alpha-subunit gene is restricted to the pituitary in transgenic mice.

Abstract

Expression of the glycoprotein hormone alpha subunit occurs in both the pituitary and placenta in humans. However, this study found that expression of this subunit is restricted to the pituitary in mice. An interspecies analysis of human alpha-subunit gene regulation was undertaken, using the transgenic-mouse approach. In mice transgenic for a genomic clone containing the complete human alpha-subunit gene and several kilobases of 5'- and 3'-flanking sequences, cell-type-specific expression and hormonal regulation of the human alpha-subunit transgene occurred in the mouse pituitary, whereas no expression of the transgene was detectable in the mouse placenta. These findings provide strong evidence that a common trans-acting factor(s) regulates glycoprotein hormone alpha-subunit gene expression in the human and mouse pituitaries; however, this factor(s) or a unique factor(s), though functional in the human placenta, is either nonfunctional or absent in the mouse placenta.

Placental-specific expression from the mouse placental lactogen II gene promoter.

“…Expression of a human glycoprotein hormone a-subunit transgene in placental trophoblasts of transgenic mice has been reported by some (27), but not all (28), investigators. Unlike the mPL-II gene, the endogenous mouse a-subunit gene is expressed specifically in the pituitary, and the human transgene is also expressed in the pituitary (27,28). Furthermore, the placental cell type in which the transgene is expressed has not been identified.…”

Activation of the glycoprotein hormone alpha-subunit promoter by a LIM-homeodomain transcription factor.

“…The mechanisms mediating the tissue-specific expression of the a-subunit gene have been the focus of a large number of studies. While a number of DNA elements which are important for at-subunit expression in the placenta have been identified (3,4,11,12,25,28,34,46) amounts of the 5' flanking sequence from the a.-subunit gene can be targeted to the pituitary (4,15). Transgenic animal studies have also provided evidence that different DNA elements are required for expression of the a-subunit in thyrotropes and gonadotropes of the pituitary (20,27).…”

Tissue-specific gene expression in the pituitary: the glycoprotein hormone alpha-subunit gene is regulated by a gonadotrope-specific protein.

“…The human gene shows expression after transfection into primary pituitary cells (6), but these studies are quite difficult and employ a heterogeneous population of cells. In transgenic mice, an 18-kb DNA fragment carrying the entire human a-subunit gene has been demonstrated to direct tissue-specific expression to the pituitary (14), as did a 1.5-kb fragment of the 5'-flanking region of the a-subunit gene (3). We have also demonstrated that 1.8 kb of the 5'-flanking region from this gene can direct pituitary-specific expression of the simian virus 40 T-antigen oncogene (Tag) in transgenic mice (55).…”