Intrahypothalamic Mu-, not Delta- or Kappa-Opioid Receptor Activation Causes Growth Hormone Secretion

Abstract The possible effects of opioid receptor agonists on growth hormone (GH)-releasing factor or somatostatin neurons were examined by measuring the effects of localized intracerebral injections of mu-, delta- and kappa-selective agonists on GH secretion. Serial GH concentrations were measured in plasma in unanaesthetized male rats chronically prepared with venous and intracerebral cannulae, before and after treatment with bilateral intracerebral injections of opioid agonists in the preoptic anterior hypothalamic area and medial basal hypothalamus. In the medial basal hypothalamus, injections of the mu-agonist DAGO (Tyr-D-Ala-Gly-(Me)Phe-Gly-ol) caused dose-responsive increases in GH, the maximally effective dose being 0.001 nmoles. Injection of 10,000-fold higher doses of the delta-agonist DPDPE ([D-Pen, D-Pen]enkephalin) and the kappa-agonist U50,488H were also effective in stimulating GH secretion. In the preoptic anterior hypothalamic area, DAGO caused dose-responsive increases in GH, the maximally effective dose being 0.01 nmoles. U50.488H was ineffective at 1,000-fold higher doses while DPDPE was effective at 100- to 1,000-fold higher doses. We conclude that hypothalamic mu-opioid receptor activation on or near somatostatin or GH-releasing factor neurons causes GH secretion. Opioids capable of acting on other opioid receptors may also stimulate GH secretion, though only at doses that seem likely to affect mu-receptors.