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

Abstract

The pineal hormone melatonin (N-acetyl-5-methoxytryptamine) exerts antigonadotropic effects in some mammalian species. To evaluate the effect of luteinizing hormone (LH) on melatonin release and its synthesizing enzyme activities in pineal glands, pineals of adult female rats undergoing diestrus were organ-cultured in a medium containing 10^-12, 10^-10 or 10^-8 M LH for 6 h. Melatonin release increased significantly in pineals cultured with 10^-12 and 10^-10 M LH, as compared to control values. Similarly, the activity of arylalkylamine N-acetyltransferase (NAT), the key regulatory enzyme in melatonin biosynthesis, was significantly higher in pineals cultured with 10^-12 and 10^-10 M LH for 6 h, while LH at 10^-8 M had no effect. Although LH at 10^-10 M increased pineal hydroxyindole-O-methyltransferase (HIOMT) activity, which catalyzes the final step of melatonin biosynthesis, LH at 10^-12 and 10^-8 M had no effect. These results demonstrate that at relatively low physiological levels, LH stimulates pineal melatonin synthesis and release, mainly by increasing NAT activity.

Key words

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

References

• 1 Axelrod J. The pineal gland: A neurochemical transducer.  Science. 1974;  184 1341-1348
• 2 Namboodiri M AA, Dubbels R, Klein D C. Arylalkylamine N-acetyltransferase from mammalian pineal gland.  Methods Enzymol. 1987;  142 583-590
• 3 Sugden D, Cena V, Klein D C. Hydroxyindole-O-methyltransferase.  Methods Enzymol. 1987;  142 590-596
• 4 Reiter R J. The melatonin rhythm: Both, a clock and a calendar.  Experientia. 1993;  49 654-664
• 5 Dollins A B, Zhdanova I V, Wurtman R J, Lynch H J, Deng M H. 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
• 6 Brezinski A. Melatonin in humans.  N Eng J Med. 1997;  336 186-195
• 7 Ying S Y, Greep R O. Inhibition of ovulation by melatonin by the cyclic rat.  Endocrinology. 1973;  92 333-335
• 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
• 9 Reppert S M, Weaver D R. Forward genetic approach strikes gold: Cloning of a mammalian Clock gene.  Cell. 1997;  94 83-95
• 10 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
• 11 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
• 12 San Martin M, Bogdan A, Touitou Y. Day-night differences in the effects of gonadal hormones on melatonin release from perifused rat pineals: Evidence of a circadian control.  Steroids. 1996;  61 27-32
• 13 Butcher R L, Collins W E, Fugo N W. Plasma concentration of LH, FSH, prolactin, progesterone and estradiol-17β throughout the 4-day estrus cycle of the rat.  Endocrinology. 1974;  94 1704-1708
• 14 Fox S R, Smith M S. Changes in the pulsatile pattern of luteinizing hormone secretion during the rat estrous cycle.  Endocrinology. 1985;  116 1485-1492
• 15 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
• 16 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
• 17 Karasek M, Marek K, Kunert-Radek J. Ultrastructure of rat pinealocytes in vitro: Influence of gonadotropic hormones and LH-RH.  Cell Tissue Res. 1978;  195 547-556
• 18 Karasek M. Ultrastructure of rat pineal gland in organ culture: Influence of norepinephrine, dibutyryl cyclic adenosine 3′, 5′-mosophosphate and adnophysis.  Endocrinologie. 1974;  64 106-114
• 19 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
• 20 Wurtman R J, Axelrod J, Snyder S H, Chu E W. Changes in the enzymatic synthesis of melatonin in the pineal during the estrous cycle.  Endocrinology. 1965;  76 798-800
• 21 Wallen E P, Yochim J M. Rhythmic function of pineal hydroxyindole-O-methyltransferase during the estrus cycle: An analysis.  Biol Reprod. 1974;  10 461-466
• 22 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
• 23 Martin J E, Sattler C. Developmental loss of the acute inhibitory effect of melatonin on the in vitro pituitary luteinizing hormone and follicle-stimulating hormone responses to luteinizing hormone-releasing hormone.  Endocrinology. 1979;  105 1007-1012
• 24 Diaz E, Fernandez C, Castrillon P O, Esquino A I, Marin B, Diaz Lopez B. Effect of exogenous melatonin on neuroendocrine-reproductive function of middle-aged female rats.  J Reprod Fertil. 1999;  117 331-337
• 25 Evans J J, Janmohamed S, Forsling M L. Gonadotropin-releasing hormone and oxytocin secretion from the hypothalamus in vitro during pro-oestrus: The effect of time of day and melatonin.  Brain Res Bull. 1999;  48 93-97
• 26 Walker R F, McCamant S, Timiras P S. Melatonin and the influence of the pineal gland on timing of the LH surge in rats.  Neuroendocrinology. 1982;  35 37-42