How does MK-677 increase growth hormone production?

Ibutamoren, also known as MK-677, is a growth hormone secretagogue. This means it stimulates the release of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) from the pituitary gland and the liver, respectively.

Ibutamoren works by mimicking the action of ghrelin, a hormone produced by the stomach that stimulates the release of GH and IGF-1. Ghrelin binds to growth hormone secretagogue receptors (GHS-R) in the pituitary gland and hypothalamus, which leads to an increase in the production and release of GH and IGF-1.

Ibutamoren also increases the release of other hormones that are involved in the regulation of metabolism, such as glucose and insulin. This can lead to an increase in muscle mass, strength, and bone density, as well as a decrease in body fat.

In addition, Ibutamoren has been found to have a positive effect on sleep, which may also contribute to its ability to increase GH and IGF-1 levels.

It has been studied in both animal models and human clinical trials, and has shown promise as a potential treatment for a variety of conditions, including growth hormone deficiency, muscle wasting, and osteoporosis. However, further research is needed to fully understand its potential benefits and risks. Additionally, the majority of the studies conducted on the substance are sponsored by the company that developed the compound.

One study found that daily oral administration of MK-677 for 12 weeks increased GH and IGF-1 levels in healthy elderly men and women. The study also found that the treatment resulted in an increase in lean body mass and a decrease in fat mass, as well as improvements in bone density. Another study found that MK-677 was able to increase GH and IGF-1 levels in adults with growth hormone deficiency (GHD). The treatment also led to an increase in muscle mass and strength, and a decrease in body fat.

It is important to note that while MK-677 is a growth hormone secretagogue, it is not a growth hormone, and its effects are different than those of exogenous growth hormone.

Overall, Ibutamoren is a synthetic compound that mimics the action of ghrelin by binding to GHS-R receptors in the pituitary gland and hypothalamus, which leads to an increase in the production and release of GH and IGF-1. This can lead to an increase in muscle mass, strength, and bone density, as well as a decrease in body fat.

1. Smith RG, Thorner MO (28 January 2000). Human Growth Hormone: Research and Clinical Practice. Springer Science & Business Media. pp. 45–. ISBN 978-1-59259-015-5.

2. ^ Smith RG, Van der Ploeg LH, Howard AD, Feighner SD, Cheng K, Hickey GJ, et al. (October 1997). "Peptidomimetic regulation of growth hormone secretion". Endocrine Reviews. The Endocrine Society. 18 (5): 621–645. doi:10.1210/edrv.18.5.0316. PMID 9331545.

3. ^ Jump up to:a b c d "Ibutamoren - Lumos Pharma/Merck". AdisInsight.

4. ^ Jump up to:a b Patchett AA, Nargund RP, Tata JR, Chen MH, Barakat KJ, Johnston DB, Cheng K, Chan WW, Butler B, Hickey G (July 1995). "Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue". Proceedings of the National Academy of Sciences of the United States of America. 92 (15): 7001–5. Bibcode:1995PNAS...92.7001P. doi:10.1073/pnas.92.15.7001. PMC 41459. PMID 7624358.

5. ^ Jump up to:a b Pong SS, Chaung LY, Dean DC, Nargund RP, Patchett AA, Smith RG (January 1996). "Identification of a new G-protein-linked receptor for growth hormone secretagogues". Molecular Endocrinology. 10 (1): 57–61. doi:10.1210/mend.10.1.8838145. PMID 8838145.

6. ^ Jump up to:a b Cassoni P, Papotti M, Ghè C, Catapano F, Sapino A, Graziani A, Deghenghi R, Reissmann T, Ghigo E, Muccioli G (April 2001). "Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines". The Journal of Clinical Endocrinology and Metabolism. 86 (4): 1738–45. doi:10.1210/jcem.86.4.7402. PMID 11297611.

7. ^ Jump up to:a b Holst B, Frimurer TM, Mokrosinski J, Halkjaer T, Cullberg KB, Underwood CR, Schwartz TW (January 2009). "Overlapping binding site for the endogenous agonist, small-molecule agonists, and ago-allosteric modulators on the ghrelin receptor". Molecular Pharmacology. 75 (1): 44–59. doi:10.1124/mol.108.049189. PMID 18923064. S2CID 2218638.

8. ^ Copinschi G, Van Onderbergen A, L'Hermite-Balériaux M, Mendel CM, Caufriez A, Leproult R, Bolognese JA, De Smet M, Thorner MO, Van Cauter E (August 1996). "Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men". The Journal of Clinical Endocrinology and Metabolism. 81 (8): 2776–82. doi:10.1210/jcem.81.8.8768828. PMID 8768828.

9. ^ Chapman IM, Bach MA, Van Cauter E, Farmer M, Krupa D, Taylor AM, et al. (December 1996). "Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects". The Journal of Clinical Endocrinology and Metabolism. 81 (12): 4249–57. doi:10.1210/jcem.81.12.8954023. PMID 8954023.

10. ^ Thorner MO, Chapman IM, Gaylinn BD, Pezzoli SS, Hartman ML (1997). "Growth hormone-releasing hormone and growth hormone-releasing peptide as therapeutic agents to enhance growth hormone secretion in disease and aging". Recent Progress in Hormone Research. 52: 215–44, discussion 244–6. PMID 9238854.

11. ^ Chapman IM, Pescovitz OH, Murphy G, Treep T, Cerchio KA, Krupa D, Gertz B, Polvino WJ, Skiles EH, Pezzoli SS, Thorner MO (October 1997). "Oral administration of growth hormone (GH) releasing peptide-mimetic MK-677 stimulates the GH/insulin-like growth factor-I axis in selected GH-deficient adults". The Journal of Clinical Endocrinology and Metabolism. 82 (10): 3455–63. doi:10.1210/jcem.82.10.4297. PMID 9329386.

12. ^ Murphy MG, Bach MA, Plotkin D, Bolognese J, Ng J, Krupa D, Cerchio K, Gertz BJ (July 1999). "Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. The MK-677 Study Group". Journal of Bone and Mineral Research. 14 (7): 1182–8. doi:10.1359/jbmr.1999.14.7.1182. PMID 10404019.

13. ^ Murphy MG, Weiss S, McClung M, Schnitzer T, Cerchio K, Connor J, Krupa D, Gertz BJ (March 2001). "Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women". The Journal of Clinical Endocrinology and Metabolism. 86 (3): 1116–25. doi:10.1210/jcem.86.3.7294. PMID 11238495.

14. ^ Smith RG, Sun Y, Jiang H, Albarran-Zeckler R, Timchenko N (November 2007). "Ghrelin receptor (GHS-R1A) agonists show potential as interventive agents during aging". Annals of the New York Academy of Sciences. 1119 (1): 147–64. Bibcode:2007NYASA1119..147S. doi:10.1196/annals.1404.023. PMID 18056963. S2CID 3220799.

15. ^ "An Anti-frailty Pill For Seniors? New Drug Increases Muscle Mass In Arms And Legs Of Older Adults". ScienceDaily. 5 November 2008.

16. ^ Jump up to:a b Copinschi G, Leproult R, Van Onderbergen A, Caufriez A, Cole KY, Schilling LM, et al. (October 1997). "Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man". Neuroendocrinology. 66 (4): 278–286. doi:10.1159/000127249. PMID 9349662.

17. ^ Meyer RM, Burgos-Robles A, Liu E, Correia SS, Goosens KA (December 2014). "A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear". Molecular Psychiatry. 19 (12): 1284–94. doi:10.1038/mp.2013.135. PMC 3988273. PMID 24126924.