The major problem of the therapy based on hGH-RH or hGH-RH-(1-29)-NH₂ is their susceptibility to enzyme cleavage. To overcome this problem several hGH-RH-(1-29)-NH₂ analogues have been obtained by these authors [1]. Analogues containing homoarginine (Har) or Orn instead of Arg and Lys were completely resistant to trypsin. Two of these analogues, namely [Dat¹,Har^11,12,20,29,Ala¹⁵,Nle²⁷,Asp²⁸]-hGH-RH-(1-29)-NH₂ (1) and [Dat¹,Har^11,20,29,Orn^12,21,Ala¹⁵,Nle²⁷,Asp²⁸]-hGH-RH-(1-29)-NH₂ (2) were about 50 times as potent as hGH-RH-(1-29)-NH₂ itself in vivo.

To get insight into the process of releasing GH we examined stimulation of cultured pituitary cells with 1 and 2. The level of GH was measured with RIA methods after 30, 60, 120, and 240 minutes using hGH-RH-(1-29)-NH₂ and its analogues in doses 1, 10 and 100 nM. The profile of GH release indicated that analogues were more active then hGH-RH-(1-29)-NH₂. The maximal effects of the analogues was after 60 minutes of incubation, and was still noticeably higher after 240 minutes.

These results indicate that duration of cell stimulation may be one of the reasons of incrased activity in vivo. It is also implies that the used procedure can be useful for preliminary evaluation of new GH releasing substances.

References:

[1] Izdebski J., Witkowska E., Kunce D., Orłowska A., Baranowska B., Wolińska-Witort E., J.Peptide Sci. 2004, 10, 524-529.

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