Effect of GHRH and GHRP-2 treatment in vitro on GH secretion and levels of GH, pituitary transcription factor-1, GHRH-receptor, GH-secretagogue-receptor and somatostatin receptor mRNAs in ovine pituitary cells.
Yan. Ming M; Hernandez. Maria M; Xu. Ruwei R; Chen. Chen C
Key Findings
- GHRH (10 nM) and GHRP‑2 (100 nM) each raise GH mRNA and secreted GH within 0.5–2 hours, and the combination works synergistically.
- Both peptides increase Pit‑1, GHRH‑R and GHS‑R mRNA early (0.5 h), indicating rapid activation of the GH production pathway.
- GHRH raises somatostatin‑1 (sst‑1) receptor mRNA, while GHRP‑2 suppresses both sst‑1 and sst‑2 receptors, suggesting opposite effects on the inhibitory GH pathway.
Practical Outcomes
- These results support the idea that using GHRP‑2 together with GHRH can more effectively stimulate GH release than either alone. For self‑experimenters, timing (short‑term exposure) and modest doses (nanomolar range) appear sufficient to trigger cellular changes. However, because the work is in sheep cells in a dish, human dosing and safety still need real‑world validation before applying these protocols.
Summary
In sheep pituitary cells, both GHRH and the peptide GHRP‑2 boost the production and release of growth hormone (GH). They also quickly change the levels of several receptors and transcription factors that control GH, showing how the two compounds work together at the cellular level.
Abstract
Growth hormone (GH)-releasing hormone (GHRH) and GH-releasing peptides (GHRPs) stimulate the release of GH through their specific receptors on somatotropes. Combined GHRH and GHRP administration causes a synergistic GH release in vivo by an unknown mechanism. The current study focuses on the direct action of GHRH and GHRP on several molecular targets in somatotropes. To clarify the mechanism of action, ovine somatotropes were used to measure the expression of mRNAs encoding for GH, pituitary transcription factor-1 (Pit-1), GH-secretagogue receptor (GHS-R), GHRH-R, somatostatin receptor subtypes (sst-1 and sst-2) and GH release after GHRH and GHRP-2 treatment for 0.5, 1, 1.5 and 2 h. GHRH (10 nM), GHRP-2 (100 nM) and combined GHRH-GHRP-2 increased the levels of GH mRNA and GH release from 0.5 to 2 h in a time-dependent manner. The levels of Pit-1, GHRH-R and GHS-R mRNA were increased after 0.5 h treatment of cells with GHRH and GHRP-2. The levels of sst-1 but not sst-2 mRNA were significantly increased after 0.5 and 1 h of GHRH treatment. In contrast, both sst-1 and sst-2 mRNA expression was inhibited after 0.5-2 h of GHRP treatment. These data demonstrate a direct in vitro modification of ovine somatotropes by GHRH and GHRP-2 resulting in altered GHRH-R, GHS-R, Pit-1, sst-1, sst-2 and GH gene expression; this may underlie the regulatory action of GHRH and GHRP-2 on GH secretion.
Study Information
pubmed
2004
10.1530/eje.0.1500235