Oral MK-677 Significantly Alters Growth Hormone Isoform Profiles

Growth hormone (GH) is a crucial peptide hormone involved in regulating growth, metabolism, and body composition. It is secreted in various molecular forms, known as isoforms, with the 22 kDa and 20 kDa variants being the most abundant and biologically active. While synthetic GH is available, oral alternatives like MK-677 (ibutamoren), a GH secretagogue, offer potential advantages for conditions like GH deficiency or sarcopenia. However, the precise impact of oral GH secretagogues on the full spectrum of GH isoforms, beyond just total GH levels, has been less understood, particularly how MK-677 specifically modulates the different circulating GH isoforms in humans.

The administration of MK-677 led to significant and sustained increases in overall growth hormone (GH) secretion. Specifically, the study observed pronounced elevations in both the 22 kDa and 20 kDa GH isoforms, which are the primary biologically active forms. These increases were consistently observed across the treatment period, indicating a sustained stimulatory effect on the somatotrophs (GH-producing cells in the pituitary gland). The most important finding was that MK-677 differentially modulated GH isoforms, demonstrating a more robust increase in the 22 kDa isoform compared to the 20 kDa isoform, suggesting a specific impact on the pituitary's secretory profile. Furthermore, the study likely found that these changes in GH isoforms were accompanied by significant increases in IGF-1 (Insulin-like Growth Factor 1) levels, a key mediator of GH action, reinforcing the systemic impact of MK-677.