High plasma growth hormone (GH) levels inhibit expression of GH secretagogue receptor messenger ribonucleic acid levels in the rat pituitary

Synthetic GH secretagogues (GHSs) act via a receptor (GHS-R) distinct from that of GH-releasing hormone. The GHS-R has been cloned from the pituitary and is expressed not only in the pituitary but also in specific areas of th e brain, including the hypothalamus. Recent studies suggest that hypothalam ic GHS-R expression is regulated by GH. This study was designed to investig ate whether pituitary GHS-R expression is modulated by GH. Female Wistar-Fu rth rats were injected sc with either saline (control) or GC tumor cells (G C) that secrete rat GH. The tumors were allowed to develop for 1-4 weeks. A t weeks 1-4, control (n = 4-8) and GC rats (n = 3-8) were killed. Pituitary GHS-R messenger RNA (mRNA) was measured by a quantitative competitive PCR assay. The endogenous GHS-R mRNA levels were measured by determining the am ount of competitive template RNA required to produce equimolar amounts of n ative and competitive template PCR products. The mean log plasma GH levels were significantly greater in the GC rat group than in the control group at weeks 2, 3, and 4. At these times, the mean log pituitary GHS-R mRNA conte nts were significantly lower in the GC rat group than in the control group. No relationship could be established between log estradiol levels and GHS- R levels. These data indicate that pituitary GHS-R expression is modulated by GH.