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Somatostatin is released in the blood, in synaptic clefts, and in the intercellular space in response to a variety of stimuli. In view of its multiple functions, various sites of synthesis and release, and rapid inactivation, as well as extremely low levels of somatostatin in the peripheral blood, somatostatin can hardly be considered to be a hormone whose target is reached via the general circulation. The target organs or cells may be located near the somatostatin-producing cells and can be reached via local circulation such as the hypophyseal portal system and the microportal circulation in the gut mucous membrane. Somatostatin released from the neurons acts as a hypophyseotropic hormone and a neurotransmitter or neuromodulator. Furthermore, somatostatin may also act in a paracrine fashion by being released into the intercellular space. This space may sometimes be compartmentalized by tight junctions so that the action of the peptideis limited only to the adjacent cells. In this fashion, the pancreatic islet somatostatin influences nearby A- and B-cell activities. Gut D cells, prototypes of APUD or paraneuron cells, show considerable similarity to neurosecretory cells not only in biochemical processes but also morphologically. While the somatostatin neurons in the brain respond to dopaminergic and catecholaminergic agonists, D cells in the gut respond to chemical stimuli in the lumen by sensing them with microvilli. They release somatostatin into the blood stream, into the intercellular space, and into the gastric and intestinal lumen. Luminal somatostatin may affect other endocrine and nonendocrine cells in the mucous membrane of the gut. It is noted that the same stimulatory agent does not always stimulate somatostatin release from different organs; one agent stimulates the release from one organ and suppresses release from the other organ.

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Implants of growth hormone (GH) in the rat median eminence decrease pituitary weight and G H content, suggesting a negative feedback effect of G H at the hypothalamic level (1). Demonstration of the presence of TSH in the hypothalamus also implies that TSH might affect hypothalamic activity (2). Recently Oliver et al.(3) reported that hypophysial portal blood not only flows from median eminence to the pituitary gland but, as well, there is retrograde circulation via the neurohypophysis to the primary capillary plexus. Further, portal plasma contains high concentrations of both neurohypophysial and adenohypophysial hormones. These results favor a view that the pituitary hormones might exert a direct feedback control on the hypophysiotropic hormones of the hypothalamus. On the other hand, thyroidectomy results in the degranulation of the pituitary acidophil cells in rats (4), but also decreases pituitary G H content ( 5 ) , and impairs G H secretion (6). The mechanism by which T, and T3 influence G H synthesis in the pituitary is still unknown, but these thyroid hormones appear to exert a direct effect on the pituitary gland (7).Most anesthetics are known to change the rate of secretion of various pituitary hormones, probably by an effect mediated via the hypothalamus. The administration of sodium pentobarbital (Nembutal) into rats blocks the preovulatory surge of gonadotropin and ovulation (8). Nembutal increases serum G H and prolactin levels (9, lo), whereas urethane reduces G H and prolactin (1 1).Our recent studies using antiserum toThis study was supported in part by NIH research grants AM-09094 and AM-07467, and Veterans Administration.somatostatin indicated that this tetradecapeptide is involved in a regulatory mechanism of G H and TSH secretion in rats (12).The following questions could be raised: 1. If a short feedback regulatory mechanism takes place for G H and TSH secretion, does the removal of G H and TSH by hypophysectomy affect the hypothalamic somatostatin? 2. Does the absence or the excess of circulating thyroid hormone affect the hypothalamic somatostatin? 3. Do Nembutal and urethane modify somatostatin content of the hypothalamus? Our studies were designed to answer some of these questions.Materials and methods. Experimental procedures. Young adult male rats of CD strain from Charles River were used throughout the experiments. They were maintained at a constant temperature (24") and illumination (lights on 0500-1900 hr) and were given free access to tap water and Purina laboratory chow.In Exp. I, the rats were hypophysectomized when they were 35-days old and sacrificed by decapitation 24 days or 2.5 months after the operation. Intact agematched rats served as controls.In Exp. II,7O-day-old male rats, weighing 300-350 g, were divided into the following four groups: Group 1, intact control rats; Group 2, thyroidectomized rats. These two groups were injected with 0.2 ml of 0.9% saline subcutaneously (sc). Group 3, thyroidectomized rats were injected with 0.