The insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs), which regulate IGF activity, play a fundamental role in renal cell proliferation and differentiation. The thyroid hormone is considered to be required for kidney development; excess induces local hypertrophy and hyperplasia. The aim of the present study was to investigate the possible involvement of the IGF/IGFBP system in thyroid hormone-induced renal growth during the development of the rat. Our results show that thyroid hormone withdrawal by 6-propyl-2-thiouracil (PTU)-treatment of rats at all ages had no effect on renal IGFBP-4 mRNA levels, whereas the abundance of the serum protein was decreased compared to controls. Intraperitoneal triiodothyronine (T3) administration to hypothyroid rats resulted in renal hypertrophy associated with a significant upregulation of IGFBP-4 expression with increased levels of renal IGFBP-4 mRNA and serum protein. T3-induced upregulation of IGFBP-4 expression suggests the involvement of the local IGF/IGFBP system in T3-induced renal hypertrophy.
Key words:
Triiodothyronine - IGFBP-4 - Kidney Hypertrophy
References
-
1
Froesch E R, Schmid C, Schwander J, Zapf J.
Actions of insulin-like growth factors.
Annual Review of Physiology.
1985;
47
443-467
-
2
Rechler M M.
Insulin-like growth factor binding proteins.
Vitamins and Hormones.
1993;
47
1-114
-
3
Ferry R J Jr, Katz L E, Grimberg A, Cohen P, Weinzimer S A.
Cellular actions of insulin-like growth factor binding proteins.
Hormone and Metabolic Research.
1999;
31
192-202
-
4
Jones J I, Clemmons D R.
Insulin-like growth factors and their binding proteins: biological actions.
Endocrine Reviews.
1995;
16
3-34
-
5
Daughaday W H, Rotwein P.
Insulin-like growth factor I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations.
Endocrine Reviews.
1989;
10
68-91
-
6
Rosenfeld R G, Lamson G, Pham H, Oh Y, Conover C, De Leon D D, Donovan S M, Ocrant I, Giudice L.
Insulin-like growth factor binding proteins.
Recent Progress in Hormone Research.
1990;
46
99-163
-
7
Shapiro L E, Samuels H H.
Yaffe BM. Thyroid and glucocorticoid hormones synergistically control growth hormone mRNA in cultured GH1 cells.
Proceedings of the National Academy of Sciences of the USA.
1978;
75
45-49
-
8
Samuels M H, Wierman M E, Wang C, Ridgway E C.
The effect of alterated thyroid status on pituitary hormone messenger ribonucleic acid concentrations in the rat.
Endocrinology.
1989;
124
2277-2282
-
9
Hochberg Z, Bick T, Harel Z.
Alterations of human growth hormone binding by rat liver membranes during hypo- and hyperthyroidism.
Endocrinology.
1990;
126
325-329
-
10
Gallo G, de Marchis M, Voci A, Fugassa E.
Expression of hepatic mRNAs for insulin-like growth factors-I and -II during the development of hypothyroid rats.
Journal of Endocrinology.
1991;
131
367-372
-
11
Nanto-Salonen K, Rosenfeld R G.
Insulin-like growth factor binding protein expression in the hypothyroid rat is age dependent.
Endocrinology.
1992;
131
1489-1496
-
12
Frystyk J, Gronbaek H.
Skjaerbaek C, Flyvbjerg A. Effect of hypothyroidism on circulating levels of free and total IGF-I and IGFBPs in rats.
American Journal of Physiology.
1995;
269
E840-E845
-
13
Demori I, Bottazzi C, Voci A, Gallo G, Scharf J G, Fugassa E.
Triiodothyronine increases insulin-like growth factor protein-4 expression in rat hepatocytes.
Journal of Endocrinology.
1997;
154
155-165
-
14
Demori I, Bottazzi C, Fugassa E.
Tri-iodothyronine increases insulin-like growth factor protein-2 expression in cultured hepatocytes from hypothyroid rats.
Journal of Endocrinology.
1999;
161
465-474
-
15
Feld S, Hirschberg R.
Growth Hormone, the Insulin-like growth factor system, and the kidney.
Endocrine Reviews.
1996;
17
423-480
-
16
Flyvbjerg A, Kessler U, Dorka B, Funk B, Orskov H, Kiess W.
Transient increase in renal insulin-like growth factor binding proteins during initial kidney hypertrophy in experimental diabetes in rats.
Diabetologia.
1992;
35
589-593
-
17
Bradley S E, Stephan F, Coelho J B, Reville P.
The thyroid and the kidney.
Kidney International.
1974;
6
346-365
-
18
Chan Y L, Gutell R, Noller H F, Wool I G.
The nucleotide sequence of a rat 18S ribosomal ribonucleic acid gene and a proposal for the secondary structure of 18S ribosomal ribonucleic acid.
Journal of Biological Chemistry.
1984;
259
224-230
-
19
Hossenlopp P, Seurin D, Segovia-Quinson B, Hardouin S, Binoux M.
Analysis of serum insulin-like growth factor binding proteins using Western blotting: use of the method for tritation of the binding proteins and competitive binding studies.
Analytical Biochemistry.
1986;
154
138-143
-
20
Chomczynski P, Sacchi N.
Single-step method of RNA isolation by acid guanidinium thyocyanate-phenol-chloroform extraction.
Analytical Biochemistry.
1987;
162
156-159
-
21 Werner W, Ingbars I. The thyroid. In: Braverman LE, Utiger RD (eds). Philadelphia:; Lippincott-Raven Publishers, 1996 7th ed: 628-631
-
22
Donovan S M, Oh Y, Priam H, Rosenfeld R G.
Ontogeny of serum insulin-like growth factor binding proteins in the rat.
Endocrinology.
1989;
125
2621-2627
-
23
Ali M, Rougon-Rapuzzi G, Clos J.
Response of hypothalamo-neurohypophyseal axis (AVP system) and the kidney to salt load in young propylthiouracil-treated rats.
Hormone and Metabolic Research.
1985;
17
502-506
-
24
Flyvbjerg A, Bornfeldt K E, Marshall S M, Arnqvist H J, Orskov H.
Kidney IGF-I mRNA in initial renal hypertrophy in experimental diabetes in rats.
Diabetologia.
1990;
33
334-338
-
25
Gronboek H.
Nielsen B. Flyvbjerg A, Orskov H. Effect of graded renal ablation on kidney and serum insulin-like growth factor-I (IGF-I) and IGF binding proteins in rats: relation to compensatory renal growth.
Metabolism.
1997;
46
29-35
-
26
Koldovsky O.
Hormones in milk.
Life Sciences.
1980;
26
1833-1836
-
27
Miyatake N, Shikata K, Wada J, Sugimoto H, Takahashi S I, Makino H.
Differential distribution of insulin-like growth factor-I and insulin-like growth factor binding proteins in experimental diabetic rat kidney.
Nephron.
1999;
81
317-323
-
28
Demori I, Balocco S, Voci A, Fugassa E.
Increased insulin-like growth factor binding protein-4 expression after partial hepatectomy in the rat.
American Journal of Physiology.
2000;
278
G384-G389
-
29
La Tour D, Mohan S, Linkhart T A, Baylink D J, Strong D D.
Inibitory insulin-like growth factor-binding protein: cloning, complete sequence and physiological regulation.
Molecular Endocrinology.
1990;
4
1806-1814
-
30
Schneider M R, Lahm H, Wu M, Hoeflich A, Wolf E.
Transgenic mouse models for studying the functions of insulin-like growth factor-binding proteins.
Faseb Journal.
2000;
14
629-640
-
31
Miyakoshi N, Richman C, Qin X, Baylink D J, Mohan S.
Effects of recombinant insulin-like growth factor-binding protein-4 on bone formation parameters in mice.
Endocrinology.
1999;
140
5719-5728
-
32
Rees C, Clemmons D R, Horvitz G D, Clarke J B, Busby W H.
A protease-resistant form of insulin-like growth factor (IGF) binding protein-4 inhibits IGF-I actions.
Endocrinology.
1998;
139
4182-4188
-
33
Fowlkers J, Freemark M.
Evidence for a novel insulin-like growth factor (IGF)-dependent protease regulating IGF-binding protein-4 in dermal fibroblasts.
Endocrinology.
1992;
131
2071-2076
-
34
Irwin J C, Dsupin B A, Giudice L C.
Regulation of insulin-like growth factor binding protein-4 in human endometrial stromal cell cultures: evidence for ligand-induced proteolysis.
Journal of Clinical Endocrinology and Metabolism.
1995;
80
619-626
-
35
Singh P, Dai B, Dhruva B, Widen S G.
Episomal expression of sense and antisense insulin-like growth factor (IGF) binding protein-4 complementary DNA alters the mitogenic response of a human colon cancer cell line (HT-29) by mechanisms that are independent of and dependent upon IGF-I.
Cancer Research.
1994;
54
6563-6570
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