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Characterization of Insulin-Like Growth Factor I and Insulin Receptors on Cultured Bovine Adrenal Fasciculata Cells. Role of these Peptides on Adrenal Cell Function^*

INSERM U 307, Hopital Debrousse 69322 Lyon Cedex 05, France

Address requests for reprints to: Dr. A. Penhoat, INSERM U 307, Hopital Debrousse, 69322 Lyon Cedex 05, France.

Abstract

We have characterized insulin-like growth factor I (IGF-I) and insulin receptors in cultured bovine adrenal cells by binding and cross-linking affinity experiments. At equilibrium the dissociation constant and the number of binding sites per cell for IGF-I were 1.4 ± (SE) 0.3 x 10^-9 M and 19,200 ± 2,100, respectively. Under reduction conditions, disuccinimidyl suberate cross-linked [¹²⁵I]iodo-IGF-I to one receptor complex with an Mr of 125,000. Adrenal cells also contain specific insulin receptors with an apparent dissociation constant (K_d) of 10^-9 M. Under reduction conditions [¹²⁵I]iodo-insulin binds to one band with an approximate Mr of 125,000. IGF-I and insulin at micromolar concentrations, but not at nanomolar concentrations, slightly stimulated DNA synthesis, but markedly potentiated the mitogenic action of fibroblast growth factor. Adrenal cells cultured in a serum-free medium containing transferrin, ascorbic acid, and insulin (5 ng/vtA) maintained fairly constant angiotensin-II (A-II) receptor concentration per cell and increased cAMP release on response to ACTH and their steroidogenic response to both ACTH and A-II. When the cells were cultured in the same medium without insulin, the number of A-II receptors significantly decreased to 65% and the increased responsiveness was blunted. Treatment of such cells for 3 days with increasing concentrations of IGF-I (1-100 ng/ml) produced a 2- to 3-fold increase in A-II receptors and enhanced the cAMP response (3- to 4-fold) to ACTH and the steroidogenic response (4- to 6-fold) to ACTH and A-II. These effects were time and dose dependent (ED₅₀ = 10_-9 M). Insulin at micromolar concentrations produced an effect similar to that of IGF-I, but at nanomolar concentrations the effect was far less. The enhanced steroidogenic responsiveness of IGF-I and insulin-treated cells were related to an enhanced capacity to produce pregnenolone and an increased activity of several steroid hydroxylases. These results indicate that both IGF-I and insulin, acting through their own receptor, play an important role in the maintenance of specific adrenal cell functions. However, at physiological concentrations IGF-I is more potent than insulin. (Endocrinology 122: 2518–2526, 1988)

Footnotes

^* This work was supported by grants from La Ligue Francaise contre le Cancer and Fondation pour la Recherche en Hormonologie.

Received July 3, 1987.

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