Intracerebral administration of insulin-like growth factor I decreases circulating growth hormone levels in the fetal pig

1991 ◽  
Vol 124 (5) ◽  
pp. 563-568 ◽  
Author(s):  
G. S. G. Spencer ◽  
A. A. Macdonald ◽  
H. L. Buttle ◽  
L. G. Moore ◽  
S. S. Carlyle

Abstract. Radioimmunoassayable IGF-I levels were measured in the cerebrospinal fluid and plasma of pig fetuses at 94 days gestational age. Mean plasma IGF-I levels were 128.5 ± 5.8 μg/l while the concentration in the cerebrospinal fluid was 25.8 ± 4.4 μg/l. The effect of intracerebroventricular administration of IGF-I on circulating GH levels was also studied in pig fetuses in utero. Eighteen pig fetuses were fitted with indwelling carotid artery and juglar vein catheters. Nine fetuses were given 1500 ng of pure IGF-I in 100 μl 0.9% saline by direct injection into a right lateral ventricle. Nine further fetuses (controls) were similarly given 100 μl of saline without IGF-I. GH levels in the control fetuses were ~200 μg/l and showed marked fluctuations with episodic intervals of about 40 min. By contrast, in the IGF-I-treated fetuses, GH levels were dramatically lowered by 20 min after IGF administration and remained low throughout the 4-h study. The episodic variations in GH were abolished and levels remained fairly constant at ca. 40 μg/l. From these results we surmise that the low levels of IGF-I in the fetus may contribute to their high GH levels. At this stage it is not possible to identify whether the IGF-I inhibition is a direct effect on the pituitary or is mediated by increased somatostatin, decreased GHRH or both.

1991 ◽  
Vol 124 (5) ◽  
pp. 602-607 ◽  
Author(s):  
Ben A. A. Scheven ◽  
Nicola J. Hamilton

Abstract. Longitudinal growth was studied using an in vitro model system of intact rat long bones. Metatarsal bones from 18- and 19-day-old rat fetuses, entirely (18 days) or mainly (19 days) composed of chondrocytes, showed a steady rate of growth and radiolabelled thymidine incorporation for at least 7 days in serum-free media. Addition of recombinant human insulin-like growth factor-I to the culture media resulted in a direct stimulation of the longitudinal growth. Recombinant human growth hormone was also able to stimulate bone growth, although this was generally accomplished after a time lag of more than 2 days. A monoclonal antibody to IGF-I abolished both the IGF-I and GH-stimulated growth. However, the antibody had no effect on the growth of the bone explants in control, serum-free medium. Unlike the fetal long bones, bones from 2-day-old neonatal rats were arrested in their growth after 1-2 days in vitro. The neonatal bones responded to IGF-I and GH in a similar fashion as the fetal bones. Thus in this study in vitro evidence of a direct effect of GH on long bone growth via stimulating local production of IGF by the growth plate chondrocytes is presented. Furthermore, endogenous growth factors, others than IGFs, appear to play a crucial role in the regulation of fetal long bone growth.


1994 ◽  
Vol 266 (5) ◽  
pp. E776-E785 ◽  
Author(s):  
P. A. Weller ◽  
M. J. Dauncey ◽  
P. C. Bates ◽  
J. M. Brameld ◽  
P. J. Buttery ◽  
...  

Regulation of insulin-like growth factor I (IGF-I) and growth hormone (GH) receptor mRNA in liver and muscle by energy status was assessed in 2-mo-old pigs by altering thermoregulatory demand and energy intake over a 5-wk period to produce a range of plasma IGF-I concentrations from 3.5 +/- 0.7 to 28.9 +/- 6.2 nmol/l. These values were related directly to growth rates (0.06 +/- 0.02 to 0.44 +/- 0.01 kg/day) and total hepatic IGF-I mRNA levels. Increased growth rates were accompanied by an increase in hepatic class 1 and class 2 IGF-I mRNA levels and an increase in the ratio of class 2 to class 1 IGF-I mRNA in liver, suggesting a distinct role for class 2 expression in the endocrine growth response. High levels of class 1 transcripts and a virtual absence of class 2 transcripts characterized all muscle tissues examined, and there was no correlation with plasma IGF-I levels. This suggests that growth promotion in response to increased energy status is regulated via endocrine hepatic IGF-I rather than via a paracrine response. The levels of GH receptor mRNA were positively correlated with overall growth rate (P < 0.005) in liver and negatively correlated (P < 0.05) in muscle, indicating distinct tissue-specific effects of energy status.


1999 ◽  
Vol 81 (2) ◽  
pp. 145-152 ◽  
Author(s):  
Myriam Sanchez-Gomez ◽  
Kjell Malmlöf ◽  
Wilson Mejia ◽  
Antonio Bermudez ◽  
Maria Teresa Ochoa ◽  
...  

The aim of the present study was to investigate the influence of dietary protein level on the protein anabolic effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I). Female growing rats were fed on either a high- or a low-protein diet with crude protein contents of 222 and 83 g/kg respectively. The diets contained the same amount of metabolizable energy (15·1 MJ/kg) and were given during a 14 d period. During the same time, three groups of rats (n 8) on each diet received subcutaneous infusions of either saline, recombinant human GH (rhGH) or recombinant human IGF-I (rhIGF-I). rhGH and rhIGF-I were given in doses of 360 and 500 μg/d respectively. The low-protein diet alone reduced significantly (P < 0·05) IGF-I concentrations in serum and in tissue taken from the gastrocnemius muscle as well as IGF-I mRNA from the same muscle. The responses to rhGH and rhIGF-I in terms of muscle IGF-I and its mRNA were variable. However, when rhIGF-I was infused into rats on the high-protein diet, significantly elevated levels of IGF-I in muscle tissues could be observed. This was associated with a significantly (P < 0·05) increased N balance, whereas rhGH significantly (P < 0·05) enhanced the N balance in rats on the low-protein diet. Thus, it can be concluded that the level of dietary protein ingested regulates not only the effect of IGF-I on whole-body N economy but also the regulation of IGF-I gene expression in muscles. The exact mechanism by which GH exerts its protein anabolic effect, however, remains to be elucidated.


1997 ◽  
Vol 82 (4) ◽  
pp. 1064-1070 ◽  
Author(s):  
Michael I. Lewis ◽  
Thomas J. Lorusso ◽  
Mario Fournier

Lewis, Michael I., Thomas J. LoRusso, and Mario Fournier.Effect of insulin-like growth factor I and/or growth hormone on diaphragm of malnourished adolescent rats. J. Appl. Physiol. 82(4): 1064–1070, 1997.—Young growing animals appear to have significantly reduced “nutritional reserve” to short periods of unstressed starvation compared with adults, with resultant growth arrest and/or atrophy of diaphragm (Dia) muscle fibers. The aim of this study was to assess in an adolescent rat model of acute nutritional deprivation (ND; 72 h) the impact of insulin-like growth factor I (IGF-I), with or without added growth hormone (GH), on the cross-sectional areas (CSA) of individual Dia muscle fibers. Five groups were studied: 1) control (Ctr); 2) ND; 3) ND given IGF-I (ND/IGF-I); 4) ND given GH (ND/GH); and 5) ND given a combination of IGF-I and GH (ND/IGF-I/GH). IGF-I was given by a subcutaneously implanted osmotic minipump (200 μg/day), whereas GH was administered twice daily by a subcutaneous injection (250 μg every 12 h). Isometric contractile and fatigue properties of the Dia were determined in vitro. Forces were normalized for muscle CSA (i.e., specific force). Dia fiber type proportions were determined histochemically, and fiber CSA was quantified by using a computer-based image-processing system. Total serum IGF-I concentrations were significantly reduced in ND and ND/GH animals, compared with Ctr, and elevated in the groups receiving IGF-I. The provision of growth factors did not alter the contractile or fatigue properties of ND animals. Dia fiber type proportions were similar among the groups. In ND animals, there was a significant reduction in the CSA of types I, IIa, IIx, and IIc Dia fibers compared with Ctr. The administration of IGF-I alone or in combination with GH to ND animals significantly diminished the reduction in Dia fiber size. GH alone had no effect on Dia fiber size in ND animals. We conclude that with acute ND the peripheral resistance to the action of GH appears to be bypassed by the administration of IGF-I alone or in combination with GH.


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