Autocrine/paracrine roles of extrapituitary growth hormone and prolactin in health and disease: An overview.

Growth hormone (GH) and prolactin (PRL) are both endocrines that are synthesized and released from the pituitary gland into systemic circulation. Both are therefore hormones and both have numerous physiological roles mediated through a myriad of target sites and both have pathophysiological consequences when present in excess or deficiency. GH or PRL gene expression is not, however, confined to the anterior pituitary gland and it occurs widely in many of their central and peripheral sites of action. This may reflect "leaky gene" phenomena and the fact that all cells have the potential to express every gene that is present in their genome. However, the presence of GH or PRL receptors in these extrapituitary sites of GH and PRL production suggests that they are autocrine or paracrine sites of GH and PRL action. These local actions often occur prior to the ontogeny of pituitary somatotrophs and lactotrophs and they may complement or differ from the roles of their pituitary counterparts. Many of these local actions are also of physiological significance, since they are impaired by a blockade of local GH or PRL production or by an antagonism of local GH or PRL action. These local actions may also be of pathophysiological significance, since autocrine or paracrine actions of GH and PRL are thought to be causally involved in a number of disease states, particularly in cancer. Autocrine GH for instance, is thought to be more oncogenic than pituitary GH and selective targeting of the autocrine moiety may provide a therapeutic approach to prevent tumor progression. In summary, GH and PRL are not just endocrine hormones, as they have autocrine and/or paracrine roles in health and disease.