Endocrine Abstracts

Ghrelin is a novel growth hormone-releasing peptide, recently identified in the rat stomach as the endogenous ligand for the growth hormone secretagogue-receptor (GHS-R). Previously, regulation of GH release was thought to occur primarily via a phasic interaction between two hypothalamic neuropeptides, GHRH and somatostatin. It is now thought that ghrelin is an important third factor in the regulatory pathway. In addition to its GH-releasing activity ghrelin may have other actions, including effects on the hypothalamo-pituitary adrenal axis, on feeding, the heart, and on cell proliferation. We have investigated the tissue distribution of the mRNA for ghrelin and its receptor in a variety of normal tissues. Total RNA was extracted from the tissue and semi-quantitative polymerase chain reaction (RT-PCR) was performed, using intron-spanning primers for ghrelin, GHS-R, and GAPDH. Ghrelin was distributed in a wide range of normal human tissues: fundus, jejunum, pancreas, spleen, lymph node, breast, antrum, duodenum, adrenal, left colon, ileum, thyroid, gall bladder, liver, ovary, oesophagus, skin, kidney, striated muscle, fat, right colon, fallopian tube, pituitary, placenta, and lung (in order of decreasing ghrelin/GAPDH ratio). The receptor was predominantly found in the brain and pituitary. Specifically, GHS-R was predominantly expressed in the brain, pituitary and, at much lower levels, in the adrenal gland.

In conclusion, the predominantly central expression of GHS-R probably relates to its central effects and particularly its neuroendocrine effects on GH release, while the significance of the widespread tissue distribution of ghrelin remains to be determined. The discordance between the widespread distribution of ghrelin, and the highly limited distribution of its receptor, suggests that ghrelin may act upon novel subtypes of GHS-R in as yet unidentified physiologic role(s), separate from or in conjunction with its central activity.