Morphological and Histopathological Changes in Tongues of Experimentally Developed Acromegaly-like Rats

Abstract

An acromegaly-like rat model recently developed by exogenous administration of insulin-like growth factor I (IGF-I) was used to investigate morphological and histopathological tongue changes and clarify whether the changes were reversible. Human recombinant IGF-I (640 µg/day) was continuously subcutaneously infused into ten-week-old male rats for four weeks (IGF-I group; n = 6). Control sham-operated animals were injected saline alone (control group; n = 6). Rats were sacrificed immediately on ending administration at the age of fourteen weeks. Another 12 rats (6 from each group) were housed for an additional four weeks after administration ended. Total IGF-I (human + rat) increased significantly during administration, returning to control levels afterwards. Tongue weights significantly increased with histopathological changes present (increases in the muscle-bundle width, spaces between muscle-bundles and epithelium thickness) in the IGF-I group compared to control rats. Tongue size returned to control levels after discontinuation of IGF-I administration. These findings suggest that the characteristic tongue enlargement was developed experimentally in our acromegaly-like rat model, and that such morphological and histopathological tongue changes are reversible on normalization of circulating IGF-I levels.

Key words

Acromegaly - rat model - IGF-I - tongue enlargement - oral soft tissues

References

• 1 Ardran G M, Kemp F H. The tongue and mouth in acromegaly.  Clin Radiol. 1972;  23 434-444
• 2 Kole H. Results, experience, and problems in the operative treatment of anomalies with reverse overbite (mandibular protruction).  Oral Surg Oral Med Oral Pathol. 1965;  19 427-450
• 3 Kunzler A, Farmand M. Typical changes in the viscerocranium in acromegaly.  J Craniomaxillofac Surg. 1991;  19 332-340
• 4 Wittmann A-L. Macroglossia in acromegaly and hypothyroidism.  Virchows Arch A Pathol Anat Histol. 1977;  373 353-360
• 5 Iikubo M, Ikeda H, Kobayashi A, Kojima I, Hashimoto K, Sakamoto M, Sasano T. Insulin-like growth factor-I stimulates acromegaly-like specific mandibular enlargement in rats.  Horm Metab Res. 2004;  36 696-701
• 6 Van Wyk J J. The somatomedins: biological actions and physiologic control mechanism. In: Li CH (ed) Hormonal proteins and peptides. Massachusetts; Chestnut Hill 1984: 81-125
• 7 Melmed S. Acromegaly.  N Engl J Med. 1990;  322 966-977
• 8 Phillip D KL, Bonita K B, Frances L, Elain Y WK, Raymond L H. A homologous radioimmunoassay for rat insulin-like growth factor-I (IGF-I): implications for studies of human IGF-I physiology.  J Clin Endocrinol Metab. 1996;  81 2002-2005
• 9 Zhao G, Monier-Fauger M C, Langub M C, Geng Z, Nakayama T, Pike J W, Chernausek S D, Rosen C J, Donahue L R, Malluche H H, Eagin J A, Clemens T L. Targeted overexpression of insulin-like growth factor I to osteoblast of transgenic mice: increased trabecular bone volume without increased osteoblast proliferation.  Endocrinology. 2000;  141 2678-2682
• 10 Malpe R, Baylink D J, Linkhart T A, Wergedal J E, Mohan S. Insulin-like growth factor (IGF)-I, -II, IGF binding proteins (IGFBP)-3, -4, and -5 levels in the conditioned media of normal human bone cell are skeletal site-dependent.  J Bone Miner Res. 1997;  12 423-430
• 11 Semsarian C, Sutrave P, Richmond D R, Graham R M. Insulin-like growth factor-I induces myotube hypertrophy associated with an increase in anaerobic glycolysis in a clonal skeletal-muscle cell model.  Biochem J. 1999;  339 443-451
• 12 Barton-Davis E R, Shoturma D I, Musaro A, Rosenthal N, Sweeney H L. Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function.  Proc Natl Acad Sci USA. 1998;  95 15 603-15 607
• 13 Mathews L S, Hammer R E, Brinster R L, Palmiter R D. Expression of insulin-like growth factor I in transgenic mice with elevated level of growth hormone is correlated with growth.  Endcrinology. 1988;  123 2827-2833
• 14 Allen R E, Boxhorn L K. Regulation of skeletal muscle satellite cell proliferation and differentiation by transforming growth factor-beta, insulin-like growth factor I, and fibroblast growth factor.  J Cell Physiol. 1989;  138 311-315
• 15 Ikkos D, Luft R, Sjogren B. Body water and sodium in patients with acromegaly.  J Clin Invest. 1954;  33 989-994
• 16 Palmieri G, Ikkos D. Water and electrolyte content of muscle in Acromegaly.  Acta Endocrinol (Copenh). 1965;  48 469-472
• 17 Landin K, Petruson B, Jakobsson K-E, Bengtsson B-A. Skeletal muscle sodium and potassium changes after successful surgery in Acromegaly: relation to body composition, blood glucose, plasma insulin and blood pressure.  Acta Endocrinol (Copenh). 1993;  128 418-422
• 18 Bengtsson B-A, Brummer R-J, Eden S, Bosaeus I, Lindstedt G. Body composition in acromegaly: the effect of treatment.  Clin Endocrinol (Oxf). 1989;  31 482-490
• 19 Dorup I, Clausen T. Insulin-like growth factor I stimulates active Na+-K+ transport in rat soleus muscle.  Am J Physiol. 1995;  268(5 Pt 1) E849-E857
• 20 Brummer R-J, Lonn L, Kvist H, Grangard U, Bengtosson B-A, Sjostrom L. Adipose tissue and muscle volume determination by computed tomography in acromegaly, before and 1 year after adenomectomy.  Eur J Clin Invest. 1993;  23 199-205