MODULATION OF G-PROTEINS AND 2ND MESSENGER RESPONSIVENESS BY STEROID-HORMONES IN GH3 RAT PITUITARY-TUMOR CELLS

We have investigated the modulation of different G protein alpha- and beta-subunit levels in prolactin (PRL) and growth hormone producing rat pituitary adenoma cells (GH3 cells) in culture after prolonged exposure (6-48 h) to the steroid hormones 17beta-oestradiol and dexamethasone. G(i-3)alpha- and Gbeta-subunits were the only G protein subunits which increased in response to 10(-6) M oestradiol (to approximately 150 and 200% of controls, respectively), while the other alpha-subunits investigated (G(s)alpha, G(i-2)alpha and G(o)alpha) remained relatively unchanged. Thyroliberin (TRH)-and guanosine 5'-[betagamma-imido]trisphosphate (Gpp(NH)p)-elicited adenylyl cyclase (AC) activities were reduced during 6-12 h of oestradiol treatment (by 60 and 20%, respectively), while the inhibitory effect of somatostatin (SRIF) increased by approximately 100%. Dexamethasone (10(-6) m) increased levels of the stimulatory G protein G(s)alpha (to approximately 340%) and decreased levels of G(i-3)alpha (to 25%). After 48 h, the AC response to TRH was reduced by approximately 70%, whereas the effect of the other modulators remained close to controls. We conclude that G protein subunits in GH3 cells are subject to specific regulation by steroid hormones and that this may be important in the tuning of the responsiveness of PRL secretion to hormones in the in vivo situation.