Growth and differentiation factors derived from the N-terminal domain of pro-opiomelanocortin

1. We describe a novel paracrine control system in the pituitary gland, consisting of peptides derived from the N-terminal fragment of pro-opiomelanocortin (N-POMC), for example POMC(1-74) and gamma3-melanocyte-stimulating hormone (MSH). 2. By searching the target cells of these N-POMC fragments, using the rise of intracellular free calcium as a response system and single cell reverse transcription-polymerase chain reaction of hormone mRNA as a cell type identification method, we found that a considerable number of cells in normal rat pituitary display combinatorial expression of different pituitary hormone genes (further referred to as 'multihormone mRNA cells'), without indication that all these cells also produce or store the respective hormones translatable from these mRNA. The N-POMC fragments POMC(1-74) and gamma3-MSH preferentially target particular subsets of these multihormone mRNA cells. 3. We discovered a potentially novel receptor for gamma3-MSH on these cells; more precisely, on cells coexpressing growth hormone and prolactin. The putative novel receptor displays properties highly divergent from those of the known gamma3-MSH receptor (i.e. the melanocortin-3 receptor) and even of all other melanocortin receptors cloned today.