NOVEL PERSPECTIVES ON PITUITARY AND BRAIN ANGIOTENSINOGEN

All the angiotensin peptides originate from angiotensinogen, a glycopr otein synthesized by several tissues, including the brain and the ante rior pituitary. In the rat, immunohistochemistry has been used to loca lize angiotensinogen in gonadotropes and in uncharacterized cells surr ounding sinusoids. Both cell types are capable of secreting angiotensi ngen in cell culture; only the gonadotropes contain angiotensin II (An gII) and are capable of secreting it in culture. It has been asserted that the perisinusoidal cells are the only source of angiotensinogen f or the generation of AngII by gonadotropes. Our current data favor the existence of a complete intracellular renin-angiotensin system (RAS) in gonadotropes and a separate extracellular system which utilizes the high concentration of angiotensinogen from perisinusoidal cells. Furt hermore, we postulate that gonadotrope AngII serves mainly reproductiv e functions, while the proximity of angiotensinogen-secreting cells to folliculostellate cells, and their access to the intercellular sinuso idal and follicular spaces, places the extracellular RAS in a strategi c position to affect pituitary growth and the mediation of acute-phase immune responses. In the rat brain, angiotensinogen is expressed by t he 16-18th day of fetal life and by areas generally concerned with vas opressor, electrolyte, and fluid homeostasis. Antisense deoxyoligonucl eotides to angiotensinogen mRNA lower blood pressure in hypertensive r ats and inhibit in vitro growth of neuroblastoma cells, indicating a s ignificant role for angiotensinogen in mitogenic and homeostatic funct ions. It is commonly agreed that astrocytes express angiotensinogen. N euronal angiotensinogen has also been demonstrated by immunohistochemi stry, as a secretion from neuronal cell cultures, and by reverse-trans criptase polymerase chain reaction. The fate of secreted astrocytic an d neuronal angiotensinogen remains obscure. Angiotensinogen is regulat ed in a tissue-specific manner with smaller or absent responses observ ed for brain tissue. By using astrocyte and neuronal cultures the acti ons on angiotensinogen production of growth hormone, IGF-1, inflammato ry lipopolysaccharide, and phorbol ester have been examined. Recent ob servations show that angiotensinogen is regulated positively or negati vely by glucocorticoids and that a positive synergism between cAMP and glucocorticoids exists. On the basis of analogous systems for other p roteins, a scheme involving glucocorticoid receptors, CREB, and AP-1 t ranscription factors is formulated to explain glucocorticoid-cAMP inte ractions These transcriptional interactions may form a significant fun ctional Link between the RAS and adrenergic mechanisms. (C) 1997 Acade mic Press.