Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-10T19:57:33.758Z Has data issue: false hasContentIssue false
  • English
  • Français

Expression of melatonin (MT1, MT2) and melatonin-related receptors in the adult rat testes and during development

Published online by Cambridge University Press:  29 January 2010

Gaia Izzo ,
Aniello Francesco ,
Diana Ferrara ,
Maria Rosaria Campitiello ,
Ismene Serino ,
Sergio Minucci  and
Michela d'Istria
Gaia Izzo
Affiliation:
Dipartimento di Medicina Sperimentale-Sezione di Fisiologia Umana e Funzioni Biologiche Integrate ‘F. Bottazzi’, Seconda Università degli Studi di Napoli, via Costantinopoli 16, 80138 Napoli, Italy.
Aniello Francesco
Affiliation:
Dipartimento di Biologia Strutturale e Funzionale. Università di Napoli ‘Federico II’, via Cinthia, Napoli, Italy.
Diana Ferrara
Affiliation:
Dipartimento di Medicina Sperimentale-Sezione di Fisiologia Umana e Funzioni Biologiche Integrate ‘F. Bottazzi’, Seconda Università degli Studi di Napoli, via Costantinopoli 16, 80138 Napoli, Italy.
Maria Rosaria Campitiello
Affiliation:
Dipartimento Materno Infantile. Seconda Università degli Studi di Napoli, via Costantinopoli 16, 80138 Napoli, Italy.
Ismene Serino
Affiliation:
Dipartimento di Medicina Sperimentale-Sezione di Fisiologia Umana e Funzioni Biologiche Integrate ‘F. Bottazzi’, Seconda Università degli Studi di Napoli, via Costantinopoli 16, 80138 Napoli, Italy.
Sergio Minucci*
Affiliation:
Dipartimento di Medicina Sperimentale-Sezione di Fisiologia Umana e Funzioni Biologiche Integrate ‘F. Bottazzi’, Seconda Università degli Studi di Napoli, via Costantinopoli 16, 80138 Napoli, Italy.
Michela d'Istria
Affiliation:
Dipartimento di Medicina Sperimentale-Sezione di Fisiologia Umana e Funzioni Biologiche Integrate ‘F. Bottazzi’, Seconda Università degli Studi di Napoli, via Costantinopoli 16, 80138 Napoli, Italy.
*
All correspondence to: Sergio Minucci. Dipartimento di Medicina Sperimentale-Sezione di Fisiologia Umana e Funzioni Biologiche Integrate ‘F. Bottazzi’, Seconda Università degli Studi di Napoli, via Costantinopoli 16, 80138 Napoli, Italy. Tel: +39 815665829. Fax: +39 815667500. e-mail: sergio.minucci@unina2.it
Get access Rights & Permissions [Opens in a new window]

Summary

It is well known that melatonin provokes reproductive alterations in response to changes in hours of daylight in seasonally breeding mammals, exerting a regulatory role at different levels of the hypothalamic–pituitary–gonadal axis. Although it has also been demonstrated that melatonin may affect testicular activity in vertebrates, until now, very few data support the hypothesis of a local action of melatonin in the male gonads. The aim of this study was to investigate whether MT1, MT2 melatonin receptors and the H9 melatonin-related receptor, are expressed in the adult rat testes and during development. A semi-quantitative RT-PCR method was used to analyse the expression of MT1, MT2 and H9 receptors mRNAs in several rat tissues, mainly focusing on testes during development and adult life. Our results provide molecular evidences of the presence of both MT1 and, for the first time, MT2 melatonin receptors as well as of the H9 melatonin-related receptor in the examined tissues, including adult testes. During development MT1 and MT2 transcripts are expressed at lower levels in testes of rats from 1 day to 1 week of age, lightly increased at 2 weeks of age and remained permanently expressed throughout development until 6 months. These data strongly support the hypothesis that melatonin acts directly in male vertebrate gonads suggesting that rat testes may be a suitable model to verify the role of indolamine in vertebrate testicular activity.

Keywords

DevelopmentMelatonin receptorsRatReproductionTestes
Type
Research Article
Information
Zygote , Volume 18 , Issue 3 , August 2010 , pp. 257 - 264
Copyright
Copyright © Cambridge University Press 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aleandri, V., Spina, V. & Morini, A. (1996). The pineal gland and reproduction. Hum. Reprod. Update 2, 225–35.CrossRefGoogle ScholarPubMed
Anton-Tay, F., Chou, C., Anton, S. & Wurtman, R.J. (1968). Brain serotonin concentration: elevation following intraperitoneal administration of melatonin. Science 162, 277–8.CrossRefGoogle ScholarPubMed
Arendt, J. (1986). Role of the pineal gland and melatonin in seasonal reproductive function in mammals. Oxf. Rev. Reprod. Biol. 8, 266–320.Google ScholarPubMed
Bartness, T.J., Powers, J.B., Hastings, M.H., Bittman, E.L. & Goldman, B.D. (1993). The timed infusion paradigm for melatonin delivery: what has it taught us about the melatonin signal, its reception and the photoperiodic control of seasonal responses? J. Pineal Res. 15, 161–90.CrossRefGoogle ScholarPubMed
Bittman, E.L., Kaynard, A.H., Olster, D.H., Robinson, J.E., Yellon, S.M. & Karsch, F.J. (1985). Pineal melatonin mediates photoperiodic control of pulsatile luteinizing hormone secretion in the ewe. Neuroendocrinology 40, 409–18.CrossRefGoogle ScholarPubMed
Cardinali, D.P., Vacas, M.I. & Boyer, E.E. (1979). Specific binding of melatonin in bovine brain. Endocrinology 105, 437–41.CrossRefGoogle ScholarPubMed
Cassone, V.M., Warren, W.S., Brooks, D.S. & Lu, J. (1993). Melatonin, the pineal gland and circadian rhythms. J. Biol. Rhythms Suppl. S73–S81.Google Scholar
Chomczynski, P. & Sacchi, N. (1987). Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Anal. Biochem. 162, 156–9.CrossRefGoogle ScholarPubMed
Clemens, J.W., Jarzynka, M.J. & Witt-Enderby, P.A. (2001). Down-regulation of mt1 melatonin receptors in rat ovary following estrogen exposure. Life Sci. 69, 27–35.CrossRefGoogle ScholarPubMed
d'Istria, M., Palmiero, C., Serino, I., Izzo, G. & Minucci, S. (2003). Inhibition of the basal and oestradiol-stimulated mitotic activity of primary spermatogonia by melatonin in the testes of frog, Rana esculenta, in vivo and in vitro. Reproduction 126, 83–90.CrossRefGoogle ScholarPubMed
d'Istria, M., Serino, I., Izzo, G., Ferrara, D., De Rienzo, G. & Minucci, S. (2004). Effects of melatonin treatment on Leydig cell activity in the testes of the frog Rana esculenta. Zygote 12, 293–9.CrossRefGoogle ScholarPubMed
Diaz, B., Diaz, E., Colmenero, M.F., Arce, A., Esquifino, A. & Marìn, B. (1999). Maternal melatonin influences rates of somatic and reproductive organs postnatal development of male rat offspring. Neuro. Endocrinol. Lett. 20, 69–76.Google ScholarPubMed
Drew, J.E., Barrett, P., Mercer, J.G. et al. (2001). Localization of the melatonin-related receptor in the rodent brain and peripheral tissues. J. Neuroendocrinol. 13, 453–8.CrossRefGoogle ScholarPubMed
Dubocovich, M.L., Masana, M.I., Iacob, S. & Sauri, D.M. (1997). Melatonin receptor antagonists that differentiate between the human Mel1a and Mel1b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor. Naunyn Schmiedebergs Arch. Pharmacol. 355, 365–75.CrossRefGoogle ScholarPubMed
Duncan, M.J., Takahashi, J.S. & Dubocovich, M.L. (1988). 2-[125I]iodomelatonin binding sites in hamster brain membranes: pharmacological characteristics and regional distribution. Endocrinology 122, 1825–33.CrossRefGoogle ScholarPubMed
Frungieri, M.B., Mayerhofer, A., Zitta, K., Pignataro, O.P., Calandra, R.S. & Gonzalez-Calvar, S.I. (2005). Direct effect of melatonin on Syrian hamster testes: melatonin subtype 1a receptors, inhibition of androgen production and interaction with the local corticotropin-releasing hormone system. Endocrinology 146, 1541–52.CrossRefGoogle ScholarPubMed
Fu, Z., Kato, H., Kotera, N., Noguchi, T., Sugahara, K. & Kubo, T. (2001). Regulation of hydroxyindole-O-methyltransferase gene expression in Japanese quail (Coturnix coturnix japonica). Biosci. Biotechnol. Biochem. 65, 2504–11.CrossRefGoogle ScholarPubMed
Gubitz, A.K. & Reppert, S.M. (1999). Assignment of the melatonin-related receptor to human chromosome X (GPR50) and mouse chromosome X (Gpr50). Genomics 55, 248–51.CrossRefGoogle ScholarPubMed
Hazlerigg, D.G., Morgan, P.J. & Messager, S. (2001). Decoding photoperiodic time and melatonin in mammals: what can we learn from the pars tuberalis? J. Biol. Rhythms 16, 326–35.CrossRefGoogle ScholarPubMed
Izzo, G., d'Istria, M., Serino, I. & Minucci, S. (2004). Inhibition of the increase 17β-estradiol-induced mast cell number by melatonin in the testes of the frog Rana esculenta, in vivo and in vitro. J. Exp. Biol. 207, 437–41.CrossRefGoogle ScholarPubMed
Kato, H., Fu, Z., Kotera, N., Sugahara, K. & Kubo, T. (1999). Regulation of the expression of serotonin N-acetyltransferase gene in Japanese quail (Coturnix japonica): I. Rhythmic pattern and effect of light. J. Pineal Res. 27, 24–33.CrossRefGoogle ScholarPubMed
Kus, I., Sarsilmaz, M., Ogetürk, M., Yilmaz, B., Keleştimur, H. & Oner, H. (2000). Ultrastructural interrelationship between the pineal gland and the testes in the male rat. Arch. Androl. 45, 119–24.Google ScholarPubMed
Kuş, I., Akpolat, N., Ozen, O.A., Songur, A., Kavakli, A. & Sarsilmaz, M. (2002). Effects of melatonin on Leydig cells in pinealectomized rat: an immunohistochemical study. Acta Histochem. 104, 93–7.CrossRefGoogle ScholarPubMed
Morgan, P.J., Barrett, P., Howell, H.E. & Helliwell, R. (1994). Melatonin receptors: localization, molecular pharmacology and physiological significance. Neurochem. Int. 24, 101–46.CrossRefGoogle ScholarPubMed
Niedziela, M., Lerchl, A. & Nieschlag, E. (1995). Direct effects of the pineal hormone melatonin on testosterone synthesis of Leydig cells in Djungarian hamsters (Phodopus sungorus) in vitro. Neurosci. Lett. 201, 247–50.CrossRefGoogle ScholarPubMed
Olivares, A.N., Valladares, L.E., Bustos-Obregón, E. & Núñez, S.M. (1989). Testicular function of sexually immature rats chronically treated with melatonin. Arch. Biol. Med. Exp. 22, 387–93.Google ScholarPubMed
Pandi-Perumal, S.R., Trakht, I., Srinivasan, V., et al. (2008). Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog. Neurobiol. 853, 335–53.CrossRefGoogle Scholar
Paul, P., Lahaye, C., Delagrange, P., Nicolas, J.P., Canet, E. & Boutin, J.A. (1999). Characterization of 2-[125I]iodomelatonin binding sites in Syrian hamster peripheral organs. J. Pharmacol. Exp. Ther. 290, 334–40.Google ScholarPubMed
Pickering, D.S. & Niles, L.P. (1990). Pharmacological characterization of melatonin binding sites in Syrian hamster hypothalamus. Eur. J. Pharmacol. 175, 71–7.CrossRefGoogle ScholarPubMed
Redins, C.A., Redins, G.M. & Novaes, J.C. (2002). The effects of treatment with melatonin on the ultrastructure of mouse Leydig cells: a quantitative study. Braz. J. Biol. 62, 517–23.CrossRefGoogle ScholarPubMed
Reiter, R.J. (1980). Photoperiod: its importance as an impeller of pineal and seasonal reproductive rhythms. Int. J. Biometeorol. 24, 57–63.CrossRefGoogle ScholarPubMed
Reiter, R.J. (1981). Pineal control of reproduction. Prog. Clin. Biol. Res. 59, 349–355.Google Scholar
Reiter, R.J. (1991a). Melatonin: the chemical expression of darkness. Mol. Cell Endocrinol. 79, 153–8.CrossRefGoogle ScholarPubMed
Reiter, R.J. (1991b). Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr. Rev. 12, 151–80.CrossRefGoogle ScholarPubMed
Reiter, R.J. (1991c). Neuroendocrine effects of light. Int. J. Biometeorol. 35, 169–75.CrossRefGoogle ScholarPubMed
Reiter, R.J. (1993). The melatonin rhythm: both a clock and a calendar. Experientia 49, 654–64.CrossRefGoogle Scholar
Reppert, S.M., Godson, C., Mahle, C.D., Weaver, D.R., Slaugenhaupt, S.A. & Gusella, J.F. (1995). Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proc. Natl. Acad. Sci. USA 92, 8734–8.CrossRefGoogle ScholarPubMed
Reppert, S.M., Weaver, D.R., Ebisawa, T., Mahle, C.D. & Kolakowski, L.F. Jr (1996). Cloning of a melatonin-related receptor from human pituitary. FEBS Lett. 386, 219–24.CrossRefGoogle ScholarPubMed
Sallinen, P., Saarela, S., Ilves, M., Vakkuri, O. & Leppäluoto, J. (2005). The expression of MT1 and MT2 melatonin receptor mRNA in several rat tissues. Life Sci. 76, 1123–34.CrossRefGoogle ScholarPubMed
Sanger, F., Donelson, J.E., Coulson, A.R., Kössel, H. & Fischer, D. (1974). Determination of a nucleotide sequence in bacteriophage f1 DNA by primed synthesis with DNA polymerase. J. Mol. Biol. 90, 315–33.CrossRefGoogle ScholarPubMed
Shiu, S.Y., Li, L., Siu, S.W., Xi, S.C., Fong, S.W. & Pang, S.F. (2000). Biological basis and possible physiological implications of melatonin receptor-mediated signaling in the rat epididymis. Biol. Signals Recept. 9, 172–87.CrossRefGoogle ScholarPubMed
Stankov, B. & Reiter, R.J. (1990). Melatonin receptors: current status, facts and hypotheses. Life Sci. 46, 971–82.CrossRefGoogle Scholar
Stefulj, J., Hörtner, M., Ghosh, M., et al. (2001). Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat. J. Pineal Res. 30, 243–7.CrossRefGoogle ScholarPubMed
Tijmes, M., Pedraza, R. & Valladares, L. (1996). Melatonin in the rat testes: evidence for local synthesis. Steroids 61, 65–8.CrossRefGoogle ScholarPubMed
Valenti, S., Guido, R., Giusti, M. & Giordano, G. (1995). In vitro acute and prolonged effects of melatonin on purified rat Leydig cell steroidogenesis and adenosine 3′,5′-monophosphate production. Endocrinology 136, 5357–62.CrossRefGoogle ScholarPubMed
Valenti, S., Giusti, M., Guido, R. & Giordano, G. (1997). Melatonin receptors are present in adult rat Leydig cells and are coupled through a pertussis toxin-sensitive G-protein. Eur. J. Endocrinol. 136, 633–9.CrossRefGoogle ScholarPubMed
Valenti, S., Thellung, S., Florio, T., Giusti, M., Schettini, G. & Giordano, G. (1999). A novel mechanism for the melatonin inhibition of testosterone secretion by rat Leydig cells: reduction of GnRH-induced increase in cytosolic Ca2+. J. Mol. Endocrinol. 23, 299–306.CrossRefGoogle ScholarPubMed
Valenti, S., Fazzuoli, L., Giordano, G. & Giusti, M. (2001). Changes in binding of iodomelatonin to membranes of Leydig cells and steroidogenesis after prolonged in vitro exposure to melatonin. Int. J. Androl. 24, 80–6.CrossRefGoogle ScholarPubMed
Vanecek, J. & Watanabe, K. (1998). Melatonin inhibits the increase of cyclic AMP in rat suprachiasmatic neurons induced by vasoactive intestinal peptide. Neurosci. Lett. 252, 21–4.CrossRefGoogle ScholarPubMed
Vera, H., Tijmes, M. & Valladares, L.E. (1997). Melatonin and testicular function: characterization of binding sites for 2-[125I]-iodomelatonin in immature rat testes. Steroids 62, 226–9.CrossRefGoogle ScholarPubMed
Weaver, D.R. (1999). The roles of melatonin in development. Adv. Exp. Med. Biol. 460, 199–214.CrossRefGoogle ScholarPubMed
Wiechmann, A.F., Campbell, L.D. & Defoe, D.M. (1999). Melatonin receptor RNA expression in Xenopus retina. Brain Res. Mol. Brain Res. 63, 297–303.CrossRefGoogle ScholarPubMed
Wu, C.C., Chiao, C.W., Hsiao, G., Chen, A. & Yen, M.H. (2001). Melatonin prevents endotoxin-induced circulatory failure in rats. J. Pineal Res. 30, 147–56.CrossRefGoogle ScholarPubMed
Wurtman, R.J. & Axelrod, J. (1966). The physiologic effects of melatonin and the control of its biosynthesis. Probl. Actuels Endocrinol. Nutr. 10, 189–200.Google ScholarPubMed