Direct modification of somatotrope function by long-term leptin treatment of primary cultured ovine pituitary cells

Leptin is produced primarily in adipocytes and regulates body energy balanc e. A close link between leptin and pituitary hormones, including GH, has be en reported. The mechanisms employed by leptin to influence somatotropes ar e not clear, however. Here we report a direct action of recombinant ovine l eptin on primary cultured ovine somatotropes by analyzing the levels of mRN A encoding for GH or the receptors for GHRH (GHRH-R) and GH-releasing pepti des (GHRP). Treatment of ovine somatotropes with leptin (10(-7)-10(-9)m) fo r 1-3 d reduced the mRNA levels encoding GH and GHRH-R, but increased GHRP receptor mRNA levels in a time- and dose-dependent manner. Three-day treatm ent of cells with leptin decreased the GH response to GHRH stimulation, but the GH response to GHRP-2 stimulation was increased. The combined effect o f GHRH and GHRP-2 on GH secretion was not altered by treatment of the cells with leptin. These results demonstrated a direct action of leptin on ovine pituitary cells, leading to a reduced sensitivity of somatotropes to GHRH. It is also suggested that GHRP may be useful to correct the decrease in GH RH-induced GH secretion by leptin.