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 balance. A close link between leptin and pituitary hormones, including GH, has been reported. The mechanisms employed by leptin to influence somatotropes are not clear, however. Here we report a direct action of recombinant ovine leptin on primary cultured ovine somatotropes by analyzing the levels of mRNA encoding for GH or the receptors for GHRH (GHRH-R) and GH-releasing peptides (GHRP). Treatment of ovine somatotropes with leptin (10(-7)-10(-9) M) for 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 treatment of cells with leptin decreased the GH response to GHRH stimulation, but the GH response to GHRP-2 stimulation was increased. The combined effect of 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 GHRH-induced GH secretion by leptin.
Roh
S G
SG
Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia.
Nie
G Y
GY
Loneragan
K
K
Gertler
A
A
Chen
C
C
D000818:Animals; D002478:Cells, Cultured; D013007:Growth Hormone-Releasing Hormone / Q000096:biosynthesis; D019382:Human Growth Hormone / Q000096:biosynthesis / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D054411:Receptors, Leptin; D018013:Receptors, Neuropeptide / Q000096:biosynthesis; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000096:biosynthesis; D012756:Sheep; D013997:Time Factors
C515448:LEPR protein, human; D020738:Leptin; D054411:Receptors, Leptin; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; C039542:somatocrinin receptor; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C048250:somatotropin releasing hormone receptor