MULTI-RESPONSIVENESS OF SINGLE ANTERIOR-PITUITARY-CELLS TO HYPOTHALAMIC-RELEASING HORMONES - A CELLULAR BASIS FOR PARADOXICAL SECRETION

The classic view for hypothalamic regulation of anterior pituitary IAP ) hormone secretion holds that release of each AP hormone is controlle d specifically by a corresponding hypothalamic-releasing hormone (HRH) . In this scenario, binding of a given HRH (thyrotropin-, growth hormo ne-, corticotropin-, and luteinizing hormone-releasing hormones to spe cific receptors in its target cell increases the concentration of cyto solic Ca2+ ([Ca2+](i)), thereby selectively stimulating the release of the appropriate hormone, However, ''paradoxical'' responses of AP cel ls to the four well-established HRHs have been observed repeatedly wit h both in vivo and in vitro systems, raising the possibility of functi onal overlap between the different AP cell types. To explore this poss ibility, we evaluated the effects of HRHs on [Ca2+](i) in single AF ce lls identified immunocytochemically by the hormone they stored. We fou nd that each of the fire major AP cell types contained discrete subpop ulations that were able to respond to several HRHs. The relative abund ance of these multi-responsive cells was 59% far Iactotropes, 33% for thyrotropes, and in the range of 47-55% for gonadotropes, corticotrope s, and somatotropes. Analysis of prolactin release from single living cells revealed that each of the four HRHs tested were able to induce h ormone release from a discrete lactotrope subpopulation, the size of w hich corresponded closely to that in which [Ca2+](i) changes were indu ced by the same secretagogues. When viewed as a whole, our diverse fun ctional measurements of multi-responsiveness suggest that hypothalamic control of pituitary function is more complicated than previously env isioned. Moreover, they provide a cellular basis for the so-called ''p aradoxical'' behavior of pituitary cells to hypothalamic hypophysiotro pic agents.