We thank Bartke and Kopchick (1) for their interest in our study (2) and the important comment that elevated IGF-1 serum concentrations in mice with a conditional inactivation of the IGF-1 receptor in adipose tissue (IGF-1RaP2Cre mice) might be due to elevated growth hormone secretion despite the reported unaltered growth hormone levels in IGF-1RaP2Cre mice at the age of 24 weeks. Indeed, we did not find significantly higher growth hormone serum concentrations in 20 (10 males and 10 females) IGF-1RaP2Cre mice compared with 20 (10 males and 10 females) control mice at the age of 24 weeks.
In addition, in 12-week-old male and female IGF-1RaP2Cre and wild-type mice (20 mice per genotype), growth hormone serum concentrations were indistinguishable between the genotypes (means ± SD 12.4 ± 5.7 ng/ml in IGF-1RaP2Cre mice vs. 11.8 ± 4.9 ng/ml in control mice; P = 0.72). All growth hormone serum concentrations were measured in fed mice at 8:00 a.m. We agree that the ∼50% SD in circulating growth hormone might reflect the pulsatile pattern of growth hormone release.
In addition, we have generated mice lacking the IGF-1 receptor in the central nervous system through the use of synapsinCre mice (L. Koch, J.C.B., unpublished data). These mice do not exhibit the increase in body weight observed in IGF-1RaP2Cre mice, further supporting the notion that central dysregulation of IGF-1 receptor-signaling does not cause the observed phenotype of the IGF-1RaP2Cre mice.
Taken together, we appreciate the thoughtful comments by Bartke and Kopchick, which will certainly nurture further investigations on the regulation of growth hormone secretion in the IGF-1RaP2Cre mice. However, at this point, our experiments support an important role for IGF-1 action in adipocytes.
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