A Study on the Regulation of Growth Hormone Release from the Pituitaries of Rats in Vitro*

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Abstract
In vitro studies have been performed to investigate the regulation of GH release from the pituitary of rats using the synthetic pentapeptides, Tyr-DTrp-Gly-Phe-Met-NH2 (DTrp2) or Tyr-Ala-DTrp-Phe-Met-NH2 (DTrp3), and the synthetic tetradecapeptide somatostatin (SRIF). DTrp2/3 act directly on the pituitary to specifically release GH and, thus, presumably mimic the action of the putative hypothalamic native GH-releasing hormone. The GH release induced by DTrp2/3 was dose related, occurred within 5 min, and was inhibited by small amounts (10–30 ng/ml incubation medium) of SRIF. Particular emphasis has been given to the possibility that GH from the pituitary of immature rats and mature rats may be influenced differently at the pituitary level. This latter conclusion was supported by the finding that the GH released by DTrp2/3 from the pituitary of the mature rat compared to that released in the immature rat was greater in magnitude but more easily inhibited by SRIF. Other differences included: 1) progressively decreasing GH release from the pituitary of the mature but not the immature rat on repeated stimulation with DTrp2/3; 2) the addition of glucose to the incubation medium caused a partial decrease of the GH response to DTrp2/3 from the pituitary of the mature and immature rat but only inhibited the unstimulated release of GH from the pituitary of the mature rat; and 3) temporary inhibition of the DTrp2/3 pituitary GH response of SRIF of the immature compared to the mature rat was more readily reversible. For comparison, some of the above studies were also performed using the GH-releasing agents prostaglandin E1 (PGE1) and theophylline (Theo) with and without DTrp2/3 and/or SRIF. Repeated stimulation with PGEi and Theo but not DTrp2/3 elicited a sustained release of GH from the pituitary of the mature rat; adding PGEi or Theo with DTrp2/3 elicited a greater release of GH when the DTrp2/3 GH response alone was usually decreased during the last 2 h of a 6-h incubation. In contrast to the DTrp2/3 GH response, the PGEi and Theo GH responses were immediately reversible after temporary inhibition with SRIF. Other conclusions from these studies were: 1) DTrp2/3 may be unique pentapeptides for learning more about the function and behavior of the putative GH-releasing hormone receptor of the pituitary somatotrophs; 2) the dual effects of SRIF plus DTrp2/3 rather than the effect of SRIF alone appear to produce an irreversible inhibition of the stimulated release of GH at the putative GH-releasing hormone-SRIF receptor(s); and 3) studies on the regulation of GH release in vitro from the pituitaries of immature and mature rats may reveal certain unique differences which have important physiological implications in vivo.