MK-677 (Ibutamoren) and IGF‑binding proteins

Main points: Ibutamoren raises circulating IGF‑1 by altering IGF‑binding proteins, notably IGFBP‑3. Its action stimulates the GH–IGF‑1 axis, increasing secretion of growth hormone, IGF‑1, and the family of IGF‑binding proteins (IGFBP‑1 through IGFBP‑6). Studies report no meaningful shifts in cortisol, prolactin, thyroid hormones, or insulin, suggesting a fairly specific effect on the GH–IGF‑1 pathway without disturbing other endocrine axes. The effects on each IGFBP can vary, but overall MK‑677 modulates the IGF system and thus the availability and activity of IGF‑1. IGFBPs extend IGF’s circulatory half‑life and can prevent IGF from binding the insulin receptor. IGFBP‑3 is the most plentiful IGFBP in blood and binds IGF‑1 and IGF‑2 with similar affinity. Beyond IGF binding, IGFBP‑3 has IGF‑independent roles: it influences angiogenesis, contributes to mechanisms that inhibit prostate cancer, is involved in DNA damage repair, and can trigger autophagy in bronchial epithelial cells. IGFBP‑3 also interacts with receptors such as RXR‑α, PPAR‑γ, the vitamin D receptor and Nur77, which helps explain some of its pro‑apoptotic effects — stopping damaged cells from dividing, clearing unhealthy cells, and supporting tissue renewal. Dose response: the referenced study showed a dose‑dependent rise in GH and IGF‑1, with larger increases seen at higher doses (0.8 mg/kg/day). Further research...