Transcriptional regulation of the human prolactin gene

The human prolactin gene is mainly expressed in the anterior pituitary under the control of the transcription factor Pit-1. Positive and negative regulatory elements have been identified in the 5'-flanking region of the hPRL gene. Binding sites for the cell-specific factor Pit-1 and for ubiquitous factors were identified in a more than 5 000 base pair long upstream region. In addition, prolactin expression is modulated by extracellular factors such as dopamine, thyrotropine releasing hormone, thyroid hormone and steroids. Factors acting through signal transduction pathways (cAMP, Ca2+) regulate hPRL expression mainly via the proximal promoter (-250/+1). Protein-kinases and phosphatases modulate the activation function of transcription factors Pit-1 AP1 and other, binding to their respective sites on the promoter. The estrogen receptor activates hPRL expression by binding to a distal response element, while glucocorticoid and thyroid hormone receptors repress hPRL gene transcription by interfering with the activating function of, respectively, Pit-1 and AP1. in extrapituitary transcription of the hPRL, gene is initiated at an alternative, far upstream, site and hPRL expression is controlled by a lymphocyte-specific element. Binding sites for cell-specific and ubiquitous factors were detected in this region.