Both rhGH and rhIGF-I are signaling molecules with the capacity to restore the rate of growth in certain subsets of slowly growing children. In some instances, heights attained at or near the time of cessation of linear growth are indistinguishable from the height distribution of the community as a whole or from the height distribution expected based on the heights of biological parents. The GH: IGF-I signaling system is sequential, forming a continuous loop wherein GH will stimulate production of IGF-I and IGF-I will inhibit production of GH. This feature suggests that a deficiency of GH will be accompanied by a deficiency of IGF-I and that treatment of GH deficiency with rhGH will restore IGF-I and the subnormal growth of combined GH: IGF-I deficiency. Although logical, this proposition is not always true. rhGH and rhIGF-I are distinct polypeptides, with distinct cell surface receptors and distinct intracellular signaling pathways both capable of amplifying distinct, yet overlapping, patterns of gene replication, protein synthesis and metabolic activities. These features suggest that neither treatment with rhGH nor rhIGF-I alone will invariably recapitulate the combined activities of the GH: IGF-I system, At the present time, this proposition appears both logical and true. The possibility that combined rhGH and rhIGF-I treatment can accomplish that which neither monotherapy can has been examined in gene knock-out experiments in animals and direct comparisons of GH, IGF-I and combined GH: IGF- treatments in animals and in children with short stature, normal GH and low IGF-I (primary IGF-I deficiency). In these experimental models, the growth rates with combined rhGH and rhIGF-I treatment exceed those of either monotherapy. The extent to which this proposition can be generalized to various short stature populations remains to be determined.

rhGH和rhIGF-1均是信号分子，具有在缓慢生长的儿童的某些亚群中恢复生长速率的能力。在某些情况下，在停止线性生长时或接近线性生长时达到的高度与整个群落的高度分布或基于生物学父母身高的预期高度分布没有区别。GH：IGF-1信号传导系统是连续的，形成一个连续的环，其中GH将刺激IGF-1的产生，而IGF-1将抑制GH的产生。该特征表明GH的缺乏将伴随IGF-I的缺乏，并且用rhGH治疗GH的缺乏将恢复IGF-1和复合GH的亚正常生长：IGF-1的缺乏。尽管是合乎逻辑的，但这种主张并不总是正确的。rhGH和rhIGF-1是截然不同的多肽，具有截然不同的细胞表面受体和截然不同的细胞内信号传导途径，均能够放大截然不同但又重叠的基因复制，蛋白质合成和代谢活性模式。这些特征表明，单独用rhGH或rhIGF-I进行治疗都不会不可避免地概括GH：IGF-I系统的联合活性。目前，这一主张既合乎逻辑又属实。在动物的基因敲除实验中以及在动物和儿童的GH，IGF-I和GH：IGF-I联合治疗的直接比较中，rhGH和rhIGF-I联合治疗可以完成单药治疗均无法完成的可能性。身材矮小，生长激素正常和低IGF-I（原发性IGF-I缺乏症）。在这些实验模型中，rhGH和rhIGF-I联合治疗的增长率超过了任何单一疗法的增长率。这个主张可以推广到各种身材矮小的人群的程度还有待确定。