GROWTH-HORMONE AND PROLACTIN REGULATE THE EXPRESSION OF NERVE GROWTH-FACTOR RECEPTORS IN INS-1 CELLS

We have previously demonstrated that beta-cells express both p75(NGF-R ) and Trk-A, the low and high affinity nerve growth factor (NGF) recep tors, respectively. In the current study, we provide evidences that in the beta-cell line INS-1, the expression of these receptors is tightl y controlled by GH and PRL, two hormones implicated in beta-cell devel opment and function. Within 24 h of treatment of INS-1 cells with huma n (h) GH, the numbers of low and high affinity NGF-binding sites, calc ulated after Scatchard analysis, increase 3- and 2.5-fold, respectivel y. The increase in the concentration of the high affinity NGF-binding sites is paralleled by an increase in Trk-A protein without any change at the mRNA steady state level, suggesting a translational/posttransl ational effect. On the other hand, the increase in low affinity bindin g sites is paralleled by an increase in the p75(NGF-R) mRNA steady sta te level. The effect requires at least 8 h of treatment, and a dose of 50 ng/ml hGH is sufficient to induce an increase in the p75(NGF-R) mR NA steady state level. The effect of hGH can be mimicked in the same t ime- and dose-dependent manner by rat PRL and bovine GH, suggesting th at the expression of NGF receptors can be transduced by both the somat ogenic and lactogenic pathways. Finally, the increase in the p75(NGF-R ) mRNA steady state level after PRL treatment is not due to mRNA stabi lization, suggesting a transcriptional control, and requires concurren t protein synthesis. GH and PRL could thus be important regulators of the sensitivity of beta-cells to NGF.