Endocrine Abstracts

GH concentrations are high at birth but it is unclear whether and where GH signaling takes place at this time. We assessed the response to GH in young normal and GH-deficient (GHD) pups.

Transgenic M2-GRF mice were significantly GHD from birth. Weight and plasma IGF1 concentration were normal, but reduced at 6–8 day of age (P<0.01). 3 and 10-day-old GHD and normal (WT) mice were treated with bovine GH (bGH, 10 μg/g bw s.c. bd) or vehicle for 5 day (n=5–8/group). Ten day old GHD mice, but not WT mice, responded by increasing weight gain (P=0.01), tibial length (P=0.02) and plasma IGF1 (P<0.05). In contrast, these parameters were unaffected in response to bGH in 3-day-old GHD mice (P>0.05). A single mouse GH (mGH) injection (1 μg/g bw i.p.) in GHD mice induced Stat5 signaling in liver and growth plate 25 min later, at both 0 and 7 day of age. When 7-day-old GHD and WT mice were killed at various times, GHD mice (n=12) had undetectable plasma GH-concentration and no detectable pY-Stat5 in the liver. In 21 WT mice, GH-concentrations ranged from 4.1–55.2 ng/ml. Hepatic pY-Stat5 was detected in eight mice, and these mice had significantly higher plasma GH concentrations (24.4±5.0 vs 9.1±1.0 ng/ml, P=0.001), and pY-Stat5 staining was most intense in the mice with the highest GH-concentration.

In conclusion, 10-day-old but not 3-day-old GHD mice grow in response to 5-day bGH. In contrast, both 0 day and 7-day-old mice are able to respond to a single GH pulse by phosphorylating hepatic Stat5. This suggests that hepatic GHR signaling takes place from birth, but that this GHR activation does not result in growth acceleration or increased IGF1 production. The presence of hepatic pY-Stat5 in mice that have high GH-concentrations suggests that hepatic Stat5 phosphorylation follows an endogenous GH pulse as in older mice.