CIS-UNSATURATED FREE FATTY-ACIDS BLOCK GROWTH-HORMONE AND PROLACTIN SECRETION IN THYROTROPIN-RELEASING HORMONE-STIMULATED GH(3) CELLS BY PERTURBING THE FUNCTION OF PLASMA-MEMBRANE INTEGRAL PROTEINS

In vivo FFA block basal and stimulated GH secretion and have been impl icated in the pathogenesis of the altered GH secretion present in obes ity and Cushing's syndrome. Although a direct action on the somatotrop h cell has been postulated, the FFA mechanism of action is unknown. Th e main biological target for FFA action is the cellular membrane, and it has been shown that these metabolites can block the activity of a n umber of plasma membrane pumps, channels, and receptor systems. In the present work, it was observed using different types of pituitary cell s (GH(3), GH(1)C(1), and rat pituitary primary cultures) that cis-unsa turated fatty acids, such as oleic, 1) do not perturb TRH binding or t he homologous desensitization of the TRH receptor. 2) inhibit TRH-indu ced inositol 1,4,5-trosphosphate/diacylglycerol generation, probably b y a direct perturbation of phospholipase C; 3), reduce the TRH-induced intracellular Ca2- redistribution and the ensuing changes in membrane potential; 4) completely inhibit the [Ca2+](i), rise due to the TRH-i nduced CA(2+) efflux through plasma membrane Ca2+ pumps. These results suggest that cis-unsaturated FFA such a oleic acid selectively pertur b the function of integral membrane proteins such as enzymes, channels , and pumps without perturbing the binding of ligands to receptors.