Aim: The aim of this study was to estimate the lipolytic activity of the human growth hormone variant, 20-kD human growth hormone (20K-hGH). Methods: Obese KV-Ay mice were given daily subcutaneous injections of 20K-hGH (0.25, 0.5, 1.0 mg/kg), 22K-hGH (0.25 mg/kg) or saline as a control for 2 weeks. Body composition (fat, water and protein), lipolysis and lipoprotein lipase (LPL) activity were measured 24 h after the final injection. Results: Both growth hormone isoforms significantly reduced relative fat pad and whole body lipids. In addition, 20K-hGH produced an inhibition of LPL activity in adipose tissue and stimulated lipolysis in adipocytes. Conclusion: These data strongly suggest that inhibition of LPL activity in adipose tissue and stimulation of lipolysis in adipocytes by 20K-hGH treatment reduce adipose tissue mass, resulting in body fat reduction.

1.
Lewis UJ, Dunn JT, Bonewald LF, Seavey BK, VanderLaan WP: A naturally occurring structural variant of human growth hormone. J Biol Chem 1978;253:2679–2687.
2.
Ishikawa M, Yokoya S, Tachibana K, Hasegawa Y, Yasuda T, Tokuhiro E, Hashimoto Y, Tanaka T: Serum levels of 20-kilodalton human growth hormone (GH) parallel those of 22-kilodalton human GH in normal and short children. J Clin Endocrinol Metab 1999;84:98–104.
3.
Tsushima T, Katoh Y, Miyachi Y, Chihara K, Teramoto A, Irie M, Hashimoto Y: hGH SgoK: Serum concentration of 20K human growth hormone (20K hGH) measured by a specific enzyme-linked immunosorbent assay. J Clin Endocrinol Metab 1999;84:317–322.
4.
Uchida H, Naito N, Asada N, Wada M, Ikeda M, Kobayashi H, Asanagi M, Mori K, Fujita Y, Konda K, Kusuhara N, Kamioka T, Nakashima K, Honjo M: Secretion of authentic 20-kDa human growth hormone (20K hGH) in Escherichia coli and properties of the purified product. J Biotechnol 1997;55:101–112.
5.
Tsunekawa B, Wada M, Ikeda M, Uchida H, Naito N, Honjo M: The 20-kilodalton (kDa) human growth hormone (hGH) differs from the 22-kDa hGH in the effect on the human prolactin receptor. Endocrinology 1999;140:3909–3918.
6.
Wada M, Ikeda M, Takahashi Y, Asada N, Chang KT, Takahashi M, Honjo M: The full agonistic effect of recombinant 20 kDa human growth hormone (hGH) on CHO cells stably transfected with hGH receptor cDNA. Mol Cell Endocrinol 1997;133:99–107.
7.
Wada M, Uchida H, Ikeda M, Tsunekawa B, Naito N, Banba S, Tanaka E, Hashimoto Y, Honjo M: The 20-kilodalton (kDa) human growth hormone (hGH) differs from the 22-kDa hGH in the complex formation with cell surface hGH receptor and hGH-binding protein circulating in human plasma. Mol Endocrinol 1998;12:146–156.
8.
Satozawa N, Takezawa K, Miwa T, Takahashi S, Hayakawa M, Ooka H: Differences in the effects of 20 K- and 22 K-hGH on water retention in rats. Growth Horm IGF Res 2000;10:187–192.
9.
Takahashi S, Shiga Y, Satozawa N, Hayakawa M: Diabetogenic activity of 20-kilodalton growth hormone (20K-hGH) and 22K-hGH in rats. Growth Horm IGF Res 2001;11:110–116.
10.
Rosen T, Bengtsson B-A: Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 1990;336:285–288.
11.
Bates AS, Hoff W, Jones PJ, Clayton RN: The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab 1996;81:1169–1172.
12.
Bulow B, Hagmer L, Mikoczy Z, Nordstrom CH, Erfurth EM: Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol 1997;46:75–81.
13.
Markussis V, Beshyah SA, Fisher C, Sharo P, Nicolaides AN, Johnston DG: Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults. Lancet 1992;340:1188–1192.
14.
Asada N, Takahashi Y, Wada M, Naito N, Uchida H, Ikeda M, Honjo M: GH induced lipolysis stimulation in 3T3-L1 adipocytes stably expressing hGHR: Analysis on signaling pathway and activity of 20K hGH. Mol Cell Endocrinol 2000;162:121–129.
15.
Ishikawa M, Tachibana T, Kamioka T, Horikawa R, Katsumata N: Comparison of the somatogenic action of 20 kDa- and 22 kDa-human growth hormones in spontaneous dwarf rats. Growth Horm IGF Res 2000;10:199–206.
16.
Richelsen B: Action of growth hormone in adipose tissue. Horm Res 1997;48:105–110.
17.
Azain MJ, Hausman DB, Kasser TR, Martin RJ: Effect of somatotropin and feed restriction on body composition and adipose metabolism in obese Zucker rats. Am J Physiol 1995;269:E137–E144.
18.
Rodbell M: Metabolism of isolated fat cells. 1. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 1964;239:375–380.
19.
Kawamura I, Yamamoto N, Sakai F, Yamazaki H, Naoe Y, Inami M, Manda T, Shimomura K: Action of lipoprotein lipase and inhibition of B16 melanoma-induced cachexia in mice by ponalrestat, an aldose reductase inhibitor. Anticancer Res 1999;19:341–348.
20.
Clark RG, Mortensen F, Carlsson LMS, Carmignac D, Robinson ICAF: Growth responses to patterned GH delivery. Endocrine 1995;3:717–723.
21.
Johansson JO, Oscarsson J, Bjarnason R, Bengtsson BA: Two weeks of daily injections and continuous infusion of recombinant human growth hormone (GH) in GH-deficient adults. I. Effects on insulin-like growth factor-I (IGF-I), GH and IGF binding proteins, and glucose homeostasis. Metabolism 1996;45:362–369.
22.
Bates PC, Loughna PT, Pell JM, Schulster D, Millward DJ: Interactions between growth hormone and nutrition in hypophysectomized rats: Body composition and production of insulin-like growth factor-I. J Endocrinol 1993;139:117–126.
23.
Martin RJ, Drewry M, Jewell D, Harris RB, Young R, Patton JS: Growth hormone treatment reduces total body fat accumulation in Zucker obese rats. Int J Obes 1989;13:327–335.
24.
Holder AT, Blows JA, Aston R, Bates PC: Monoclonal antibody enhancement of the effects of human growth hormone on growth and body composition in mice. J Endocrinol 1988;117:85–90.
25.
Beauville M, Harant I, Crampes F, Riviere D, Tauber MT, Tauber JP, Garrigues M: Effect of long-term rhGH administration in GH-deficient adults on fat cell epinephrine response. Am J Physiol 1992;263:E467–E472.
26.
Yang S, Bjorntorp P, Liu X, Eden S: Growth hormone treatment of hypophysectomized rats increases catecholamine-induced lipolysis and the number of beta-adrenergic receptors in adipocytes: No differences in the effects of growth hormone on different fat depots. Obes Res 1996;4:471–478.
27.
Marcus C, Bolme P, Micha-Johansson G, Margery V, Bronnegard M: Growth hormone increases the lipolytic sensitivity for catecholamines in adipocytes from healthy adults. Life Sci 1994;54:1335–1341.
28.
Bergo M, Olivecrona G, Olivecrona T: Diurnal rhythms and effects of fasting and refeeding on rat adipose tissue lipoprotein lipase. Am J Physiol 1996;271:E1092–E1097.
29.
Olivecrona T, Bengtsson G: Immunochemical properties of lipoprotein lipase. Development of an immunoassay applicable to several mammalian species. Biochim Biophys Acta 1983;752:38–45.
30.
Ottosson M, Vikman-Adolfsson K, Enerback S, Elander A, Bjorntorp P, Eden S: Growth hormone inhibits lipoprotein lipase activity in human adipose tissue. J Clin Endocrinol Metab 1995;80:936–941.
31.
Oscarsson J, Ottosson M, Johansson JO, Wiklund O, Marin P, Bjorntorp P, Bengtsson BA: Two weeks of daily injections and continuous infusion of recombinant human growth hormone (GH) in GH-deficient adults. II. Effects on serum lipoproteins and lipoprotein and hepatic lipase activity. Metabolism 1996;45:370–377.
32.
Murase T, Yamada N, Matsuzaki F: The in vitro effect of growth hormone on adipose tissue lipoprotein lipase in rats. Life Sci 1981;28:199–201.
33.
Barber MC, Clegg RA, Finley E, Vernon RG, Flint DJ: The role of growth hormone, prolactin and insulin-like growth factors in the regulation of rat mammary gland and adipose tissue metabolism during lactation. J Endocrinol 1992;135:195–202.
34.
Richelsen B, Pedersen SB, Borglum JD, Moller-Pedersen T, Jorgensen J, Jorgensen JO: Growth hormone treatment of obese women for 5 weeks: Effect on body composition and adipose tissue LPL activity. Am J Physiol 1994;266:E211–E216.
35.
Uchida H, Banba S, Wada M, Matsumoto K, Ikeda M, Naito N, Tanaka E, Honjo M: Analysis of binding proterties between 20 kDa human growth hormone (hGH) and hGH receptor (hGHR): The binding affinity for hGHR extracellular domain and mode of receptor dimerization. J Mol Endocrinol 1999;23:347–353.
36.
Barnard R, Rowlinson SW, Waters MJ: Soluble forms of the rabbit adipose tissue and liver growth hormone receptors are antigenically identical, but the integral membrane forms differ. Biochem J 1990;267:471–477.
37.
Frick GP, Tai LR, Baumbach WR, Goodman HM: Tissue distribution, turnover, and glycosylation of the long and short growth hormone receptor isoforms in rat tissues. Endocrinology 1998;139:2824–2830.
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