Somatostatin in concentrations of 10-6 to 10-8 M inhibited basal release of thyrotropin releasing factor in organ culture of rat hypothalamus. Norepinephrine in doses of 10-4-10-6 M induced release of thyrotropin releasing factor which increased progressively with time and was temperature and dose dependent. This enhanced thyrotropin-releasing-factor release was inhibited by somatostatin at 10-6-10-8 M. The tetradecapeptide somatostatin, which is extensively distributed throughout the central nervous system, gastrointestinal tract, and pancreas (1-3), inhibits release of various hormones including growth hormone (4), thyrotropin (5), glucagon (6) and insulin (4). Somatostatin infusion lowers circulating thyrotropin in man (7), and passive immunization of rats with specific somatostatin antiserum increases basal and thyrotropin releasing factor (TRF)-stimulated thyrotropin secretion (8). These experiments imply an interrelationship between TRF and somatostatin and pituitary thyrotropin secretion. Potential local effects of somatostatin within the hypothalamus itself, either directly on peptide hormone secretion or via an action upon neurotransmitters, are equally likely and have not been critically examined.Studies of the regulation of TRF synthesis and release are complicated by the fact that the hormone is widely distributed throughout the central nervous system so that measurements of the hormone in the peripheral blood, regardless of their accuracy, may not faithfully mirror concentrations of TRF actually delivered to the anterior pituitary (9). Moreover, measurements of hormone levels in the hypophyseal portal circulation require surgical cannulation under anesthesia which entails the administration of anesthetics, many of which affect hypothalamic hormone release (10), and in most instances measurements require prior hypophysectomy as well, to permit sampling of the entire hypothalamic outflow (11). Our own approach has been to utilize short-term organ culture of rat hypothalamus as a model for delineating factors modulating in vitro release of TRF. We have found that somatostatin at 10-6 M-10-8 M inhibits basal release of TRF. Moreover, norepinephrine (NE) in doses of 10-4-10-6 M increases release of TRF, an effect which is not seen in the presence of somatosta- were killed by decapitation at 10-11 a.m. After the brain was exposed by removal of the skull with sterile instruments, it was carefully placed in a sterile plastic petri dish which contained Ca2+, Mg2+-free Hanks' balanced salt solution, bacitracin (2.1 X 10-5 M), and glucose (6 mg/ml). Prior to use the dishes had been "gassed" with 5% C02/95% air. Dissection was performed in a laminar flow hood with sterile instruments at a plane 1 mm lateral to the midline and at a depth of 1 mm. The fragments were obtained from the area between the posterior margin of the optic chiasm and the anterior portion of the mammillary body. Microscopic examination (Fig. 2) demonstrated that the fragments included parts of the paraventricular, dorsomedial, vent...