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.
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
Andreas
A
Institutes of Molecular Animal Breeding/Gene Center, Ludwig-Maximilian University, Munich, Germany.
Weber
Matthias M
MM
Fisch
Thomas
T
Nedbal
Sabine
S
Fottner
Christian
C
Elmlinger
Martin W
MW
Wanke
Rüdiger
R
Wolf
Eckhard
E
D000311:Adrenal Glands / Q000378:metabolism* / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001835:Body Weight; D003345:Corticosterone / Q000097:blood; D015870:Gene Expression; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006965:Hyperplasia; D006984:Hypertrophy; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics; D011986:Receptors, Somatotropin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D017526:Receptor, IGF Type 1; D003345:Corticosterone