Human growth hormone-stimulated mitogenesis of Nb2 node lymphoma cells is not mediated by an immediate acceleration of phosphoinositide metabolism

Lactogenic hormones stimulate the mitogenesis of Nb2-11C rat lymphoma cells and this stimulation is enhanced by 12-O-tetradecanoyl phorbol ester (TPA). The effect of human growth hormone (hGH) and TPA on phosphoinositide metabolism in Nb2-11C cells was tested by measuring the incorporation of [³H] myo-inositol or ³²P or measuring the breakdown of polyphosphoinositides in cells prelabeled with [³H] myo-inositol, ³²P or [³H]arachidonic acid. We found that none of these processes is immediately stimulated by either hGH and/or TPA. Our results indicate that the overall phosphoinositide turnover is slow or confined to small fractions only. On the other hand, the phosphorylation-dephosphorylation cycle of polyphosphoinositides is quite fast and remarkably exceeds the rate of incorporation of [³H]wyo-inositol. Our present results indicate, therefore, that the mitogenic effect of hGH and its enhancement by TPA is not mediated by an immediate increase in phosphoinositide metabolism.