Somatostatin is a tetradecapeptide which was isolated whilst seeking the hypothetical gro wth hormone releasing hormone (GH-RH) in the crude extract of ovine hypoth alami. Since the isolation of somatostatin, the understanding of neural regulation of growth hormone secretion has been greatly facilitated.<BR>Somatostatin in the pituitary stalk median eminence region (SME) is mainly located in axons or nerve terminals (synaptosomes) originating in other regions of the brain; preoptic region. The release of immunoreactive somatostatin from the isolated synaptosomes of hypothala-mic origin was stimulated by high (K⁺) and dopamine. The former effect was completely abolished by the removal of Ca⁺⁺from the media. Immunohistochemical observations revealed the existence of somatostatin and dopamine nerve terminals in a close proximity to the portal vessels of SME. These findings suggest that transsynaptic influence of dopamine on the release of somatostatin into the portal vessels.<BR>When plasma GH levels were observed in intact rats provided with chronic indwelling right atrial cannulae under undisturbed conditions, they showed episodic secretory surge occurring at 3-4 h. The administration of specific anti-serum to somatostatin (A-SS) which acts to neutralize endogenous somatostatin led to elevations of both peak and trough GH levels. The result suggests that somatostatin exerts inhibitory influence on GH secretion and also, episodic GH secretion is mediated by a factor other than somatostatin. The latter presumably represents the action of still uncharacterized GH-RH. Episodic GH secretions were observed in rats performed either anterior or complete hypothalamic deafferentation. Thus, the neural mechanism responsible for generation of episodic GH secretion resides within the medial basal hypothalamus (MBH).<BR>Various brain monoamines have been recognized to modulate GH secretion.These agents are considered to act through the central nervous system which ultimately modulate either somatostatin or GH-RH release. The administration of chlorpromazine (CPZ), an antagonist of brain, monoamines, inhibited episodic GH secretion acting through MBH via a factor other than somatostatin. The findings suggest that brain monoamines play important roles in the generation of episodic GH secretion.<BR>A-SS induced elevations of plasma GH levels requires MBH, particularly hypothalamic ventromedial-arcuate nuclei complex. Since this complex does not send somatostatin to SME, elevations of plasma GH levels after A-SS injection appear to reflect the activity of GH-RH. Preliminary results suggest that dopaminergic mechanism was involved in A-SS induced plasma GH elevation. In addition, somatostatin plays a role in autoregulation of GH secretion.<BR>In summary, A-SS offers a useful tool to investigate the role of somatostatin in the regulation of GH secretion. It is now clear that somatostatin is unlikely to be the sole regulator of GH.