Induction of Growth Hormone Release by Pueraria thunbergiana BENTH.

Abstract

Puerariae Radix (PR), Puerariae Flos (PF), and Puerariae Surculus (PS) as well as their constituents were tested for induction of rat growth hormone (rGH) release by both rat pituitary cell culture and in vivo experimentation in order to develop them to novel drugs. Through a calibration curve of the rGH released by addition of rat growth hormone-releasing hormone (rGHRH) to rat pituitary cells, the 70 % ethanol extracts of PR and PS increased rGH release by about 1.6 and 1.7 times as high, respectively, as the control group (264.6 ± 13.6 pM). However, each puerarin type as a representative constituent of PR in Korea Pharmacopeia (KP) and tectorigenin and an important ingredient of PF were twice as effective as in the control group. The acid hydrolysate of Puerariae Surculus (HPS) increased rGH release concentration-dependently, and its EC₅₀ was approximately 10.4 µg/ml. The T_max value for rGH after injection of 20 µg/kg of rGHRH was 10 - 30 min, while the C_max value was increased by approximately 12-fold compared to the control group (198.2 ± 25.0 pM) and the AUC_{0 - 45} was increased to 10 times the level of the control group (10,840.9 ± 845.5 min. pM). On the other hand, T_max for the HPS was 60 min, while C_max was increased approximately to 5.8 fold compared to control (244.1 ± 36.4 pM). C_max for puerarin was 1,028.6 ± 502.7 pM, that is, approximately 5.2 times as high as the control level. However, tectorigenin (20 µg/kg) was of no statistical significance. Therefore, we suggest that the HPS and puerarin act either on GH secretagogue receptors or on GHRH receptor of somatotrophin as possible agonists or an inhibitor on somatostatin receptor to release rGH, respectively.

Growth hormone (GH) - Growth hormone releasing hormone (GHRH) - Growth hormone secretagogue (GHS) - Pituitary cells - Puerariae Radix - Puerariae Surculus - Tectorigenin

References

• 1 Kim C, Ha H, Kim J S, Kim Y T, Kwon S-C, Park S W. Induction of Growth Hormone by the roots of Astragalus membraceus in Pituitary cell Culture.  Arch Pharm Res. 2003;  26 (1) 34-39
• 2 Kim C, Ha H, Kim H, Lee J H, Song K Y. Pueraria lobata O_HWL. as an Osteoporosis therapeutics.  Korean J Food Sci Technol. 2002;  34 (4) 710-718
• 3 Finch C E, Tanzi R E. Genetics of aging.  Science. 1997;  278 (5337) 407-411
• 4 Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach.  Nature. 1999;  402 (6762) 656-660
• 5 Bowers C Y, Momany F, Reynolds G A, Chang D, Hong A, Chang K. Structure-activity relationships of a synthetic pentapeptide that specifically releases growth hormone in vitro.  Endocrinology. 1980;  106 (3) 663-667
• 6 Gertz B J, Barrett J S, Eisenhandler R, Krupa D A, Wittreich J M, Seibold J R, Schneider S H. Growth hormone response in man to L-692,429, a novel nonpeptide mimic of growth hormone-releasing peptide-6.  J Clin Endocrinol Metab. 1993;  77 (5) 1393-1397
• 7 Argente J, Pozo J, Chowen J A. The growth hormone axis: control and effects.  Horm Res. 1996;  45 (Suppl 1) 9-11
• 8 Kim C, Shin S, Ha H, Kim J M. Study of substance changes in flowers of Pueraria thunbergiana BENTH. during storage.  Arch Pharm Res. 2003;  26 (2) 210-213
• 9 Bieglmayer C, Spona J, Schoeder R. Modulation of LH-RH stimulated gonadotropin release by progestagens and 17 beta-estradiol in primary pituitary cell culture.  Endocrinol Exp. 1980;  14 (3) 171-182
• 10 Sliutz G, Speiser P, Schultz A M, Spona J, Zeillinger R. Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.  Horm Metab Res. 1993;  25 (5) 253-255
• 11 Suter D E, Schwartz N B. Effects of glucocorticoids on secretion of luteinizing hormone and follicle-stimulating hormone by female rat pituitary cells in vitro.  Endocrinology. 1985;  117 (3) 849-854
• 12 Wehrenberg W B, Brazeau P, Luben R, Ling N, Guillemin R. A noninvasive functional lesion of the hypothalamo-pituitary axis for the study of growth hormone-releasing factor.  Neuroendocrinology. 1983;  36 (6) 489-491
• 13 Tannenbaum G S, Ling N. The interrelationship of growth hormone (GH)-releasing factor and somatostatin in generation of the ultradian rhythm of GH secretion.  Endocrinology. 1984;  115 (5) 1952-1957
• 14 Lesniak M A, Gorden P, Roth J, Gavin J R 3rd. Binding of 125I-human growth hormone to specific receptors in human cultured lymphocytes. Characterization of the interaction and a sensitive radioreceptor assay.  J Biol Chem. 1974;  249 (6) 1661-1667
• 15 Kiess W, Butenandt O. Specific growth hormone receptors on human peripheral mononuclear cells: reexpression, identification, and characterization.  J Clin Endocrinol Metab. 1985;  60 (4) 740-746
• 16 Hattori N, Saito T, Yagyu T, Jiang B H, Kitagawa K, Inagaki C. GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils.  J Clin Endocrinol Metab. 2001;  86 (9) 4284-4291
• 17 Cheng K, Chan W W, Barreto A Jr, Convey E M, Smith R G. The synergistic effects of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 on growth hormone (GH)-releasing factor-stimulated GH release and intracellular adenosine 3′,5′-monophosphate accumulation in rat primary pituitary cell culture.  Endocrinology. 1989;  124 (6) 2791-2798
• 18 Howard A D, Feighner S D, Cully D F, Arena J P, Liberator P A, Rosenblum C I, Hamelin M, Hreniuk D L, Palyha O C, Anderson J, Paress P S, Diaz C, Chou M, Liu K K, McKee K K, Pong S S, Chaung L Y, Elbrecht A, Dashkevicz M, Heavens R, Rigby M, Sirinathsinghji D J, Dean D C, Melillo D G, Van der Ploeg L HT. A receptor in pituitary and hypothalamus that functions in growth hormone release.  Science. 1996;  273 (5277) 974-977
• 19 De Marinis L, Mancini A, Valle D, Izzi D, Bianchi A, Gentilella R, Giampietro A, Desenzani P, Giustina A. Role of food intake in the modulation of hexarelin-induced growth hormone release in normal human subjects.  Horm Metab Res. 2000;  32 (4) 152-156
• 20 Bowers C Y, Reynolds G A, Durham D, Barrera C M, Pezzoli S S, Thorner M O. Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone.  J Clin Endocrinol Metab. 1990;  70 (4) 975-982
• 21 Arvat E, Maccario M, Di Vito L, Broglio F, Benso A, Gottero C, Papotti M, Muccioli G, Dieguez C, Casanueva F F, Deghenghi R, Camanni F, Ghigo E. Endocrine activities of ghrelin, a natural growth hormone secretagogue (GHS), in humans: comparison and interactions with hexarelin, a nonnatural peptidyl GHS, and GH-releasing hormone.  J Clin Endocrinol Metab. 2001;  86 (3) 1169-1174