The in vitro effect of leptin on growth hormone secretion from primary cultured ovine somatotrophs

Although existing data suggest an influence of leptin on circulating levels of growth hormone (GH), the action site and properties of leptin are still controversial, Using primary cultured ovine pituitary cells, we studied th e direct effect of leptin on the secretion of CH, Pituitary cells were diss ociated by collagenase and subjected to Percoll gradient centrifugation to enrich the somatotroph population to 60-80% of cells. Treatment of primary cultured ovine somatotrophs with leptin (10(-9)-10(-7) M) for 30 min did no t affect basal, GH-releasing hormone (GHRH) (10(-7) M)- or GH-releasing pep tide-2 (GHRP-2)(10(-7) M)-stimulated GH secretion. Following treatment of c ells for 1-3 d with leptin, GHRH-stimulated GH secretion was reduced and GH RP-2-stimulated GH secretion increased. The combined effect of GHRH and GHR P-2 on GH secretion was not altered by the treatment of cells with leptin f or 3 d, GHRH receptor mRNA levels in cultured somatotrophs were decreased b ut GHRP receptor mRNA levels were increased by 3-d leptin treatment. These results suggest that leptin has a longterm effect on somatotrophs to reduce GHRH receptor synthesis leading to a decrease in GHRH-stimulated GH secret ion, Leptin appears, however, to have an opposite effect on GHRP receptor s ynthesis leading to an increase in GHRP-stimulated GH secretion.