GH3 CELLS EXPRESSING CONSTITUTIVELY ACTIVE GS-ALPHA (Q227L) SHOW ENHANCED HORMONE-SECRETION AND PROLIFERATION

cAMP levels in GH3gsp cells (Q227L mutation of Gs alpha), in compariso n with uninfected GH3 and GH3vt (with vector alone) cells, were two to three fold (P < 0.01) higher (basal), and 10-20 fold (P<0.001) higher (in the presence of isobutyl methylxanthine, (IBMX)). Proliferation o f GH3gsp cells after 7 days in culture, as determined by cell number a nd [H-3]thymidine incorporation, were up to 25% (respectively P < 0.00 1 and P < 0.02) higher. After chronic (4 days) but not acute (15 min) exposure to forskolin (10 mu M) or dibutyryl cAMP (50 mu M) all cell t ypes showed a greater than 200% (P < 0.001) increase in [H-3]thymidine incorporation. Secretion of prolactin and growth hormone by GH3gsp ce lls were two to four fold (P < 0.001) higher than GH3 and GH3vt cells after 4 h and 10-12 fold (P < 0.001) higher after 8 h. In conclusion G H3 cells possessing Q227L have a higher proliferation rate and secrete higher levels of prolactin and growth hormone which are associated wi th higher levels of cAMP. (C) 1997 Elsevier Science Ireland Ltd.