On the Hypothalamic Mechanism by Which Prostaglandin E2 Stimulates Growth Hormone Release

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Abstract
It appears that prostaglandin E2 (PGE2) stimulates pituitary GH release by acting both on hypothalamic and pituitary sites. To determine if the hypothalamic components are at least in part mediated by an inhibition of somatostatin secretion, several experiments were conducted. In vivo treatment of male rats with indomethacin (Id, 2.5 mg/ 100 g BW, single s.c. injection 24 h before) or in vitro administration of the drug (100 μM) to suppress prostaglandin (PG) synthesis, induced a transient increase in basal in vitro release of somatostatin by median eminence (ME) fragments and did not alter that of medial basal hypothalamic (MBH) fragments. Incubation of ME or MBH fragments from males with different concentrations of PGE2 (0.0028–2.8 μM) or PGF2α (0.028–2.8 μM) did not affect basal somatostatin release. PGE2 (0.0028–0.28 μM) also failed to alter the basal release of somatostatin by ME fragments from ovariectomized or ovariectomized, estrogen, progesterone-treated rats. Nevertheless, PGE2 inhibited the stimulatory effect of dopamine (DA) on somatostatin release by ME of male rats. In vitro suppression of PG synthesis with Id failed to facilitate significantly the stimulatory effect of DA on somatostatin release by either ME or MBH fragments, a facilitatory action that would be expected in view of the inhibitory effect of PGE2 on DA-induced somatostatin release. However, if ME fragments from male rats were incubated with PGE2 (0.28 μM) after the in vitro blockade of PG synthesis with Id, an inhibitory effect of the PG on the basal release of somatostatin became apparent, suggesting that incubation of the ME tissue with Id may have resulted in removal of an inhibitory influence exerted by PGE2 and a possible facilititatory effect on somatostatin release exerted by some other factor. Third ventricular injection of PGE2 to intact, conscious, free-moving male rats significantly elevated plasma GH levels 15 min later. A prior i.v. injection of an antisomatostatin serum elevated basal GH levels and produced a remarkable enhancement of the GH release in response to PGE2 indicating that the increase in GH induced by PGE2 was not dependent upon an inhibition of somatostatin release. It is suggested that the effect that PGE2 exerts on the hypothalamus to evoke GH release is primarily mediated by an enhanced secretion of a GH-releasing factor(s). Although PGE2 may play a role in modulating somatostatin release such a role appears to be of only minor importance.