Release of Growth Hormone from Purified Somatotrophs: Role of Adenosine 3′,5′-Monophosphate and Guanosine 3′,5′-Monophosphate*

Abstract

Studies were carried out to simultaneously measure cAMP and cGMP accumulation and GH release from acutely dispersed purified somatotrophs obtained from rat adenohypophyses. cAMP accumulation was dramatically increased by both prostaglandin E2 (10(-6) M) and 3-isobutyl-1-methylxanthine (a phosphodiesterase inhibitor, 0.5 mM) within 1 min of their addition, while there was a delay of 8--16 min before a significant increase in GH release was seen. SRIF (100, 10, or 1 ng/ml) completely blocked the stimulated release of GH. SRIF also consistently decreased the elevation of cAMP induced by the two secretagogues, but this decrease was small and not always significant. cGMP was unmeasurable (less than 0.02 fmol/1000 cells) in all of our experiments, while basal cAMP levels were about 1 fmol/1000 cells. We conclude that cAMP plays a role in the intracellular mechanisms governing GH release and that SRIF primarily acts subsequent to cAMP elevation, with a possible secondard or minor action on cAMP formation.

Two types of voltage‐dependent calcium current in rat somatotrophs are reduced by somatostatin.

“…However, the post-receptor events in this cell type are only partially understood so far. Somatostatin has, to a certain extent, an inhibitory CALCIUM CURRENTS AND SOMATOSTATIN4 action on cyclic AMP production (Sheppard, Spence & Kraicer, 1979), but additional mechanisms, such as Ca2+ mobilization, have also been reported (Dorflinger & Schonbrunn, 1983;Sheppard, Moore & Kraicer, 1985;Epelbaum, Enjalbert, Krantic, Musset, Bertrand, Rasolonjanahary, Shu & Kordon, 1987). We have previously shown that somatostatin increased membrane potassium conductance, leading to the hyperpolarization of the membrane potential.…”

Somatostatin Inhibits Basal and Vasoactive Intestinal Peptide-Stimulated Hormone Release by Different Mechanisms in GH Pituitary Cells*

“…It has been suggested that cells which are not responsive to SRIF contribute significantly to the basal cAMP level in these preparations, so that small changes in the cAMP concentration in a specific subpopulation of responsive cells cannot be detected (11,12). However, in a preparation of dispersed rat pituitary cells consisting largely of (>90%) somatotrophs, Sheppard et al (19) did not detect any inhibition of basal cAMP concentrations by SRIF. Similarly, in the clonal GH 4 Ci cell line, the lack of effect of SRIF on basal cAMP accumulation cannot be explained by a masking effect of high background cAMP levels contributed by nontarget cell types.…”

“…There are conflicting reports regarding the effects of SRIF on 1552 DORFLINGER AND SCHONBRUNN Endo • 1983 Volll3«No5 cAMP levels in the anterior pituitary (3,12,(15)(16)(17)(18)(19)(20). Furthermore, SRIF inhibits stimulation of GH secretion by cAMP analogs (21)(22)(23)(24) and phosphodiesterase inhibitors (16,(19)(20)(21)24).…”

Binding and biological actions of prostaglandin E2 and I2 in cells isolated from rabbit gastric mucosa.

“…At the end of the incubation, the cells were flash frozen in methanol-dry ice and stored at -80 'C for cyclic nucleotide determination. Cyclic AMP was extracted and assayed as previously described (Sheppard, Spence & Kraicer, 1979 Fig. 2.…”