Historical Background

Between 1976-1980, during the development of GHRPs, a major impetus for the search was an unequivocal belief in the existence of a native (GHRH) in spite of the frustrations of unsuccessful, herculean efforts over a 15-year period (1962-1976). Interestingly, GH releasing activity was demonstrated in more than one partially purified fraction of porcine hypothalamic extracts, suggesting that perhaps more than one GHRH factor existed (2-5).

Listed in Table 1 are the major GHRP milestones in chronological order. The first GHRP (DTrp2) was developed in 1976 (4,5). The amino-acid sequence is recorded in Table 2. Although DTrp2 was not potent and was inactive in vivo, it released GH by a direct action on the pituitary. In addition, the GH action was specific in that LH, FSH, TSH, and PRL were not released (Fig. 1). This DTrp2pentapeptide, TyrDTrpGlyPheMetNH2, evolved from the natural opiate Met enkephalin pentapeptide, TyrGlyGlyPheMet. Opiates and opiate peptides release GH via a hypothalamic action but not via a direct pituitary action. Furthermore DTrp2 had no opiate activity.

From: Human Growth Hormone: Research and Clinical Practice Edited by: R. G. Smith and M. O. Thorner © Humana Press Inc., Totowa, NJ

Table 1 Major GHRP Milestones

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