Receptor autoradiographic localization of insulin-like growth factor-I (IGF-I) binding sites in human fetal and adult adrenal glands

Shigematsu, Kazuto; Níwa, Masami; Kurihara, Masaki; Yamashita, Kimihiro; Kawai, Kioko; Tsuchiyama, Hideo

doi:10.1016/0024-3205(89)90624-3

Cited by 33 publications

(19 citation statements)

References 23 publications

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“…In our study, the presence of IGF1-R is associated to a better prognosis (Bonneterre et al, 1990). Conversely, IGF1-R are found less frequently and at lower concentrations in benign breast diseases (Peyrat et al, 1988b (Israel et al, 1984;Bohannon et al, 1986), the adrenal gland (Shigematsu et al, 1989) and the ovary (Monget et al, 1989).…”

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confidence: 45%

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Insulin-like growth factor 1 receptors in human breast tumour: Localisation and quantification by histo-autoradiographic analysis

Jammes¹,

Jp²,

Ban³

et al. 1992

Br J Cancer

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To assess the precise role of IGF1 in benign and malignant breast diseases, we analysed the tissular localisation, characterised, and quantified specific insulin-like growth factor 1 (IGF1) binding sites in these heterogenous tissues, using histo-autoradiographic analysis (HAA). The 125I-IGF1 binding was performed on frozen tissue sections and analysed using 3H Ultrofilm autoradiography coupled to computerised image analysis. Competitive binding experiments using unlabelled IGF1, IGF2 and insulin showed that the tissues exhibited typical type I IGF binding sites. This specificity was confirmed by the use of alpha IR-3 monoclonal antibody, as inhibitor of 125I-IGF1 binding. IGF1 binding sites were detected in 18 human primary breast cancers, 12 benign breast tumours and two normal breast tissues. Using HAA we found that the human breast carcinomas studied exhibit a specific and high binding capacity for 125I-IGF1 exclusively localised on the proliferative epithelial component. The 125I-IGF1 binding activity of benign breast tumours or normal breast tissue was significantly lower than in cancerous tissues. There was a significant correlation between IGF1-R concentrations detected with HAA and those detected with a classical biochemical method. Moreover, HAA could be useful in further detailing whether a tumour is IGF1-R positive or negative HAA appears to be a useful method for the detection of growth factor receptors, specially in small biopsy specimens. Images Figure 2 Figure 3

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confidence: 45%

“…Quantitative IGFJ-R autoradiography Frozen sections (7 pm) were processed as previously described (Haour et al, 1987 (1986) and Shigematsu et al (1989). Non-specific binding was determined in the presence of 5 x 10-7 M IGF1.…”

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confidence: 99%

Insulin-like growth factor 1 receptors in human breast tumour: Localisation and quantification by histo-autoradiographic analysis

Jammes¹,

Jp²,

Ban³

et al. 1992

Br J Cancer

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“…Accumulating data indicate that the IGF system plays a role in the regulation of growth and differentiation of the adrenal gland (Penhoat et al 1989, Reed & James 1989. Previous studies have demonstrated the presence of IGF-I and IGF-II mRNA or peptides, both IGF receptors and various IGFBPs in the adrenal gland of several species, including humans (Pillion et al 1988, Shigematsu et al 1989, Townsend et al 1990, Arafah 1991, Han et al 1992, Weber et al 1994. Furthermore, IGFs have been found to elicit mitogenic and differentiating effects on adrenocortical cells in vitro (Penhoat et al 1989, Pham-Huu-Trung et al 1991, Weber et al 1995.…”

Section: Introductionmentioning

confidence: 99%

Regulation of steroidogenesis by insulin-like growth factors (IGFs) in adult human adrenocortical cells: IGF-I and, more potently, IGF-II preferentially enhance androgen biosynthesis through interaction with the IGF-I receptor and IGF-binding proteins

Fottner¹,

Engelhardt²,

Weber³

1998

Journal of Endocrinology

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Although the effect of insulin-like growth factors (IGFs) in fetal adrenocortical cells has been investigated extensively, the role of the IGF system in the adult human adrenal gland remains unclear. In the present study we investigated the effect of recombinant human IGF-I and IGF-II on cortisol, dehydroepiandrosterone sulfate (DHEA-S) and cAMP synthesis in adult human adrenocortical cells in primary culture. Both IGFs stimulate basal as well as adrenocorticotropin (ACTH)-induced steroid secretion in a time-and dose-dependent fashion. While both IGFs (6·5 nM) induced only a moderate 2-fold increase in basal cortisol output after 48 h, the effect on basal DHEA-S secretion was significantly stronger, with a 2·7-and 3·7-fold stimulation by IGF-I and IGF-II respectively. Similarly, IGF-II enhanced ACTH-induced cortisol and DHEA-S secretion more potently than IGF-I. In doseresponse experiments, the maximum stimulation of ACTH-induced DHEA-S secretion was induced by 1·6 nM IGF-I (2-fold increase) or IGF-II (2·9-fold increase), while the maximum response of cortisol secretion was elicited only at 13 nM IGF-I (2-fold increase) or IGF-II (2·5-fold increase). This resulted in a significant shift of the DHEA-S dose-response curves to the left, indicating a relative selective stimulation of androgen biosynthesis by physiologically low concentrations (0·4-3·2 nM) of IGF-II, and less potently by IGF-I. At all doses tested, the steroidogenic effect of IGF-II was significantly stronger than the effect of IGF-I. Although both IGF receptors are present in adult human adrenocortical cells, the steroidogenic effect of IGF-II is mediated through the IGF-I receptor, since [Arg 54,55 ]IGF-II, which only binds to the IGF-I receptor, was equipotent with native IGF-II, whereas [Leu 27 ]IGF-II, which preferentially binds to the type II IGF receptor, did not show any effect. In addition, [des 1-3 ]IGF-I, which exhibits only minimal binding to IGFBPs, was significantly more potent than native IGF-I in stimulating adrenal steroid biosynthesis, and elicited almost the same maximum stimulatory effect as IGF-II and [des [1][2][3][4][5][6] ]IGF-II. By Western ligand blotting of conditioned medium it was shown that adult human adrenocortical cells secrete various IGF-binding proteins (IGFBPs), which are induced differentially by treatment with ACTH. In conclusion, these results demonstrate that: (1) IGF-II stimulates basal as well as ACTH-induced DHEA-S and cortisol secretion from adult human adrenocortical cells more potently than IGF-I; (2) both IGFs predominantly stimulate androgen biosynthesis; (3) the steroidogenic effect of IGF-I and IGF-II is mediated through interaction with the IGF-I receptor; (4) the different steroidogenic potency of IGF-I and IGF-II might be explained by interaction of these ligands with locally produced IGFBPs. These data indicate that the IGF system plays an important role in the regulation of the differentiated function of adult human adrenocortical cells.

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“…After ACTH stimulation or sodium restriction, the translation of IGF-I mRNA is enhanced in zona glomerulosa, also supporting a local proliferative role for IGF-I. This seems plausible as IGF-I receptors have been identified in rat, bovine and human adrenal glands (Penhoat et al 1988, Shigematsu et al 1989, Arafah 1991, Weber et al 1995, 1997. In our experiments, IGF-I administration increased the extent of IZAg non-expressing cells in the subcapsular area, suggesting its particular modulatory role in the peripheral areas of the regenerated adrenal cortex.…”

Section: Discussionmentioning

confidence: 95%

Effects of prolonged infusion of basic fibroblast growth factor and IGF-I on adrenocortical differentiation in the autotransplanted adrenal: an immunohistochemical study

Vendeira

Pignatelli²,

Neves³

et al. 1999

Journal of Endocrinology

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Adrenocortical regeneration after adrenal autotransplantation provides a model for the study of local autocrine/ paracrine mechanisms involved in the growth and differentiation of the adrenal cortex. To study the possible involvement of some growth factors, namely basic fibroblast growth factor (bFGF, FGF-2) and insulin-like growth factor I (IGF-I), in cell differentiation, immunohistochemical and ultrastructural studies were carried out on adrenal autotransplants in adult male rats. To distinguish between fasciculata and glomerulosa-like cells with accuracy, tissue sections were immunostained with IZAb, which recognizes the inner zone antigen (IZAg) present in fasciculata and reticularis cells but absent from the glomerulosa, and by electron microscopy. IGF-I-treated animals exhibited a clear glomerulosa-like zone that was devoid of IZAb immunostaining. In this outer subcapsular area, ultrastructural examination showed cells containing mitochondria with irregular cristae resembling those of the fetal or immature glomerulosa cells. In contrast, no significant morphological differences were observed in bFGF-treated animals when compared with those from saline-treated controls, in both of which, IZAb immunostaining occurred in almost all adrenocortical cells, with no clear zonation or glomerulosa, as seen in the intact animal. Plasma aldosterone and corticosterone concentrations were lower in autotransplanted control animals than in intact controls, although plasma renin activities were similar. IGF-I treatment significantly increased aldosterone concentrations, whereas corticosterone and plasma renin activity were reduced. bFGF infusion further reduced plasma aldosterone, although plasma renin activity and corticosterone were unaffected. These results suggest that the two growth factors have different effects on zonal differentiation and function in the autotransplanted gland. In particular, bFGF, by reducing glomerulosa function, appears partly to replicate the actions of ACTH in normal animals. In contrast, IGF-I enhances the glomerulosa secreting phenotype and diminishes that of the fasciculata/ reticularis, possibly replicating the actions of angiotensin II or a low sodium diet.

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Receptor autoradiographic localization of insulin-like growth factor-I (IGF-I) binding sites in human fetal and adult adrenal glands

Cited by 33 publications

References 23 publications

Insulin-like growth factor 1 receptors in human breast tumour: Localisation and quantification by histo-autoradiographic analysis

Insulin-like growth factor 1 receptors in human breast tumour: Localisation and quantification by histo-autoradiographic analysis

Regulation of steroidogenesis by insulin-like growth factors (IGFs) in adult human adrenocortical cells: IGF-I and, more potently, IGF-II preferentially enhance androgen biosynthesis through interaction with the IGF-I receptor and IGF-binding proteins

Effects of prolonged infusion of basic fibroblast growth factor and IGF-I on adrenocortical differentiation in the autotransplanted adrenal: an immunohistochemical study

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