Prolactin (PRL) is produced in the pituitary and at extrapituitary sitesd Human thymocytes, T-cells and endometrium produce prolactin. In hese tissues gene transcription is directed from an alternative upsstream promter. PRL is thought to act as a locally produced cytokine with relevance for immune regulation nd T-cell function. We are studying PRL transcriptional regulation in the human lyymphoblastoid cell line is transfected with a fragemnt of the upestream promoter linked to luciferases which acts as areproter. We find that activation of T-cells increases promoter activity as does cAMP. Mutation or deleteion of the cAMP responsive element (CRE) reduces the response to cAMP by onne half. At present we are engaged in defining other transcription factors which bind to the distal PRL promoter and modulate its activity. To this end we have generated mutantions in these factors and examined their effect on the upstream PRL promoter.