PRESENCE OF A PRE‐SEQUENCE (SIGNAL SEQUENCE) IN THE COMMON PRECURSOR TO ACTH AND ENDORPHIN AND THE ROLE OF GLYCOSYLATION IN PROCESSING OF THE PRECURSOR AND SECRETION OF ACTH AND ENDORPHIN *

Adrenocorticotropin, /3-endorphin, and aand /3-melanocyte-stimulating hormones are peptides with markedly different biological activities yet they are synthesized from a common precursor protein in mouse pituitary tumor cells'-' and in the anterior and intermediate lobes of the Although the two lobes start with similar forms of the precursor, they process these forms to different end produ c t ~ . ~ The release of these hormones is also regulated differently in the two lobes of the pituitary. In order to understand how the levels of these hormones are regulated in the blood, it is necessary to understand how their production is regulated in each lobe of the pituitary. To accomplish this, we have used the AtT-U)/D,,. mouse pituitary tumor cell line as a model system for studying the mechanisms of expression of the gene for the common precursor in the pituitary because this cell line closely mimics the behavior of anterior pituitary cells in culture6.' and is very favorable material for biochemical studies. We have attempted to define the steps involved in synthesis and post-translational processing of the precursor protein in AtT-U) cells and then apply this knowledge to similar studies with monolayer cultures of anterior and intermediate lobe cells of mouse and rat pituitary. In this paper we will describe some of the studies we have done on the early events in processing of the precursor in AtT-20 culture systems and briefly summarize results obtained with cultures of normal pituitary cells.?