HYPOTHALAMIC REGULATION OF GROWTH HORMONE (GH) SECRETION

Abstract

A physiological role of somatostatin (SRIF) on GH-releasing factor (GRF) -induced GH secretion was examined by utilizing in vitro perifusion systems. The following three experiments were carried out.1. GRF-induced GH release was examined in whole anterior pituitaries from rats subjected to the following treatments : 1) anterolateral hypothalamic (ALH) deafferentation, 2) lesions of the hypothalamic periventricular nucleus (Pe) and 3) passive immunization with anti-SRIF serum. The response of these pituitaries to human (h) GRF (0.1 μM) stimulation was markedly attenuated within a day, accompanied by a significant decrease in SRIF content in the stalk-median eminence from rats with ALH deafferentation and Pe lesions. Also SRIF in the SME significantly decreased after the ALH cut or Pe lesions, whereas hGRF remained constant even 10 days after the operations. These data suggest that SRIF in vivo plays a significant role in the anterior pituitary in maintaining hGRF-GH response in vitro.2. The effects of SRIF infusion on successive GH release in response to GRF were examined in an in vitro system as in Exp. 1. Two hours after the first GRF (0.1 μM) stimulation, the response to the second stimulation was markedly attenuated. But this was not observed when the pituitaries were subjected to the second stimulation after a 3 hour interval. In contrast, when SRIF (0.1 μM) was infused for 50 min 1 h after the first stimulation to lower basal GH release, the second response to hGRF was restored to the level of the first response. To determine whether SRIF exerts a direct action on the GH response, a prestimulatory perifusion with SRIF (0.1 μM) for 50 min was tested. The treatment tended to facilitate the pituitary response to hGRF. When pretreated with SRIF for 50 min at a lower concentration (0.05 μM), the response to the first hGRF (0.05 μM) stimulation was significantly facilitated. These data suggest that 1) SRIF perifusion rapidly restores the attenuated response to a second hGRF challenge by lowering GH release to basal levels and 2) SRIF pretreatment facilitates the GH response to the first hGRF stimulation.3. The facilitation by SRIF of hGRF-induced GH response of dispersed pituitary cells was further characterized and analyzed. SRIF-pretreatment (1.0 nM) also caused a marked facilitation of the hGRF (1.0 nM) -GH response which continued for 30 min after SRIF withdrawal. Although a significant “rebound increase” in GH release was observed within 15 min after SRIF withdrawal, the amount was much less than in the hGRF-GH response. Both DbcAMP (1.0 mM) -and KCl (15 mM) -induced GH release response were significantly facilitated by SRIF pretreatment. However, cAMP production by hGRF was not increased but significantly decreased by SRIF pretreatment. Thus SRIF facilitation of hGRF-GH release is thought to take place in the process after cAMP formation.From the results of these experiments, it is concluded that 1) SRIF is required for the maintenance of the pituitary response to GRF, 2) SRIF pretreatment facilitates GRF-induced GH release.