A direct growth effect of growth hormone in rat hindlimb shown by arterial infusion

Schlechter, Nicole; Russell, Sharon M.; Greenberg, S D; Spencer, E. Martin; Nicoll, Charles S.

doi:10.1152/ajpendo.1986.250.3.e231

Cited by 54 publications

(43 citation statements)

References 16 publications

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“…Husbandry conditions and anesthetics used were as described (43). Some of the rats were made diabetic by giving them an intrajugular injection of streptozotocin (65 mg per kg of body weight) on each of 2 consecutive days to destroy the beta cells of the pancreatic islets (44).…”

Section: Methodsmentioning

confidence: 99%

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Insulin exerts metabolic and growth-promoting effects by a direct action on the liver in vivo: clarification of the functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver.

Griffen

Russell

Katz

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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The functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver has not been established. Previous studies indicated that insulin does not acutely regulate glucose metabolism by a direct hepatic effect. More recent observations suggest that the role of insulin in regulating body growth may be mediated, at least in part, by the liver. Our experiments were designed to test whether insulin can promote body growth and regulate glucose metabolism by a direct hepatic action in vivo. Rats were made diabetic by injections of streptozotocin, and insulin or solvent was infused into the jugular vein (JV) or the hepatic portal vein (HPV) for 14 days using catheters that were attached to osmotic minipumps. Infusion of a low dose of insulin (2 units per kg per day) into the JV had no effects on the hyperglycemia, body weight gain, tail growth, tibial epiphysial cartilage plate thickness, or serum levels of somatomedin C in the diabetic rats. However, the same dose given into the HPV caused a 30% reduction of blood glucose and stimulated a significant degree of growth, as determined by all indices. Infusion of a higher dose of insulin (5 units per kg per day) into either vein caused full restoration of body weight gain and tail growth and it restored the glycemic status almost to normal. However, it did not increase the tibial epiphysial plate width or serum somatomedin C levels above those of the rats given the low dose of the hormone into the HPV. These results indicate that insulin can act directly on the liver to promote body growth and to regulate glucose metabolism. The significance of direct delivery of insulin from the pancreatic beta cells to the liver may be as much for growth control as for glucose homeostasis.

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Section: Methodsmentioning

confidence: 99%

“…Details of the procedures used to construct the catheters and to attach them to the osmotic minipumps were described (43). The methods used by Mick and Nicoll (47) to catheterize the jugular vein (JV) and the HPV of pigeons were modified for use in the rat.…”

Section: Methodsmentioning

confidence: 99%

Insulin exerts metabolic and growth-promoting effects by a direct action on the liver in vivo: clarification of the functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver.

Griffen

Russell

Katz

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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“…Although most of the early evidence in support of this theory was derived from in vitro work, Schoenle et al (5) recently demonstrated a dose-related growth-promoting effect of systemically infused human somatomedin (hSm) on the proximal tibial epiphyseal plate of hypophysectomized rats. However, a local effect of GH on tibial cartilage growth has also been demonstrated in hypophysectomized rats in vivo by direct injection into the proximal tibial epiphyseal plate (6,7), by intraarticular injection into the knee joint or administration into the epiphysis by implanted cannula (8), and by chronic infusion into the arterial supply of one hindlimb (9). In addition, numerous cells and tissues have been shown to produce somatomedins in vitro, either spontaneously or in response to GH (10)(11)(12)(13)(14)(15)(16)(17)(18).…”

mentioning

confidence: 99%

“…To investigate this possibility we used the system of Schlechter et al (9), which permits chronic infusion into the arterial supply of one hindlimb of a rat. With this procedure, we have demonstrated a direct growth-promoting effect of human somatomedin C (hSm-C) on the proximal tibial epiphyseal plate of hypophysectomized rats.…”

mentioning

confidence: 99%

Evidence suggesting that the direct growth-promoting effect of growth hormone on cartilage in vivo is mediated by local production of somatomedin.

Schlechter¹,

Russell²,

Spencer³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

291

125

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We have used a catheterization system that permits chronic infusion into the arterial supply of one hindlimb of rats to study the direct effects of rat growth hormone and human somatomedin C on growth of the tibial epiphyseal cartilage plate in hypophysectomized rats. Rat growth hormone (0.4 ,.g per day) or human somatomedin C (0.25, 1, or 4 ,ug per day) stimulated growth of the epiphyseal plate of the infused limb but not of that of the contralateral noninfused limb. The somatomedin C had a dose-related effect. Rabbit antiserum to human somatomedin C, but not normal rabbit serum, completely abolished the direct growth effect of the rat growth hormone when it was co-infused with the hormone. These results support the concept that growth hormone stimulates long bone growth by inducing local production of somatomedin, which in turn stimulates cell proliferation in an autocrine or paracrine fashion. However, they do not exclude the possibility that serum somatomedin may also play a role.The somatomedin hypothesis of Salmon and Daughaday (1) maintains that the growth-promoting actions of growth hormone (GH) are indirect and act via GH-dependent plasma factors named somatomedins or insulin-like growth factors. This hypothesis has evolved to include the concept that somatomedins are produced primarily by the liver in response to GH (2-4). Although most of the early evidence in support of this theory was derived from in vitro work, Schoenle et al. (5) recently demonstrated a dose-related growth-promoting effect of systemically infused human somatomedin (hSm) on the proximal tibial epiphyseal plate of hypophysectomized rats. However, a local effect of GH on tibial cartilage growth has also been demonstrated in hypophysectomized rats in vivo by direct injection into the proximal tibial epiphyseal plate (6, 7), by intraarticular injection into the knee joint or administration into the epiphysis by implanted cannula (8), and by chronic infusion into the arterial supply of one hindlimb (9). In addition, numerous cells and tissues have been shown to produce somatomedins in vitro, either spontaneously or in response to GH (10-18). Thus, it is possible that GH exerts its direct effects by stimulating local production of somatomedins.To investigate this possibility we used the system of Schlechter et al. (9), which permits chronic infusion into the arterial supply of one hindlimb of a rat. With this procedure, we have demonstrated a direct growth-promoting effect of human somatomedin C (hSm-C) on the proximal tibial epiphyseal plate of hypophysectomized rats. In addition, we have found that the local effect of rat GH (rGH) could be completely abolished by co-infusing an antiserum raised against hSm-C. MATERIALS AND METHODSMale Long-Evans rats (125-150 g) were obtained from our breeding colony. Husbandry conditions were as described (9). The animals were hypophysectomized by the transauricular approach (19) 14 days prior to catheterization. On the day of catheterization, they were reanesthetized (9) and the right superi...

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“…Growth hormone increases longitudinal bone growth by stimulating cell differentiation in the germinal zone of the growth plate (Isaksson et al 1982, Schlechter et al 1986, Nilsson et al 1987, Isaksson et al 1988. Callus formation in healing diaphyseal fractures shows many similarities with the bone formation of the growth plate (Mindell et al 1971, Page et al 1986).…”

mentioning

confidence: 99%

Growth hormone promotes healing of tibial fractures in the rat

Nielsen¹,

Bak²,

Jørgensen³

et al. 1991

Acta Orthopaedica Scandinavica

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A direct growth effect of growth hormone in rat hindlimb shown by arterial infusion

Cited by 54 publications

References 16 publications

Insulin exerts metabolic and growth-promoting effects by a direct action on the liver in vivo: clarification of the functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver.

Insulin exerts metabolic and growth-promoting effects by a direct action on the liver in vivo: clarification of the functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver.

Evidence suggesting that the direct growth-promoting effect of growth hormone on cartilage in vivo is mediated by local production of somatomedin.

Growth hormone promotes healing of tibial fractures in the rat

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