Oral MK-0677 Boosts IGF-I in Dogs via Pituitary Gland

Growth hormone (GH) plays a crucial role in metabolism and growth, primarily by stimulating the liver to produce insulin-like growth factor I (IGF-I). Low IGF-I levels can be associated with various conditions, including growth hormone deficiency and sarcopenia (age-related muscle loss). While many compounds aim to increase GH, the exact mechanisms of action for novel growth hormone secretagogues (GHSs) like MK-0677, particularly their dependency on the pituitary gland, were not fully understood. This study aimed to clarify if the IGF-I-boosting effects of oral MK-0677 require a functional pituitary gland.

The study found that MK-0677 effectively increased circulating IGF-I levels in intact beagle dogs. However, this effect was completely absent in beagles whose pituitary glands had been surgically removed. This demonstrated that the ability of MK-0677 to elevate IGF-I is entirely dependent on a functional pituitary gland, confirming its role as a true growth hormone secretagogue. This indicates that MK-0677 acts by stimulating the pituitary to release growth hormone, which then subsequently leads to increased IGF-I production, rather than acting directly on IGF-I synthesis or release. The observed increase in intact animals was qualitatively significant, while in hypophysectomized animals, there was no observable increase in IGF-I levels.