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Institutes of Molecular Animal Breeding/Gene Center and
* Veterinary Pathology, Ludwig-Maximilian University, Munich, Germany;
Laboratory of Endocrine Research, Medical Department II Köln-Merheim, University of Cologne, Germany; and
Laboratory of Endocrine Research, University Children’s Hospital, Tuebingen, Germany
1Correspondence: Institute of Molecular Animal Breeding/Gene Center, Ludwig-Maximilian University, Feodor-Lynen-Str. 25, 81377 Munich, Germany. E-mail: ewolf{at}lmb.uni-muenchen.de
GH and IGF-I are capable of inducing cellular hypertrophy and/or hyperplasia. Chronic overexpression of GH in transgenic mice results in systemically and locally increased IGF-I levels and in disproportionate overgrowth, including adrenocortical enlargement and corticosterone hypersecretion. Using PEPCK-bovine GH transgenic (G) mice, we demonstrate that adrenal enlargement involves both hypertrophy (44%) and hyperplasia (50%) of zona fasciculata cells. To clarify whether IGFBP-2 affected cell volume and number, we crossed hemizygous G mice with hemizygous CMV-IGFBP-2 transgenic (B) mice, generating G mice, B mice, GB double transgenic mice, and nontransgenic controls (C). The absolute weight of the adrenal glands was significantly increased in 5-wk- and 4-month-old G mice vs. C and B mice. IGFBP-2 overexpression in GB mice reduced this effect of GH excess by 26% and 37% in 5-wk- and 4-month-old animals, respectively. GH-induced hypertrophy of zona fasciculata cells was completely abolished by IGFBP-2 overexpression in GB mice whereas hyperplasia was not affected. Basal and ACTH-induced plasma corticosterone levels of 4-month-old G mice, but not of GB mice, were two- to threefold increased compared with C mice. Plasma ACTH levels were similar in all groups. Our data show that IGFBP-2 potently separates hypertrophic and hyperplastic effects of GH/IGF-I excess on adrenocortical cells.—Hoeflich, A., Weber, M. M., Fisch, T., Nedbal, S., Fottner, C., Elmlinger, M. W., Wanke, R., Wolf, E. Insulin-like growth factor binding protein 2 (IGFBP-2) separates hypertrophic and hyperplastic effects of growth hormone (GH)/IGF-I excess on adrenocortical cells in vivo.
Key Words: adrenal gland • hypertrophy • hyperplasia • growth hormone • IGF binding protein 2 • transgenic mouse • corticosterone
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