Download PDF
Horm Metab Res 2004; 36(2): 86-91
DOI: 10.1055/s-2004-814216
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Induction of Growth Hormone Release by Pueraria thunbergiana BENTH.

D.  Y.  Jung1 , H.  Ha1 , C.  Kim1
  • 1Drug Research and Development Team, Korea Institute of Oriental Medicine, Seoul, Korea
Further Information

Publication History

Received 8 October 2002

Accepted after revision 19 August 2003

Publication Date:
05 March 2004 (online)

Also available at
    Permissions and Reprints

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 Tmax value for rGH after injection of 20 µg/kg of rGHRH was 10 - 30 min, while the Cmax value was increased by approximately 12-fold compared to the control group (198.2 ± 25.0 pM) and the AUC0 - 45 was increased to 10 times the level of the control group (10,840.9 ± 845.5 min. pM). On the other hand, Tmax for the HPS was 60 min, while Cmax was increased approximately to 5.8 fold compared to control (244.1 ± 36.4 pM). Cmax 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.

Key words

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
    PubMedGoogle Scholar
  • 2 Kim C, Ha H, Kim H, Lee J H, Song K Y. Pueraria lobata OHWL. as an Osteoporosis therapeutics.  Korean J Food Sci Technol. 2002;  34 (4) 710-718
    PubMedGoogle Scholar
  • 3 Finch C E, Tanzi R E. Genetics of aging.  Science. 1997;  278 (5337) 407-411
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 7 Argente J, Pozo J, Chowen J A. The growth hormone axis: control and effects.  Horm Res. 1996;  45 (Suppl 1) 9-11
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    Google Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar

C. Kim, Ph. D. 

Drug Research and Development Team · Korea Institute of Oriental Medicine ·

129-11 Chungdam-dong, Kangnam-ku · Seoul, 135-100 · Korea

Phone: + 82 (2) 3442-1994-223, + 82 (2) 3442-2120

Fax: + 82 (2) 3442-0220, + 82 (2) 3442-1030

Email: skim@kiom.re.kr

      >