Insulin-like growth factor-I and growth hormone (GH) levels in canine cerebrospinal fluid are unaffected by GH or GH secretagogue (MK-0677) administration

Elevation in circulating GH levels results in a dose-related increase in se rum insulin-like growth factor-1 (IGF-1) levels in dogs. However, it is not known whether elevations in systemic IGF-1 and GH levels contribute to the cerebrospinal fluid (CSF) levels of these hormones. Therefore, a study was designed in dogs to determine if elevated circulating GH levels was a resu lt of a GH secretagogue (MK-0677) or if exogenous GH administration resulte d in increased IGF-l and GH levels in the CSF of dogs. A total of 12 normal , young adult male dogs were randomized to three treatment groups (4 dogs/g roup) based on body weight. There were 4 vehicle control dogs. A group of 4 dogs were dosed orally with MK-0677 (5 mg/kg/day) dissolved in deionized w ater. A third group of 4 dogs received subcutaneous injections of porcine C H (pGH) at a dose of 0.1 IU/kg/day. From all dogs, blood and CSF samples we re collected prior to the initiation of treatment and on days 7 and 15 of t reatment. All samples were assayed using a validated radioimmunoassay. Admi nistration of MK-0677 or pGH resulted in a statistically significant (P les s than or equal to 0.05) increased body weight gain and increased serum IGF -1 and GH levels. In contrast, administration of MK-0677 resulted in no sig nificant (P>0.05) increase in CSF IGF-1 or GH levels on days 7 or 15 of the study. The CSF IGF-1 values ranged from 1.2 to 2.0 ng/ml with minimal vari ation among three separate samples taken during the course of the study fro m each dog. Similarly, the CSF GH levels were very low (< 0.98 ng/ml to 2.4 ng/ml) in all dogs irrespective of treatment group. This study has demonst rated that there is no correlation between the circulating levels of IGF-1 or GH and the levels of these hormones in the CSF of normal dogs. An approx imately 100-fold difference between serum and CSF IGF-1 levels in vehicle c ontrol dogs suggest that there is a blood-brain barrier for the circulating IGF-1. Similarly, failure to see an elevation in CSF GH levels despite inc reases in serum GH levels shows that there is a blood-brain barrier for GH in normal dogs. These results suggest that the likely source of GH and IGF- 1 in the CSF of dogs is from the CNS.