Role of GH and IGF-I in the regulation of IGF-I, IGF-I receptor and IGF binding protein gene expression in the rat spleen

Horacio M. Domené, Rina Meidan, Shoshana Yakar, Zila Shen-Orr, Fernando Cassorla, Charles T. Roberts, Derek LeRoith

Research output: Contribution to journalArticle

Abstract

To characterize the expression of the IGF-I system in the spleen and its role in spleen growth, we have studied the effect of hypophysectomy and the action of either GH or IGF-I treatment on the expression of several components of the IGF system in the rat. Female Sprague-Dawley rats were hypophysectomized (Hx) on postnatal day 50, and five animals each received twice-daily sc injections of saline, bovine GH (bGH; 84 μg/animal/day), or recombinant human IGF-I (rhIGF-I; 125 μg/animal/day) for 11 days. Compared to sham-operated controls, Hx animals exhibited a reduction in both body (192.6 ± 5.6 g (mean ± S.E.M.) vs. 268.6 ± 6.0 g; P<0.001) and spleen weights (0.42 ± 0.03 g vs. 0.84 ± 0.06 g; P<0.001). The reduction in body and spleen weights in Hx animals was partially prevented by both bGH and rhIGF-I. Body weights were 234.2 ± 5.3 g (P<0.001) after bGH and 213.8 ± 6.3 g (P<0.05) after rhIGF-I. Spleen weights were 0.56 ± 0.048 after bGH P<0.01 and 0.53 ± 0.05 g after rhIGF-I (P<0.05). Serum GH and IGF-I levels were markedly reduced in Hx animals and bGH partially maintained IGF-I levels. Hypophysectomy reduced spleen IGF-I mRNA levels (30.6 ± 7.5% of control values; P<0.05) and this reduction was prevented by bGH (96.6 ± 24.2%; NS) but not by rhIGF-I (39.9 ± 5.0% NS vs. Hx). There were no changes in GH receptor or IGF-I receptor mRNA levels in Hx or bGH or rhIGF-I-treated animals. When IGF-I binding protein (IGFBP) mRNA levels were studied under these conditions, we found that IGFBP-1 mRNA was not detected in spleen; IGFBP-2 mRNA levels were reduced in Hx rats (67.9 ± 7.4% of control values, P<0.05) and bGH treatment prevented this reduction (95.5 ± 12.2%, NS). IGFBP-3 mRNA levels were not affected by hypophysectomy or by bGH treatment, but were reduced in rhIGF-treated rats (69.6 ± 3.0%, P<0.05). On the other hand, IGFBP-4 mRNA levels were increased in Hx rats (136.4 ± 15.9% of control values, P<0.05) and bGH treatment prevented this increase. These data demonstrate that several components of the IGF system are expressed in rat spleen and that following hypophysectomy, there is a reduction in spleen weight that correlates with a reduction in local IGF-I gene expression and, presumably, a reduction in IGF-I bioavailability due to a decrease in IGFBP-2 and an increase in IGFBP-4 gene expression.

Original languageEnglish (US)
Pages (from-to)215-226
Number of pages12
JournalRegulatory Peptides
Volume52
Issue number3
DOIs
StatePublished - Aug 4 1994

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Insulin-Like Growth Factor Binding Proteins
IGF Type 1 Receptor
Insulin-Like Growth Factor I
Gene expression
Rats
Spleen
Gene Expression
Carrier Proteins
Animals
Hypophysectomy
Messenger RNA
Insulin-Like Growth Factor Binding Protein 4
Insulin-Like Growth Factor Binding Protein 2
Weights and Measures
Body Weight
Insulin-Like Growth Factor Binding Protein 1
Insulin-Like Growth Factor Binding Protein 3

Keywords

  • Gene expression
  • Insulin-like growth factor
  • Insulin-like growth factor binding protein
  • mRNA level
  • Splenic growth

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

Cite this

Role of GH and IGF-I in the regulation of IGF-I, IGF-I receptor and IGF binding protein gene expression in the rat spleen. / Domené, Horacio M.; Meidan, Rina; Yakar, Shoshana; Shen-Orr, Zila; Cassorla, Fernando; Roberts, Charles T.; LeRoith, Derek.

In: Regulatory Peptides, Vol. 52, No. 3, 04.08.1994, p. 215-226.

Research output: Contribution to journalArticle

Domené, Horacio M. ; Meidan, Rina ; Yakar, Shoshana ; Shen-Orr, Zila ; Cassorla, Fernando ; Roberts, Charles T. ; LeRoith, Derek. / Role of GH and IGF-I in the regulation of IGF-I, IGF-I receptor and IGF binding protein gene expression in the rat spleen. In: Regulatory Peptides. 1994 ; Vol. 52, No. 3. pp. 215-226.
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abstract = "To characterize the expression of the IGF-I system in the spleen and its role in spleen growth, we have studied the effect of hypophysectomy and the action of either GH or IGF-I treatment on the expression of several components of the IGF system in the rat. Female Sprague-Dawley rats were hypophysectomized (Hx) on postnatal day 50, and five animals each received twice-daily sc injections of saline, bovine GH (bGH; 84 μg/animal/day), or recombinant human IGF-I (rhIGF-I; 125 μg/animal/day) for 11 days. Compared to sham-operated controls, Hx animals exhibited a reduction in both body (192.6 ± 5.6 g (mean ± S.E.M.) vs. 268.6 ± 6.0 g; P<0.001) and spleen weights (0.42 ± 0.03 g vs. 0.84 ± 0.06 g; P<0.001). The reduction in body and spleen weights in Hx animals was partially prevented by both bGH and rhIGF-I. Body weights were 234.2 ± 5.3 g (P<0.001) after bGH and 213.8 ± 6.3 g (P<0.05) after rhIGF-I. Spleen weights were 0.56 ± 0.048 after bGH P<0.01 and 0.53 ± 0.05 g after rhIGF-I (P<0.05). Serum GH and IGF-I levels were markedly reduced in Hx animals and bGH partially maintained IGF-I levels. Hypophysectomy reduced spleen IGF-I mRNA levels (30.6 ± 7.5{\%} of control values; P<0.05) and this reduction was prevented by bGH (96.6 ± 24.2{\%}; NS) but not by rhIGF-I (39.9 ± 5.0{\%} NS vs. Hx). There were no changes in GH receptor or IGF-I receptor mRNA levels in Hx or bGH or rhIGF-I-treated animals. When IGF-I binding protein (IGFBP) mRNA levels were studied under these conditions, we found that IGFBP-1 mRNA was not detected in spleen; IGFBP-2 mRNA levels were reduced in Hx rats (67.9 ± 7.4{\%} of control values, P<0.05) and bGH treatment prevented this reduction (95.5 ± 12.2{\%}, NS). IGFBP-3 mRNA levels were not affected by hypophysectomy or by bGH treatment, but were reduced in rhIGF-treated rats (69.6 ± 3.0{\%}, P<0.05). On the other hand, IGFBP-4 mRNA levels were increased in Hx rats (136.4 ± 15.9{\%} of control values, P<0.05) and bGH treatment prevented this increase. These data demonstrate that several components of the IGF system are expressed in rat spleen and that following hypophysectomy, there is a reduction in spleen weight that correlates with a reduction in local IGF-I gene expression and, presumably, a reduction in IGF-I bioavailability due to a decrease in IGFBP-2 and an increase in IGFBP-4 gene expression.",
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T1 - Role of GH and IGF-I in the regulation of IGF-I, IGF-I receptor and IGF binding protein gene expression in the rat spleen

AU - Domené, Horacio M.

AU - Meidan, Rina

AU - Yakar, Shoshana

AU - Shen-Orr, Zila

AU - Cassorla, Fernando

AU - Roberts, Charles T.

AU - LeRoith, Derek

PY - 1994/8/4

Y1 - 1994/8/4

N2 - To characterize the expression of the IGF-I system in the spleen and its role in spleen growth, we have studied the effect of hypophysectomy and the action of either GH or IGF-I treatment on the expression of several components of the IGF system in the rat. Female Sprague-Dawley rats were hypophysectomized (Hx) on postnatal day 50, and five animals each received twice-daily sc injections of saline, bovine GH (bGH; 84 μg/animal/day), or recombinant human IGF-I (rhIGF-I; 125 μg/animal/day) for 11 days. Compared to sham-operated controls, Hx animals exhibited a reduction in both body (192.6 ± 5.6 g (mean ± S.E.M.) vs. 268.6 ± 6.0 g; P<0.001) and spleen weights (0.42 ± 0.03 g vs. 0.84 ± 0.06 g; P<0.001). The reduction in body and spleen weights in Hx animals was partially prevented by both bGH and rhIGF-I. Body weights were 234.2 ± 5.3 g (P<0.001) after bGH and 213.8 ± 6.3 g (P<0.05) after rhIGF-I. Spleen weights were 0.56 ± 0.048 after bGH P<0.01 and 0.53 ± 0.05 g after rhIGF-I (P<0.05). Serum GH and IGF-I levels were markedly reduced in Hx animals and bGH partially maintained IGF-I levels. Hypophysectomy reduced spleen IGF-I mRNA levels (30.6 ± 7.5% of control values; P<0.05) and this reduction was prevented by bGH (96.6 ± 24.2%; NS) but not by rhIGF-I (39.9 ± 5.0% NS vs. Hx). There were no changes in GH receptor or IGF-I receptor mRNA levels in Hx or bGH or rhIGF-I-treated animals. When IGF-I binding protein (IGFBP) mRNA levels were studied under these conditions, we found that IGFBP-1 mRNA was not detected in spleen; IGFBP-2 mRNA levels were reduced in Hx rats (67.9 ± 7.4% of control values, P<0.05) and bGH treatment prevented this reduction (95.5 ± 12.2%, NS). IGFBP-3 mRNA levels were not affected by hypophysectomy or by bGH treatment, but were reduced in rhIGF-treated rats (69.6 ± 3.0%, P<0.05). On the other hand, IGFBP-4 mRNA levels were increased in Hx rats (136.4 ± 15.9% of control values, P<0.05) and bGH treatment prevented this increase. These data demonstrate that several components of the IGF system are expressed in rat spleen and that following hypophysectomy, there is a reduction in spleen weight that correlates with a reduction in local IGF-I gene expression and, presumably, a reduction in IGF-I bioavailability due to a decrease in IGFBP-2 and an increase in IGFBP-4 gene expression.

AB - To characterize the expression of the IGF-I system in the spleen and its role in spleen growth, we have studied the effect of hypophysectomy and the action of either GH or IGF-I treatment on the expression of several components of the IGF system in the rat. Female Sprague-Dawley rats were hypophysectomized (Hx) on postnatal day 50, and five animals each received twice-daily sc injections of saline, bovine GH (bGH; 84 μg/animal/day), or recombinant human IGF-I (rhIGF-I; 125 μg/animal/day) for 11 days. Compared to sham-operated controls, Hx animals exhibited a reduction in both body (192.6 ± 5.6 g (mean ± S.E.M.) vs. 268.6 ± 6.0 g; P<0.001) and spleen weights (0.42 ± 0.03 g vs. 0.84 ± 0.06 g; P<0.001). The reduction in body and spleen weights in Hx animals was partially prevented by both bGH and rhIGF-I. Body weights were 234.2 ± 5.3 g (P<0.001) after bGH and 213.8 ± 6.3 g (P<0.05) after rhIGF-I. Spleen weights were 0.56 ± 0.048 after bGH P<0.01 and 0.53 ± 0.05 g after rhIGF-I (P<0.05). Serum GH and IGF-I levels were markedly reduced in Hx animals and bGH partially maintained IGF-I levels. Hypophysectomy reduced spleen IGF-I mRNA levels (30.6 ± 7.5% of control values; P<0.05) and this reduction was prevented by bGH (96.6 ± 24.2%; NS) but not by rhIGF-I (39.9 ± 5.0% NS vs. Hx). There were no changes in GH receptor or IGF-I receptor mRNA levels in Hx or bGH or rhIGF-I-treated animals. When IGF-I binding protein (IGFBP) mRNA levels were studied under these conditions, we found that IGFBP-1 mRNA was not detected in spleen; IGFBP-2 mRNA levels were reduced in Hx rats (67.9 ± 7.4% of control values, P<0.05) and bGH treatment prevented this reduction (95.5 ± 12.2%, NS). IGFBP-3 mRNA levels were not affected by hypophysectomy or by bGH treatment, but were reduced in rhIGF-treated rats (69.6 ± 3.0%, P<0.05). On the other hand, IGFBP-4 mRNA levels were increased in Hx rats (136.4 ± 15.9% of control values, P<0.05) and bGH treatment prevented this increase. These data demonstrate that several components of the IGF system are expressed in rat spleen and that following hypophysectomy, there is a reduction in spleen weight that correlates with a reduction in local IGF-I gene expression and, presumably, a reduction in IGF-I bioavailability due to a decrease in IGFBP-2 and an increase in IGFBP-4 gene expression.

KW - Gene expression

KW - Insulin-like growth factor

KW - Insulin-like growth factor binding protein

KW - mRNA level

KW - Splenic growth

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