After we learned that the old somatomedin hypothesis (that IGF-1 was the mediator between the GH and growth plate chondrocytes) was not completely correct and needed to be altered to account for the ability of GH to affect the chondrocytes directly, as well as the fact that besides the liver, IGF-1 seems to be produced in all types of organs and tissue, I wanted to focus on just how exactly IGF-1 helps the GH in longitudinal growth. It was shown that for lab rats that were genetically manipulated to be IGF-1 null, it was shown that the number of chondrocytes in the resting zone and the proliferation rate of the chondrocytes did not change that much.

This study I found seems to suggest that IGF-1 augments the effects of GH by acting only on the chondrocytes that are differentiating into the hypertrophy stage.

Study #1: Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy – JIE WANG, JIAN ZHOU and CAROLYN A. BONDY

Abstract

Longitudinal bone growth, and hence stature, are functions of growth plate chondrocyte proliferation and hypertrophy. Insulin-like growth factor 1 (Igf1) is reputed to augment longitudinal bone growth by stimulating growth plate chondrocyte proliferation. In this study, however, we demonstrate that chondrocyte numbers and proliferation are normal in Igf1 null mice despite a 35% reduction in the rate of long bone growth. Igf1 null hypertrophic chondrocytes differentiate normally in terms of expressing specialized proteins such as collagen X and alkaline phosphatase, but are smaller than wild-type at all levels of the hypertrophic zone. The terminal hypertrophic chondrocytes, which form the scaffold on which long bone growth extends, are reduced in linear dimension by 30% in Igf1 null mice, accounting for most of their decreased longitudinal growth. The expression of the insulin-sensitive glucose transporter, GLUT4, is significantly decreased and the insulin-regulated enzyme glycogen synthase kinase 3β (GSK3) is hypo-phosphorylated in Igf1 null chondrocytes. Glycogen levels were significantly decreased and ribosomal RNA levels were reduced by almost 75% in Igf1 null chondrocytes. These data suggest that Igf1 promotes longitudinal bone growth by ‘insulin-like’ anabolic actions which augment chondrocyte hypertrophy.

—Wang, J., Zhou, J., Bondy, C. A. Igf1 promotes longitudinal bone growth by insulin-like actions augmenting chondrocyte hypertrophy.

Analysis

This study is one of the most interesting studies I have found in a long time. This study shows that when it comes to modulation of the growth plate chondrocytes, the IGF-1 has an affect mainly on the process of differentiating into the hypertrophy stage. The most interesting is that the number of chondrocytes and the rate of proliferation does not seem to change for lab rodents which were born with the IGF1 gene deactivated.

This means that the IGF-1 has effects only on hypertrophy.

The effects of the having a deficient IGF-1 gene are the following…

1. a 35% reduction in the rate of long bone growth
2. have lower levels and rates of collagen type X and alkaline phosphatase release by the hypertrophic chondrocytes
3. the hypertrophic chondrocytes are reduced in linear dimension by 30%
4. expression of GLUT4 is significantly decreased
5. GSK3 is hypo-phosphorylated
6. Glycogen levels were significantly decreased
7. ribosomal RNA levels were reduced by almost 75%

If we look at the last 4 of the effects, they are all related to insulin like effects on the tissues. IGF-1 is very similar to Insulin in structure and function. This shows that its function for the growth plates is also from insulin similar anabolic actions which combines with the GH to get chondrocyte hypertrophy.

We see that at least for lab rats that while the bone length is not completely stunted, there is still a very substantial reduction, by as much as 35%. This could potentially turn a guy from 6 feet to 5 feet tall. The releasing of the specific proteins that are indicators of hypertrophic chondrocytes do occur but dramatically decreased.

This study reveals that it might be possible to modulate the growth rate of children through IGF-1 increase, while making sure that it does not reach levels that are too high resulting in disruptions to other types of metabolisms.