SOMATOSTATIN REGULATES SOMATOSTATIN RECEPTOR SUBTYPE MESSENGER-RNA EXPRESSION IN GH(3) CELLS

Homologous up-regulation of somatostatin receptors (SSTR) was investigated in the GH(3) clonal pituitary cell line. We report that chronic exposure to SRIF which has high affinity for all SSTR subtypes leads to a net increase in receptor binding and SSTR subtype mRNA. Treatment of cells with 1 mu M SRIF increased specific [I-125-Tyr(11)] SRIF binding to 280% of control values by 24 hr and to 350% by 48hr. Associated with the increase in SSTR binding was a net increase in SSTR subtype mRNA expression. Levels of SSTR1 increased to over 400% of control values by 6 hr and remaied elevated for up to 48 hr. SSTR3, SSTR4, and SSTR5 mRNA was also dramatically increased at 24 and 48 hr. SSTR2 mRNA, in contrast, showed a biphasic response, initially increasingly to 150% of control at 2 hr then decreasing to 50% at 6 hr with normalization by 48 hr. Our data suggests that multiple mechanisms contribute to the highly regulated expression of SSTR subtypes. The identification of specific molecular and cellular mechanisms mediating homologous SSTR up-regulation in GH(3) cells and the involvement this process has in mediating the diverse biological effects of somatostatin are topics of current research. (C) 1994 Academic Press, Inc.