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The Dual Effector Theory

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Abstract

The sections in this article are:

1 Studies Investigating the Validity of the Dual Effector Theory
1.1 Differences Between Growth Hormone and Insulin‐like Growth Factor I Actions In Vivo in Animals
1.2 Differences in Effects of Growth Hormone and Insulin‐like Growth Factor I In Vivo in Humans
1.3 Localization of Growth Hormone Receptors: Indirect Evidence for a Local Effect of Growth Hormone
1.4 Local Action of Growth Hormone on Tissues
1.5 Effects of Growth Hormone and Insulin‐like Growth Factor I on Cells of Different Maturation
1.6 Evidence In Vivo for a Stimulatory Effect of Growth Hormone, but not of Insulin‐like Growth Factor I, on Progenitor Cells in the Growth Plate
2 Conclusion and Discussion
3 Modified Dual Effector Theory of Growth Hormone and Insulin‐Like Growth Factor I Action in the Growth Plate
Figure 1. Figure 1.

Effects of local administration of growth hormone (GH) on longitudinal bone growth. In hypophysectomized male rats, GH was injected into the proximal growth plate of the right tibia. The contralateral leg received the same volume of saline. The two bars to the right represent rats that received saline in both the left and the right proximal growth plates of the tibia. Longitudinal bone growth was measured by the tetracycline method.

From Isaksson et al. with permission
Figure 2. Figure 2.

The dual effector theory as originally proposed by Green et al. in 1985 .

From Green with permission
Figure 3. Figure 3.

Hypothetical model for the stimulatory effect of growth hormone (GH) on longitudinal bone growth based on the original dual effector theory introduced by Green et al. . IGF‐I, insulin‐like growth factor I.

From Isaksson et al. with permission
Figure 4. Figure 4.

Effects of local administration of growth hormone (GH) on insulin‐like growth factor I (IGF‐I)‐immunoreactive cells in the tibial epiphyseal growth plate of hypophysectomized rats. The GH was injected daily for 5 days through a cannula implanted in the epiphysis of the right tibia. The left leg was injected with the same volume of saline. Rats were killed 18 h after the last injection. Sagittal sections of the epiphyseal growth plate of the proximal tibia were prepared and analyzed immunohistochemically for IGF‐I. A: Right leg treated with GH. B: Saline‐treated left leg. Note the difference in growth plate width and immunofluorescence of chondrocytes between the two photographs. Scale bar is 100 μm. Vertical arrow indicates width of the epiphyseal growth plate.

From Nilsson et al. with permission
Figure 5. Figure 5.

Effects of growth hormone (GH) and insulin‐like growth factor I (IGF‐I) on the percentage of label‐retaining cells compared to control in the germinal layer of the epiphyseal growth plate of hypophysectomized rats prelabeled with [3H]thymidine for 14 days, followed by a 14‐day washout period. In the germinal cell layer, GH increased the number of labeled cells compared to that in the control leg, whereas IGF‐I showed no stimulatory effect.

From Ohlsson et al. with permission
Figure 6. Figure 6.

Proposed mechanisms of action for growth hormone (GH) and insulin‐like growth factor I (IGF‐I) in stimulating growth of peripheral tissues and liver.

Figure 7. Figure 7.

A modified dual effector theory proposed by the authors for the mechanisms of action for growth hormone (GH) and insulin‐like growth factor I (IGF‐I) in stimulating longitudinal bone growth. Compare with the theory proposed earlier by the authors, which is shown in Figure .



Figure 1.

Effects of local administration of growth hormone (GH) on longitudinal bone growth. In hypophysectomized male rats, GH was injected into the proximal growth plate of the right tibia. The contralateral leg received the same volume of saline. The two bars to the right represent rats that received saline in both the left and the right proximal growth plates of the tibia. Longitudinal bone growth was measured by the tetracycline method.

From Isaksson et al. with permission


Figure 2.

The dual effector theory as originally proposed by Green et al. in 1985 .

From Green with permission


Figure 3.

Hypothetical model for the stimulatory effect of growth hormone (GH) on longitudinal bone growth based on the original dual effector theory introduced by Green et al. . IGF‐I, insulin‐like growth factor I.

From Isaksson et al. with permission


Figure 4.

Effects of local administration of growth hormone (GH) on insulin‐like growth factor I (IGF‐I)‐immunoreactive cells in the tibial epiphyseal growth plate of hypophysectomized rats. The GH was injected daily for 5 days through a cannula implanted in the epiphysis of the right tibia. The left leg was injected with the same volume of saline. Rats were killed 18 h after the last injection. Sagittal sections of the epiphyseal growth plate of the proximal tibia were prepared and analyzed immunohistochemically for IGF‐I. A: Right leg treated with GH. B: Saline‐treated left leg. Note the difference in growth plate width and immunofluorescence of chondrocytes between the two photographs. Scale bar is 100 μm. Vertical arrow indicates width of the epiphyseal growth plate.

From Nilsson et al. with permission


Figure 5.

Effects of growth hormone (GH) and insulin‐like growth factor I (IGF‐I) on the percentage of label‐retaining cells compared to control in the germinal layer of the epiphyseal growth plate of hypophysectomized rats prelabeled with [3H]thymidine for 14 days, followed by a 14‐day washout period. In the germinal cell layer, GH increased the number of labeled cells compared to that in the control leg, whereas IGF‐I showed no stimulatory effect.

From Ohlsson et al. with permission


Figure 6.

Proposed mechanisms of action for growth hormone (GH) and insulin‐like growth factor I (IGF‐I) in stimulating growth of peripheral tissues and liver.



Figure 7.

A modified dual effector theory proposed by the authors for the mechanisms of action for growth hormone (GH) and insulin‐like growth factor I (IGF‐I) in stimulating longitudinal bone growth. Compare with the theory proposed earlier by the authors, which is shown in Figure .

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Claes Ohlsson, Anders Lindahl, Jörgen Isgaard, Anders Nilsson, Olle G. P. Isaksson. The Dual Effector Theory. Compr Physiol 2011, Supplement 24: Handbook of Physiology, The Endocrine System, Hormonal Control of Growth: 501-514. First published in print 1999. doi: 10.1002/cphy.cp070516