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.
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.
复制标题
胰岛素样生长因子 II (IGF-II) 在刺激培养的牛肾上腺皮质细胞分泌皮质醇方面比 IGF-I 更有效:与 IGF-I 受体和 IGF 结合蛋白相互作用。
作者:
M. Weber;Pia Simmler;C. Fottner;D. Engelhardt
Although the stimulating effect of insulin-like growth factor I (IGF-I) on adrenal steroidogenesis has been well established, the role 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-II (13 nM) synergistically increased cortisol secretion from 1-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 [Arg54,55]IGF-II, which only binds to the IGF-I receptor, was equipotent to native IGF-II, whereas [Leu27]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, [des1-3]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 [des1-6]IGF-II. In conclusion, these results demonstrate that 1) IGF-II stimulates basal as well as ACTH-induced cortisol secretion from bovine adrenocortical cells more potently than IGF-I; 2) this effect is mediated through interaction of IGF-II with the IGF-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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DOI:
10.1210/jcem.77.3.8396578
发表时间:
1993
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
作者:
Mesiano,S;Jaffe,RB
通讯作者:
Jaffe,RB
DOI:
--
发表时间:
1990
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
Townsend,SF;Dallman,MF;Miller,WL
通讯作者:
Miller,WL
DOI:
10.1210/jcem.76.4.8473412
发表时间:
1993-04
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
作者:
S. Mesiano;S. Mellon;R. Jaffe
通讯作者:
S. Mesiano;S. Mellon;R. Jaffe
DOI:
--
发表时间:
1988
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
Kiess,W;Blickenstaff,GD;Sklar,MM;Thomas,CL;Nissley,SP;Sahagian,GG
通讯作者:
Sahagian,GG
DOI:
10.1016/s0021-9258(18)54755-4
发表时间:
1991-11
期刊:
The Journal of biological chemistry
影响因子:
--
作者:
K. Sakano;T. Enjoh;F. Numata;H. Fujiwara;Y. Marumoto;N. Higashihashi;Y. Sato;J. Perdue;Y. Fujita‐Yamaguchi
通讯作者:
K. Sakano;T. Enjoh;F. Numata;H. Fujiwara;Y. Marumoto;N. Higashihashi;Y. Sato;J. Perdue;Y. Fujita‐Yamaguchi