INSULIN-LIKE-GROWTH-FACTOR-II (IGF-II) IS MORE POTENT THAN IGF-I IN STIMULATING CORTISOL SECRETION FROM CULTURED BOVINE ADRENOCORTICAL-CELLS - INTERACTION WITH THE IGF-I RECEPTOR AND IGF-BINDING PROTEINS

被引:34
作者
WEBER, MM
SIMMLER, P
FOTTNER, C
ENGELHARDT, D
机构
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D O I
10.1210/en.136.9.3714
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Although the stimulating effect of insulin-like growth factor I (IGF-I) on adrenal steroidogenesis has been well established, the rob of IGF-II in the adult adrenal gland remains unknown. We, therefore, investigated the effect of recombinant human IGF-II on cortisol and cAMP synthesis from adult bovine adrenocortical cells. IGF-II, time and dose dependently, stimulated basal cortisol secretion maximally 3-fold. In combination with ACTH, IGF-IT (13 nM) synergistically increased cortisol secretion from 18-fold (10(-8) M ACTH) to 28-fold of untreated control levels. In contrast, IGF-I at equimolar concentrations did not show an effect on basal cortisol secretion, and in combination with ACTH elicited a significant weaker stimulatory effect than IGF-II (22-fold increase). The synergistic effect of IGF-II on ACTH-promoted cortisol secretion was paralleled by accumulation of cAMP in the culture medium. Although both IGF receptors are present in adult bovine adrenocortical cells, the effect of IGF-II seems to be mediated through interaction with the IGF-I receptor, as [Arg(54,55)]IGF-II, which only binds to the IGF-I receptor, was equipotent to native IGF-II, whereas [Leu(27)]IGF-II, which preferentially binds to the type II IGF receptor, did not show any effect. By Western ligand blotting, four different molecular forms of IGF-binding proteins (IGFBPs) were identified in conditioned medium of bovine adrenocortical cells with apparent molecular masses of 39-44, 34, 29, and 24 kilodaltons. ACTH treatment increased the abundance of all binding proteins, on the average, 2.3-fold, except for the 29-kDa band, which was predominantly induced 6.8-fold. Additionally, [des(1-3)]IGF-I, a truncated IGF variant that exhibits only minimal binding to IGFBPs, was significant more potent than IGF-I and elicited the same maximum stimulatory effect on cortisol secretion as IGF-II and [des(1-6)]IGF-II. In conclusion, these results demonstrate that 1) IGF-II stimulates basal as well as ACTH-induced cortisol secretion from bovine adrenocortical cells moro potently than IGF-I; 2) this effect is mediated through interaction of TGF-II with the TGF-I receptor; 3) bovine adrenocortical cells synthesize various IGFBPs that are induced differentially by ACTH; and 4) IGFBPs apparently play a modulatory role in IGF-induced stimulation of adrenal steroidogenesis. Therefore, bovine adult adrenocortical cells provide a useful tissue culture model in which the interactions among locally produced IGFs, IGFBPs, and the IGF-I receptor can be evaluated.
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页码:3714 / 3720
页数:7
相关论文
共 41 条
[1]  
ARAFAH BM, 1991, J LAB CLIN MED, P531
[2]   INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS [J].
CLEMMONS, DR .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 1990, 1 (08) :412-417
[3]   REGULATION OF INSULIN-LIKE GROWTH-FACTOR (IGF)-BINDING PROTEIN-SYNTHESIS BY INSULIN AND IGF-I IN CULTURED BOVINE FIBROBLASTS [J].
CONOVER, CA .
ENDOCRINOLOGY, 1990, 126 (06) :3139-3145
[4]   INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II - PEPTIDE, MESSENGER RIBONUCLEIC-ACID AND GENE STRUCTURES, SERUM, AND TISSUE CONCENTRATIONS [J].
DAUGHADAY, WH ;
ROTWEIN, P .
ENDOCRINE REVIEWS, 1989, 10 (01) :68-91
[5]   INSULIN-LIKE GROWTH-FACTOR (IGF)-II BINDING TO IGF-BINDING PROTEINS AND IGF RECEPTORS IS MODIFIED BY DELETION OF THE N-TERMINAL HEXAPEPTIDE OR SUBSTITUTION OF ARGININE FOR GLUTAMATE-6 IN IGF-II [J].
FRANCIS, GL ;
APLIN, SE ;
MILNER, SJ ;
MCNEIL, KA ;
BALLARD, FJ ;
WALLACE, JC .
BIOCHEMICAL JOURNAL, 1993, 293 :713-719
[6]   INHIBITORY EFFECT OF SOMATOMEDIN-C INSULIN-LIKE GROWTH FACTOR-I ON ADRENOCORTICOTROPIN-INDUCED OR FORSKOLIN-INDUCED STEROIDOGENESIS IN ISOLATED RAT ADRENOCORTICAL-CELLS [J].
FUJII, H ;
IIDA, S ;
TSUGAWA, M ;
GOMI, M ;
MORIWAKI, K ;
TARUI, S .
ENDOCRINOLOGY, 1990, 126 (01) :26-30
[7]   PRELIMINARY-OBSERVATIONS OF BOVINE ADRENAL FASCICULATA-RETICULARIS CELLS IN MONOLAYER-CULTURE - STEROIDOGENESIS, EFFECT OF ACTH AND CYCLIC AMP [J].
GOODYER, CG ;
TORDAY, JS ;
SMITH, BT ;
GIROUD, CJP .
ACTA ENDOCRINOLOGICA, 1976, 83 (02) :373-385
[8]   INSULIN-LIKE GROWTH FACTOR-II (IGF-II) MESSENGER-RIBONUCLEIC-ACID IS EXPRESSED IN STEROIDOGENIC CELLS OF THE DEVELOPING OVINE ADRENAL-GLAND - EVIDENCE OF AN AUTOCRINE PARACRINE ROLE FOR IGF-II [J].
HAN, VKM ;
LU, F ;
BASSETT, N ;
YANG, KP ;
DELHANTY, PJD ;
CHALLIS, JRG .
ENDOCRINOLOGY, 1992, 131 (06) :3100-3109
[9]   EXPRESSION OF SOMATOMEDIN INSULIN-LIKE GROWTH-FACTOR MESSENGER RIBONUCLEIC-ACIDS IN THE HUMAN-FETUS - IDENTIFICATION, CHARACTERIZATION, AND TISSUE DISTRIBUTION [J].
HAN, VKM ;
LUND, PK ;
LEE, DC ;
DERCOLE, AJ .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1988, 66 (02) :422-429
[10]  
HONEGGER A, 1986, J BIOL CHEM, V261, P569