GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
Ghrelin misbalance affects mice embryo implantation and pregnancy success by uterine immune dysregulation and nitrosative stress.
Luque. Eugenia Mercedes EM; Díaz-Luján. Cintia María CM; Paira. Daniela Andrea DA; de Loredo. Nicolás N; Torres. Pedro Javier PJ; Cantarelli. Verónica Inés VI; Fretes. Ricardo R; Motrich. Rubén Darío RD; Martini. Ana Carolina AC
Key Findings
- Blocking ghrelin with (D‑Lys3)GHRP‑6 raised embryo loss and increased uterine eNOS, iNOS, and nitrotyrosine (markers of nitrosative stress).
- Both ghrelin excess and antagonist treatment boosted pro‑inflammatory cytokines (IL‑6, IL‑17, MMP‑9) and reduced the anti‑inflammatory IL‑10.
- Immune cell changes included more NK cells and CD11b+ dendritic cells and fewer T‑cells in the uterus.
Practical Outcomes
- For biohackers using GHRP‑6, the study suggests caution if you are pregnant or trying to conceive, as altering ghrelin signaling could harm embryo implantation. It also highlights that ghrelin modulation can affect inflammation and oxidative stress, which may be relevant for overall health but does not provide a direct performance or longevity protocol.
Summary
In pregnant mice, both too much ghrelin and blocking ghrelin with the peptide (D‑Lys3)GHRP‑6 caused more embryos to be reabsorbed (lost) and created a noisy, inflammatory environment in the uterus. This was linked to higher levels of nitric‑oxide‑producing enzymes and inflammatory signals, as well as shifts in immune cells.
Abstract
In a previous study we found that ghrelin (Ghrl) misbalance during the peri-implantation period significantly impaired fetus development. In this study we aimed to evaluate the putative mechanisms underlying these effects, including embryo implantation success, uterine nitric oxide synthase (NOS) activity, nitric oxide synthesis and the inflammatory/immune uterine profile. Ghrelin misbalance was induced by injecting 4nmol/animal/day of Ghrl (hyperghrelinemia) or 6nmol/animal/day of a Ghrl antagonist (Ant: (D-Lys3)GHRP-6) from day 3 to 8 of pregnancy. Control animals (C) were injected with de vehicle. Females were euthanized at pregnancy day 8 and their uteri excised in order to evaluate: the percentage of reabsorbed embryos (microscopically), eNOS, iNOS and nytrotirosine expression (by immunohistochemistry), nitrite synthesis (by Griess technique), VEGF, IL-10, IL-17, IL-6, MMP9 and GM-CSF expression (by qPCR) and leukocyte infiltration by flow cytometry (evaluating T cells, NK cells, granulocytes, dendritic cells and macrophages). Ant-treatment significantly increased the percentage of reabsorbed embryos and the uterine expression of eNOS, iNOS and nytrotirosine. (D-Lys3)GHRP-6-treatment increased also the expression of the inflammatory cytokines IL-6, IL-17 and MMP9, and decreased that of IL-10 (anti-inflammatory). Moreover, Ant-treatment increased also the NK cells population and that of CD11b<sup>+</sup> dendritic cells; and decreased T cells percentages. Similarly, hyperghrelinemia showed a significant increase vs. C on eNOS, iNOS and nytrotirosineuterine expression and a decrease in T cells percentages. Ghrl misbalance during the peri-implantation period induces pro-inflammatory changes and nitrosative stress in the gravid uterus, impairing significantly embryo implantation and/or development.
Study Information
pubmed
2023
2023-12-01T00:00:00.000Z
10.3389/fendo.2023.1288779
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