Growth-hormone-releasing peptide fragment (rat GRF 1-29)

What this is

GRF (1-29) amide (rat) is a synthetic 29-residue peptide corresponding to the N-terminal fragment of rat growth hormone-releasing factor (GRF, also called growth hormone-releasing hormone or GHRH). Full-length rat GRF is a 43-amino-acid hypothalamic peptide that stimulates growth hormone (GH) release from the anterior pituitary (Böhlen, Biochem Biophys Res Commun, 1984). The 1-29 fragment is the shortest sequence that retains the full GH-releasing potency of the parent hormone (Ling, Annu Rev Biochem, 1985), and the C-terminal amide cap (–NH₂, absent from the raw 29-letter sequence) is added during synthesis to protect against carboxypeptidase cleavage. The peptide is used in laboratory research to probe GHRH-receptor signaling and as the structural template for human GRF (1-29) analogs.

History

Hypothalamic GRF was identified in the early 1980s after pancreatic-tumor extracts that ectopically secreted a GH-releasing factor allowed Guillemin's and Vale's groups to purify and sequence it. Rat hypothalamic GRF was then isolated directly from ~35,000 rat hypothalami by acid extraction, immunoaffinity chromatography, gel filtration, and reverse-phase HPLC, and characterized as a 43-residue peptide (Böhlen, Biochem Biophys Res Commun, 1984). Structure–activity work in the same period (Ling, Annu Rev Biochem, 1985) established that the N-terminal 1-29 fragment is sufficient for full intrinsic activity at the GRF receptor, making the (1-29) amide the standard working form for biochemical and pharmacological studies of the GHRH system. Related GRF-family peptides were subsequently isolated from non-mammalian species, including a 45-residue GRF-like peptide from common carp hypothalamus (Vaughan, Neuroendocrinology, 1992).

What it does

In vivo and in cultured pituitary cells, rat GRF (1-29) amide binds the growth hormone-releasing hormone receptor on somatotrophs in the anterior pituitary and triggers release of stored growth hormone. The receptor is a class B G-protein-coupled receptor; the same receptor is engaged in rats by full-length GRF (1-43) and in humans by the homologous human GHRH and its 1-29 fragment (sermorelin) (Jetté, Endocrinology, 2005). The 1-29 fragment is short-acting: proteolytic degradation in rat pituitary and hypothalamus tissue homogenates gave apparent half-lives of 22 ± 3 minutes and 25 ± 4 minutes, respectively (Boulanger, Brain Research, 1993). This short half-life is the rationale behind albumin-conjugated and N-terminally modified analogs developed later to extend in vivo duration of action.

Evidence

• Human: No human trials of the rat-sequence peptide. The homologous human GRF (1-29) amide (sermorelin) was studied clinically and previously approved as a GH-secretagogue.
• Animal: Stimulates GH release in rats and serves as the standard reference compound in rodent GHRH-system pharmacology; tissue-degradation kinetics characterized (Boulanger 1993).
• In vitro: Equipotent with full-length rat GRF in stimulating GH release from anterior pituitary cell preparations; basis for downstream analog development (Ling 1985; Jetté 2005).

Related peptides

• Sermorelin — the human GRF (1-29) amide analog and clinical counterpart of this rat-sequence research peptide.
• CJC-1295 — an albumin-conjugating modified human GRF (1-29) analog developed to extend duration of action at the same GHRH receptor (Jetté, Endocrinology, 2005).
• Tesamorelin — a stabilized human GRF (1-44) analog acting at the same receptor.