Suppressing effects of short-chain fatty acids on growth hormone (GH)-releasing hormone-induced GH release in isolated anterior pituitary cells of goats

The involvement of tetrodotoxin-sensitive Na+ channels and receptor-operate d nonspecific Ca2+ channels, and the effects of short-chain fatty acids, on growth hormone (GH) release induced by GH-releasing hormone (GHRH) were in vestigated in cultured and freshly isolated caprine anterior pituitary cell s. In 3-d cultured cells in Dulbecco's modified Eagle's medium, an increase in GH release induced by GHRH (10 nmol/l) was moderately, but significantl y, reduced by a voltage-sensitive Na+ channel antagonist tetrodotoxin (1 mu mol/l). The GHRH-induced GH increase, which was not affected by a simultan eous addition of a receptor-operated nonspecific Ca2+ channel antagonist te tramethrine (0.1 mmol/l), was significantly reduced by a voltage-sensitive L-type Ca2+ channel antagonist nifedipine (1 mu mol/l). Propionate and buty rate at 10 mmol/l,however, not only suppressed basal GH release but also si gnificantly reduced the GH increase induced by 10 nmol/l of GHRH. The inhib itory action of these acids was also reproduced by an addition of beta-hydr oxy butyrate (10 mmol/l) and octanoate (10 mmol/l). In freshly isolated and perifused cells, butyrate (10 mmol/l) as well as somatostatin (100 nmol/l) significantly reduced the GH increase induced by GHRH. From these findings we conclude that tetrodotoxin-sensitive Na+ channels an d voltage-dependent L-type Ca2+ channels are involved in the cellular mecha nism for GHRH-induced GH release, and that short-chain fatty acids such as propionate and butyrate have a direct action on somatotrophs to reduce basa l and GHRH-induced GH release, in caprine somatotrophs. (C) 1999 Elsevier S cience Inc. All rights reserved.