GROWTH HORMONE-RELEASING HORMONE STIMULATES CAMP RELEASE IN SUPERFUSED RAT PITUITARY-CELLS

The release of growth hormone (GH) and cAMP was studied in superfused rat pituitary cells by infusing growth hormone-releasing hormone (GHRH ) at different doses or a combination of GHRH and somatostatin 14 (SS- 14). Three-minute pulses of GHRH caused a dose-dependent GH and cAMP r elease (effective concentration of 50% of the maximal biological effec t is 0.21 nM and 52.5 nM, respectively). The lowest effective doses of GHRH in the superfusion system were 0.03 nM for GH release and 0.3 nM for cAMP discharge when 3-min pulses were applied. The amount of cAMP liberated from the cells was not proportional to GH release: cAMP res ponses to low doses of GHRH were disproportionally small and the gradu al increase in the release of cAMP after high doses of GHRH was not fo llowed by a parallel rise in GH release, The desensitization induced b y repeated pulses or prolonged infusion of GHRH resulted in a greater reduction in GH release than in cAMP liberation. A simultaneous infusi on of SS-14 completely blocked GH release stimulated by GHRH blt did n ot inhibit the immediate release of cAMP caused by GHRH. An abrupt dec rease in GHRH-stimulated GH release induced by SS-14 was followed by o nly a minimal reduction in cAMP liberation 9 min later. Our findings i ndicate that a discharge of cAMP is stimulated after a GHRH pulse, but this effect alone cannot maintain the release of GH. Other steps of t he signal transduction mechanisms that are independent of the cAMP rou te may participate in the process of GH release, The nature of the mec hanisms involved in the mediation of GH release may vary with the desk s of GHRH used.