A POSSIBLE ROLE OF HYPOTHALAMIC SOMATOSTATIN IN THE MAINTENANCE OF RAT PITUITARY-RESPONSIVENESS TO GROWTH HORMONE-RELEASING FACTOR

To characterize the role of hypothalamic somatostatin (SRIF) in regulating pituitary responsiveness to GH- releasing factor (GRF) in vitro, we reduced SRIF input to the rat anterior pituitary through the portal vessels. Three different paradigms were used as follows: 1) anterolateral hypothalamic deafferentation, 2) electrolytic lesions of the periventricular nucleus, and 3) passive immunization with SRIF antiserum. Rat CRF content in the stalk-median eminence markedly decreased to 19% and 57% of that of sham-operated controls 10 days after the deafferentation and the lesions, respectively. In contrast, rat GRF content was unchanged by either operation. SRIF content markedly decreased to 78%, 12%, and 2% of the control level 1, 3, and 10 days after deafferentation, respectively, and to 48% and 8%, 1 and 10 days after the lesions, respectively. The serum GH concentration was significantly increased 1 and 3 days after the deafferentation (P < 0.01) and also 1 day after the lesions (P < 0.01), followed by no increase 10 days after either operation. Anterior pituitary weight and GH content markedly decreased 3 and 10 days and 10 days after the deafferentation and the lesions, respectively. The human GRF (0.1 μM)-induced GH release response of anterior pituitaries removed from these treated rats was examined in an in vitro perifusion system. Even 1 day after these treatments, GH responsiveness was clearly attenuated by anterolateral hypothalamic deafferentation (8.61 ± 0.78 vs. 3.62 ± 0.54 μg GH/h; P < 0.01), periventricular nucleus lesions (6.52 ± 1.07 vs. 3.20 ± 0.53 μg GH/h; P < 0.01) and passive immunization with SRIF antiserum (5.80 ± 0.43 vs. 2.54 ± 0.16 μg GH/h; P < 0.01). This attenuated responsiveness gradually deteriorated 3 and 10 days after the surgical operations. These results indicate that SRIF neurons in the anterior periventricular nucleus play a role in maintaining the pituitary responsiveness to GRF, in addition to the original action of inhibiting GH release. © 1990 by The Endocrine Society.