Characterization of rat hypothalamic growth hormone-releasing factor

Abstract

The importance of the hypothalamus in the regulation of growth hormone (GH) secretion from the adenohypophysis has been supported by experimental and clinical evidence^1–3. It has been observed that GH secretion is in part controlled by hypothalamic GH release-inhibiting factors⁴, two forms of which, somatostatin-14 (ref. 5) and somatostatin-28 (refs 6–9), have been characterized. Peptides with GH-releasing activity were recently purified from two human pancreatic tumours of acromegalic patients and characterized^10–14. Synthetic versions of these human pancreatic tumour GH-releasing factors (hpGRFs) were found to be potent GH secretagogues in vitro^11,12,15 and in vivo^12,16,17 and to exhibit actions and interactions similar to those observed with partially purified hypothalamic GRF¹². GH-releasing peptides have been purified from hypothalami of various species^4,15,18,36 but the structure of natural hypothalamic GRF has not yet been reported¹⁹. We now describe the purification, sequence analysis and synthesis of a 43-residue polypeptide isolated from rat hypothalamic extracts on the basis of its ability to stimulate GH secretion from cultured rat adenohypophyseal cells. The native polypeptide and its synthetic replicate do not differ significantly in their biological potencies and intrinsic activities. We propose that this polypeptide, which shows 67% homology with the corresponding N-terminal 43 residues in hpGRF-44, is the long-sought rat hypothalamic GRF (rhGRF).