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Horm Metab Res 2003; 35(3): 153-157
DOI: 10.1055/s-2003-39076
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Gonadotropin-Releasing Hormone Increases Melatonin Release in the Pineal Gland of the Female Rat In Vitro

M.  T.  Itoh 1 , T.  Hosaka 2 , T.  Mimuro 2 , N.  Hamada 2 , B.  Ishizuka 2
  • 1 Department of Chemistry, St. Marianna University School of Medicine, Sugao, Miyamae-ku, Kawasaki, Japan
  • 2 Department of Obstetrics and Gynecology, St. Marianna University School of Medicine, Sugao, Miyamae-ku, Kawasaki, Japan
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Publication History

Received 2 July 2002

Accepted after revision 8 October 2002

Publication Date:
07 May 2003 (online)

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Abstract

To evaluate the effect of gonadotropin-releasing hormone (GnRH) on melatonin (N-acetyl-5-methoxytryptamine) release and its synthesizing enzyme activities in pineal glands, pineals from adult female rats during diestrus were organ-cultured in a medium containing 10 -12, 10 -10, or 10 -8 M GnRH for 6 h. Melatonin release increased significantly in pineals cultured with 10 -10 and 10 -8 M GnRH compared to controls. However, in pineal glands that were organ-cultured in a medium containing 10 -12 to 10 -8 M GnRH, the activity of arylalkylamine N-acetyltransferase, which is the key regulatory enzyme in melatonin biosynthesis, showed no significant difference from controls. Likewise, GnRH at these concentrations had no significant effect on the activity of pineal hydroxyindole-O-methyltransferase, which catalyzes the final step of melatonin biosynthesis. These results show that GnRH stimulates pineal melatonin release, but suggest that GnRH does not affect its melatonin synthesis.

Key words

Melatonin - Arylalkylamine N-Acetyltransferase - Hydroxyindole-O-Methyltransferase - Gonadotropin-Releasing Hormone - Pineal Gland - Organ Culture - Female Rats

References

  • 1 Axelrod J. The pineal gland: a neurochemical transducer.  Science. 1974;  184 1341-1348
    PubMedSearch in Google Scholar
  • 2 Namboodiri M AA, Dubbels R, Klein D C. Arylalkylamine N-acetyltransferase from mammalian pineal gland.  Methods Enzymol. 1987;  142 583-590
    PubMedSearch in Google Scholar
  • 3 Sugden D, Cena V, Klein D C. Hydroxyindole-O-methyltransferase.  Methods Enzymol. 1987;  142 590-596
    PubMedSearch in Google Scholar
  • 4 Reiter R J. The melatonin rhythm: both a clock and a calendar.  Experientia. 1993;  49 654-664
    CrossrefPubMedSearch in Google Scholar
  • 5 Dollins A B, Zhdanova I V, Wurtman R J, Lynch H J, Deng M F. Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance.  Proc Natl Acad Sci USA. 1994;  91 1824-1828
    CrossrefPubMedSearch in Google Scholar
  • 6 Brezinski A. Melatonin in humans.  N Engl J Med. 1997;  336 186-195
    Search in Google Scholar
  • 7 Ying S Y, Greep Y O. Inhibition of ovulation by melatonin by the cyclic rat.  Endocrinology. 1973;  92 333-335
    PubMedSearch in Google Scholar
  • 8 Rivest R W, Lang U, Aubert M L, Sizonenko P C. Daily administration of melatonin delays rat vaginal opening and disturbs the first estrus cycles: evidence that these effects are synchronized by the onset of light.  Endocrinology. 1985;  116 779-787
    PubMedSearch in Google Scholar
  • 9 Reppert S M, Weaver D R. Forward genetic approach strikes gold: cloning of a mammalian Clock gene.  Cell. 1997;  94 83-95
    PubMedSearch in Google Scholar
  • 10 San Martin M, Bogdan A, Touitou Y. Day-night differences in the effects of gonadal hormones on melatonin release from perfused rat pineals. Evidence of a circadian control.  Steroids. 1996;  61 27-32
    CrossrefPubMedSearch in Google Scholar
  • 11 Cardinali D P, Vacas M I, Keller Sarmiento M I, Etchegoyen G S, Pereyra E N, Chuluyan H E. Neuroendocrine integrative mechanisms in pineal gland: effects of steroid and adenohypophysial hormones on melatonin synthesis in vitro.  J Steroid Biochem. 1987;  27 565-571
    CrossrefPubMedSearch in Google Scholar
  • 12 Vacas M I, Keller Sarmiento M I, Pereyra E N, Etchegoyen G S, Cardinali D P. In vitro effects of adenohypophysial hormones on rat pineal melatonin content and release.  Mol Cell Endocrinol. 1987;  50 23-27
    CrossrefPubMedSearch in Google Scholar
  • 13 Hosaka T, Mimuro T, Hamada N, Itoh M T, Ishizuka B. Stimulatory effects of LH on release of melatonin and activities of its synthesizing enzymes NAT and HIOMT in organ-cultured pineal glands of female rats.  Horm Metab Res. 2002;  34 441-445
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Haldar-Misra C, Pévet P. The influence of luteinizing hormone-releasing hormone (LHRH) on the process of protein and/or peptide secretion characterized by the formation of granular vesicles in mammalian pinealocytes. Comparative in vitro study.  Cell Tissue Res. 1983;  232 529-538
    PubMedSearch in Google Scholar
  • 15 Okatani Y, Sagara Y. Amplification of nocturnal melatonin secretion in women with functional secondary amenorrhoea: relation to endogenous oestrogen concentration.  Clin Endocrinol. 1994;  136 7-13
    PubMedSearch in Google Scholar
  • 16 Rasmussen D D. Diurnal modulation of rat hypothalamic gonadotropin-releasing hormone release by melatonin in vitro. .  J Endocrinol Invest. 1993;  16 1-7
    PubMedSearch in Google Scholar
  • 17 Messager S, Caillo M, Rossano B, Martinet L. Effect of melatonin on the release of gonadotropin-releasing hormone and cyclic AMP from the rat hypothalamus: an in vitro study.  J Neudoendocrinol. 1996;  8 801-807
    PubMedSearch in Google Scholar
  • 18 Evans J J, Janmohamed S, Forsling M L. Gonadotropin-releasing hormone and oxitocin secretion from the hypothalamus in vitro during pro-oestrus: the effects of time of day and melatonin.  Brain Res Bull. 1999;  48 93-97
    CrossrefPubMedSearch in Google Scholar
  • 19 Ishizuka B, Fusama S, Hirai K, Hosaka T, Hamada N, Amemiya A, Itoh M T. Melatonin secretion from organ-cultured pineal glands of rats: modulation by gonadectomy and gonadotropin-releasing hormone agonist administration.  Eur J Endocrinol. 2000;  142 387-392
    CrossrefPubMedSearch in Google Scholar
  • 20 Meyer M H, Masken J F, Nett T M, Niswender G D. Serum levels of gonadotropin-releasing hormone (Gn-RH) during the estrous cycle and in pentobarbital-treated rats.  Neuroendocrinology. 1974;  15 32-37
    PubMedSearch in Google Scholar
  • 21 Morris M, Knigge M. The effects of pentobarbital and ether anesthesia on hypothalamic LH-RH in the rat.  Neuroendocrinology. 1976;  20 193-200
    PubMedSearch in Google Scholar
  • 22 Itoh M T, Ishizuka B, Kuribayashi Y, Amemiya A, Sumi Y. Melatonin, its precursors, and synthesizing enzyme activities in human ovary.  Mol Hum Reprod. 1999;  5 402-408
    CrossrefPubMedSearch in Google Scholar
  • 23 Dupont A, Labrie F, Pelletier G, Puviani R, Coy D H, Coy E J, Schally A V. Organ distribution of radioactivity and disappearance of radioactivity from plasma after administration of [3H] luteinizing hormone-releasing hormone to mice and rats.  Neuroendocrinology. 1974;  16 65-73
    PubMedSearch in Google Scholar
  • 24 Piekut D T, Knigge K M. Immunohistochemical analysis of the rat pineal gland using antisera generated against analogs of luteinizing hormone-releasing hormone (LHRH).  J Histochem Cytochem. 1982;  30 106-110
    PubMedSearch in Google Scholar
  • 25 Johnson L Y, Vaughan M K, Richardson B A, Petterborg L J, Reiter R J. Variation in pineal melatonin content during the estrus cycle of the rat.  Proc Soc Exp Biol Med. 1982;  169 416-419
    PubMedSearch in Google Scholar
  • 26 Chakravarti S, Collins W P, Forecast J D, Newton J R, Oram D H, Studd J WW. Hormonal profiles after the menopause.  Br Med J. 1976;  2 784-789
    PubMedSearch in Google Scholar
  • 27 Rossmanith W G, Scherbaum W A, Lauritzen C. Gonadotropin secretion during aging in postmonopausal women.  Neuroendocrinology. 1991;  54 211-218
    PubMedSearch in Google Scholar
  • 28 Okatani Y, Morioka N, Wakatsuki A. Changes in nocturnal melatonin secretion in perimenopausal women: correlation with endogenous estrogen concentrations.  J Pineal Res. 2000;  28 111-118
    CrossrefPubMedSearch in Google Scholar
  • 29 Parker C R, Porter J C. Luteinizing hormone-releasing hormone and thyrotropin-releasing hormone in the hypothalamus of women: effects of age and reproductive status.  J Clin Endocrinol Metab. 1984;  58 488-491
    PubMedSearch in Google Scholar
  • 30 Beitins I Z, Barkan A, Klibanski A, Kyung N, Reppert S M, Badger T M, Veldhuis J, McArthur J W. Hormonal responses to short term fasting in postmenopausal women.  J Clin Endocrinol Metab. 1985;  60 1120-1126
    PubMedSearch in Google Scholar
  • 31 Kadva A, Djahanbakhch O, Monson J, Di W L, Silman R. Elevated nocturnal melatonin is a consequence of gonadotropin-releasing hormone deficiency in women with hypothalamic amenorrhea.  J Clin Endocrinol Metab. 1998;  83 3653-3662
    CrossrefPubMedSearch in Google Scholar
  • 32 Givalois S LL, Pelletier G. Effects of aging and melatonin administration on gonadotropin-releasing hormones (GnRH) gene expression in the male and female rat.  Peptides. 1997;  7 1023-1028
    PubMedSearch in Google Scholar

M. T. Itoh, Ph. D.

Department of Chemistry · St. Marianna University School of Medicine

Sugao · Miyamae-ku · Kawasaki 216-8511 · Japan

Phone: +81 (44) 977-8111 ext. 4517

Fax: + 81 (44) 977-8133

Email: itohmt@marianna-u.ac.jp