Effects of insulin-like growth factor I (IGF-I) on enzymatic activity in human adrenocortical cells. Interactions with ACTH

Pham-Huu-Trung, M T; Villette, Jean‐Marie; Bogyo, A.; Duclos, J M; Fiet, Jean; Binoux, M

doi:10.1016/0960-0760(91)90348-9

Cited by 36 publications

(24 citation statements)

References 23 publications

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“…The steroidogenic effect of IGF-I in adult human adrenocortical cells reported in this study is consistent with previous reports of an IGF-I-stimulated steroidogenic response in bovine, ovine and human adrenocortical cells (Penhoat et al 1989, Reed & James 1989, Pepe & Albrecht 1990, Pham-Huu-Trung et al 1991, Weber et al 1995, L Allemand et al 1996. However, little information is available on the effect of IGF-II in the adult human adrenal gland.…”

Section: Discussionsupporting

confidence: 82%

“…In bovine adrenocortical cells, IGF-I upregulates ACTH receptors, while ACTH increases the abundance of IGF-I receptors and the secretion of IGFs (Penhoat et al 1989, Reed & James 1989, Pepe & Albrecht 1990, Pham-Huu-Trung et al 1991. In human adrenocortical cells, IGF-I induces synthesis of the mRNA of key steroidogenic enzymes and slightly increases ACTH receptor mRNA (L'Allemand et al 1996, Kristiansen et al 1997.…”

Section: Discussionmentioning

confidence: 99%

“…Increased levels of IGF-II mRNA are found in adrenocortical carcinomas (Voutilainen & Miller 1987, Ilvesmäki et al 1993, Gicquel et al 1994. However, scant information is available on the effect of IGFs in adult human adrenocortical cells (Pham-Huu-Trung et al 1991, Kristiansen et al 1997, and the role of the IGF-II receptors in IGF-II signaling in the adult human adrenal gland remains unclear (L'Allemand et al 1996).…”

Section: Introductionmentioning

confidence: 99%

“…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. In the fetal human adrenal gland, both IGFs stimulate cell proliferation, and IGF-II in combination with estrogen directs steroidogenesis toward androgen biosynthesis .…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Adult human adrenocortical glands express IGF-I, to a lesser extent IGF-II, and both types of the IGF receptor (Weber et al 1997). Furthermore, IGFs elicit mitogenic as well as differentiating effects in adrenocortical cells in vitro (Pham-Huu-Trung et al 1991, L'Allemand et al 1996, Kristiansen et al 1997, and an overexpression of IGF-I receptors, IGF-II and IGFBP-2 has been described in adrenocortical carcinomas (Voutilainen & Miller 1987, Ilvesmäki et al 1993, Gicquel et al 1994, Boulle et al 1998). Previously, we have shown that IGF-II -through interaction with the IGF-I receptor -stimulates basal as well as adrenocorticotropin (ACTH)-induced steroid secretion from adult human and bovine adrenocortical cells more potently than IGF-I, and that the different potency of IGF-I and IGF-II is presumably due to an interaction of the ligands with locally produced IGFBPs (Weber et al 1995.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of insulin-like growth factor (IGF)-binding protein expression and secretion by adult human adrenocortical cells: differential regulation by IGFs and adrenocorticotropin

Fottner

Engelhardt²,

Elmlinger³

et al. 2001

Journal of Endocrinology

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In previous studies we have shown that IGF-II stimulates basal as well as ACTH-induced cortisol secretion from adult human adrenocortical cells more potently than IGF-I, and that both IGFs predominantly stimulate androgen biosynthesis. The steroidogenic effect of IGF-I and IGF-II is mediated through interaction with the IGF-I receptor, and modified by locally produced IGF-binding proteins (IGFBPs). In the present study, we identified and characterized IGFBP synthesis in normal adult human adrenocortical cells in primary culture, and investigated the effect of ACTH and recombinant human IGF-I and -II on the regulation of IGFBP expression and secretion.Using RT-PCR, we identified the mRNA of all six high-affinity IGFBPs, in both adrenocortical tissue and monolayer cell cultures of adrenocortical cells. Using Western ligand and immunoblotting and two-dimensional Western ligand blotting we confirmed the secretion of IGFBP-1, -2, -3, -4 and -5 by adrenocortical cells in primary culture.The quantification of IGFBPs indicated that IGFBP-3 accounts for almost half the binding activity in conditioned medium of unstimulated cells (47%), followed by IGFBP-4 (20%), IGFBP-5 (15%), IGFBP-2 (12%) and IGFBP-1 (6%). After treatment with ACTH, the abundance of IGFBP-1 was upregulated significantly 2·6-fold, while IGFBP-3 was induced only slightly (1·3-fold). IGFBP-2, -4 and -5 remained unchanged. In contrast, IGF-I and -II (6·5 nM) predominantly induced the abundance of IGFBP-5 (2-and 1·6-fold respectively) and IGFBP-3 (2-and 1·7-fold respectively), while IGFBP-1, -2 and -4 were unaltered. The induction of IGFBP-1 and -5 by ACTH and IGFs, respectively, was paralleled by an increase in the amount of IGFBP-1 and -5 mRNA in these cells.In conclusion, all six high-affinity IGFBPs are expressed in the adult human adrenal gland, and the presence of at least five high-affinity IGFBPs has been demonstrated in conditioned medium of adult human adrenocortical cells. Furthermore, the expression and secretion of IGFBP-1 is upregulated by ACTH, whereas IGFBP-5 is induced by IGF-I and -II. Together with earlier findings, these results suggest that IGFBPs play an important modulatory role in the regulation of the differentiated adrenocortical function.

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Correlation Between Serum Levels of Insulin-like Growth Factor 1, Dehydroepiandrosterone Sulfate, and Dihydrotestosterone and Acne Lesion Counts in Adult Women

Cappel

Mauger²,

Thiboutot

2005

Archives of Dermatology

190

138

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Effects of insulin-like growth factor I (IGF-I) on enzymatic activity in human adrenocortical cells. Interactions with ACTH

Cited by 36 publications

References 23 publications

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

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

Identification and characterization of insulin-like growth factor (IGF)-binding protein expression and secretion by adult human adrenocortical cells: differential regulation by IGFs and adrenocorticotropin

Correlation Between Serum Levels of Insulin-like Growth Factor 1, Dehydroepiandrosterone Sulfate, and Dihydrotestosterone and Acne Lesion Counts in Adult Women

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