Obesity-associated decrease in growth hormone-releasing hormone gene expression: a mechanism for reduced growth hormone mRNA levels in genetically obese Zucker rats.

The secretion of growth hormone (GH) is impaired in the genetically obese Zucker rat where GH gene expression and plasma GH levels are depressed; however, the underlying mechanism of this abnormality remains unclear. We have evaluated the potential causative role of hypothalamic GH-releasing hormone (GHRH) and somatostatin (SRIH) gene expression in the onset of the decreased GH mRNA levels by studying both GHRH and SRIH mRNA and peptide levels in obese and lean rats at 5 weeks of age when the decrease in GH mRNA is first detected. At that age both GHRH content and GHRH mRNA were significantly reduced in obese rats as compared to lean controls; hypothalamic SRIH content was also decreased in obese rats, but SRIH mRNA levels did not differ. Since GHRH is capable of stimulating GH gene expression, the decreased GHRH mRNA level could be a critical factor in causing the attenuation in GH gene expression and consequent diminution of circulating plasma GH.