Melanotrope cells as a model to understand the (patho)physiological regulation of hormone secretion

Regulation of hormone secretion is a complex process that comprises the sequential participation of numerous subcellular mechanisms. Hormone secretion is dictated by extracellular stimuli that are transduced intracellularly into activation/deactivation of different mechanisms, such as hormone expression, processing and exocytosis, which will ultimately determine the precise availability of hormone to be secreted. Malfunction in any of these steps may result in deficient or excessive hormone release and the subsequent appearance of endocrine disorders. Given the complexity of this system, it is difficult to find appropriate cellular models wherein to investigate the multiple components of the secretory process in a physiologically relevant, experimentally manipulable setting. In this review, we present recent evidence on the use of the intermediate lobe (IL) of the pituitary as a powerful tool to understand different aspects of the regulated secretory pathway. IL is composed of a single endocrine cell type, alpha-melanocyte stimulating hormone (alpha-MSH)-producing melanotropes, a fact that greatly facilitates its study. Furthermore, melanotropes can be separated using classic cell separation techniques into two cell subtypes showing opposite morphophysiological phenotypes of hypo- and hypersecretory cells. Comparison of their gene expression fingerprints has unveiled the existence of certain genes preferentially expressed in each melanotrope subtype. Because of their direct participation in the secretory pathway, we postulate that characterization of these gene products in an endocrine cell type may represent novel and useful markers for reliably determining the general secretory status in an endocrine gland, as well as a valuable new tool to further investigate this complex process.