The regulation of growth hormone (GH) secretion involves hypothalamic somatostatin and its specific receptors (sst1-sst5). sst1 is highly expressed in the arcuate nucleus (AN), and several data suggest that sst1 receptors are preferentially involved in the somatotropic hypothalamic network. Neuropeptide Y (NPY)-containing neurons function as direct transducers for GH feedback. Interestingly, there is an overlap in the distribution of NPY and sst1 containing cells in the AN. To determine whether these NPY cells are target for somatostatin we used a double label in situ hybridization histochemistry. Image analysis revealed that approximately 7% of NPY-hybridizing neurons coexpressed sst1 mRNA. These results further support the evidence for the direct interactions between the somatotropic axis and the neuroendocrine regulatory loops of energy homeostasis.

Intrauterine growth restriction (IUGR) is one of the major causes of short stature in childhood. Abnormalities in the growth hormone (GH) axis have frequently been observed in children who are born intrauterine growth restricted and GH treatment is effective to improve final height. However, the way that the GH axis is involved is not fully understood. Previously, when investigating the effect of IUGR on the central somatotrophic axis, a hypothalamic effect was discovered with elevated somatostatin and decreased neuropeptide Y mRNA expression levels, whereas serum GH and insulin-like growth factor I (IGFI) were unaltered. These findings were thought to indicate a hypothalamic alteration of the GH axis due to IUGR, probably to compensate pituitary output, thereby normalising peripheral values of GH and IGFI. Therefore, the present study aimed to evaluate the effect of IUGR on the pituitary GH axis in this rat model. Pups from rats that underwent bilateral uterine artery ligation at day 17 of pregnancy were studied. Pituitary glands were collected from 1-year-old offspring for quantitative measurements of GH, GH-receptor (GH-R), GH-releasing hormone receptor (GHRH-R), somatostatin receptor subtype 2 and 5, IGFI and IGFI receptor mRNA levels using a real-time reverse transcriptase-polymerase chain reaction. In addition, liver GH-R and IGFI mRNA expression levels were measured and a radioimmunoassay was performed to determine serum IGFI levels. In the IUGR rat, levels of pituitary GH, GH-R and GHRH-R relative gene expression (RGE) were increased. No differences were found in the RGE level of all other pituitary growth factors, liver GH-R and IGFI, and serum IGFI concentration between IUGR and control rats. The present data show that intrauterine growth failure leads to changes in the pituitary that might counterbalance the effects found previously in the hypothalamus.