Regulation of human chorionic somatomammotropin gene expression in rat pituitary tumour cells

A gene (hCS-1) coding for human chorionic somatomammotropin (hCS) was introduced stably into rat anterior pituitary tumour (GC) cells. These cells were treated with hormones, growth and other factors implicated in hCS production in the placenta. Levels of hCS-1 gene mRNA and hCS release were increased by thyroid hormone, dexamethasone, a cyclic adenosine monophosphate (cAMP) analogue (8-bromo-cAMP), and phorbol ester, phorbol-12-myristate-13-acetate (PMA). No significant response to insulin, medium glucose levels, epidermal growth factor or insulin-like growth factor II was observed. A hybrid gene containing the 5'-flanking sequences from the intact hCS-1 gene was also stably introduced into GC cells. These cells were tested to determine the contribution made by 5'-flanking DNA on the responses observed with the intact gene. Although expression of this hybrid gene was stimulated by thyroid hormone, no response to 8-bromo-cAMP or PMA was observed. These data suggest that sequences downstream of the transcription initiation site might play an important role in hCS gene expression and regulation.