Artículo

Rossi, S.P.; Matzkin, M.E.; Terradas, C.; Ponzio, R.; Puigdomenech, E.; Levalle, O.; Calandra, R.S.; Frungieri, M.B. "New insights into melatonin/CRH signaling in hamster Leydig cells" (2012) General and Comparative Endocrinology. 178(1):153-163
Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

We have previously described that melatonin inhibits androgen production in hamster testes via melatonin subtype 1a (mel1a) receptors and the local corticotrophin-releasing hormone (CRH) system. This study attempted to determine the initial events of the melatonin/CRH signaling pathway. In Leydig cells from reproductively active Syrian hamsters, Western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and a colorimetric assay demonstrated that melatonin and CRH activate tyrosine phosphatases and subsequently reduce the phosphorylation levels of extracellular signal-regulated kinase (erk) and c-jun N-terminal kinase (jnk), down-regulate the expression of c-jun, c-fos and steroidogenic acute regulatory (StAR), and inhibit the production of testosterone. These effects were prevented by a highly selective CRH antagonist, thus indicating that melatonin does not exert a direct role. Specific mitogen-activated protein kinase kinase (MEK) and jnk blockers inhibited expression of c-jun, c-fos, StAR and the production of testosterone, confirming that these are events triggered downstream of erk and jnk. In Leydig cells from photoperiodically regressed adult hamsters, CRH inhibited the production of androstane-3α,17β-diol (3α-diol), the main androgen produced, through the same signaling pathway. Testicular melatonin concentration was 3-4-fold higher in reproductively inactive hamsters than that detected in active animals. Since melatonin, CRH, and their receptors are present not only in hamster testes but also in testicular biopsies of infertile men, we can conjecture about the relevance of this previously uncharacterized pathway in human fertility disorders. In summary, our study identifies crucial intracellular events triggered by melatonin/CRH in the testis that lead to a down-regulation of the steroidogenic process. © 2012 Elsevier Inc.

Registro:

Documento: Artículo
Título:New insights into melatonin/CRH signaling in hamster Leydig cells
Autor:Rossi, S.P.; Matzkin, M.E.; Terradas, C.; Ponzio, R.; Puigdomenech, E.; Levalle, O.; Calandra, R.S.; Frungieri, M.B.
Filiación:Laboratorio de Esteroides, Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 1121 Buenos Aires, Argentina
División de Endocrinología, Hospital Durand, Facultad de Medicina, Universidad de Buenos Aires, Díaz Vélez 5044, 1405 Buenos Aires, Argentina
Instituto Médico PREFER, Facultad de Medicina, Universidad de Buenos Aires, Güemes 2348, 1650 San Martín, Provincia de Buenos Aires, Argentina
Instituto de Investigaciones en Reproducción, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 1121 Buenos Aires, Argentina
Palabras clave:Androgens; CRH; Hamster; Leydig cells; MAP kinases; Melatonin; Transcription factors; Tyrosine phosphatases; androstanediol; corticotropin releasing factor; corticotropin releasing factor receptor; melatonin; melatonin 1 receptor; melatonin receptor; mitogen activated protein kinase; protein c fos; protein c jun; protein tyrosine phosphatase; steroidogenic acute regulatory protein; stress activated protein kinase; testosterone; adult animal; androgen synthesis; animal cell; animal tissue; article; colorimetry; controlled study; down regulation; enzyme activation; enzyme phosphorylation; hormone inhibition; human; human tissue; Leydig cell; male; male infertility; nonhuman; priority journal; protein expression; reverse transcription polymerase chain reaction; signal transduction; steroidogenesis; Syrian hamster; testis biopsy; Western blotting
Año:2012
Volumen:178
Número:1
Página de inicio:153
Página de fin:163
DOI: http://dx.doi.org/10.1016/j.ygcen.2012.04.031
Título revista:General and Comparative Endocrinology
Título revista abreviado:Gen. Comp. Endocrinol.
ISSN:00166480
CODEN:GCENA
CAS:androstanediol, 1852-53-5, 25126-76-5, 67332-38-1; corticotropin releasing factor, 9015-71-8, 178359-01-8, 79804-71-0, 86297-72-5, 86784-80-7; melatonin, 73-31-4; mitogen activated protein kinase, 142243-02-5; protein tyrosine phosphatase, 79747-53-8, 97162-86-2; steroidogenic acute regulatory protein, 168183-61-7; stress activated protein kinase, 155215-87-5; testosterone, 58-22-0
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00166480_v178_n1_p153_Rossi

Referencias:

  • Arendt, J., Melatonin (1988) Clin. Endocrinol. (Oxf.), 29, pp. 205-229
  • Barrett, P., Choi, W.S., Morris, M., Morgan, P., A role for tyrosine phosphorylation in the regulation and sensitization of adenylate cyclase by melatonin (2000) FASEB J., 14, pp. 1619-1628
  • Bartke, A., Male hamster reproductive endocrinology (1985) The Hamster, pp. 73-98. , Plenum Press, New York, H.I. Siegel (Ed.)
  • Basta-Kaim, A., Budziszewska, B., Jaworska-Feil, L., Tetich, M., Kubera, M., LeŚkiewicz, M., Otczyk, M., Lasoń, W., Antipsychotic drugs inhibit the human corticotropin-releasing-hormone gene promoter activity in neuro-2A cells-an involvement of protein kinases (2006) Neuropsychopharmacology, 31, pp. 853-865
  • Bonfiglio, J.J., Inda, C., Refojo, D., Holsboer, F., Arzt, E., Silberstein, S., The corticotropin-releasing hormone network and the hypothalamic-pituitary-adrenal axis: molecular and cellular mechanisms evolved (2011) Neuroendocrinology, 94, pp. 12-20
  • Cao, J., Cetrulo, C.L., Theoharides, T.C., Corticotropin-releasing hormone induces vascular endothelial growth factor release from human mast cells via the cAMP/protein kinase A/p38 mitogen-activated protein kinase pathway (2006) Mol. Pharmacol., 69, pp. 998-1006
  • Cardinali, D.P., Lynch, H.J., Wurtman, R.J., Binding of melatonin to human and rat plasma proteins (1972) Endocrinology, 91, pp. 1213-1218
  • Cui, P., Yu, M., Luo, Z., Dai, M., Han, J., Xiu, R., Yang, Z., Intracellular signaling pathways involved in cell growth inhibition of human umbilical vein endothelial cells by melatonin (2008) J. Pineal Res., 44, pp. 107-114
  • Das, A., McDowell, M., Pava, M.J., Smith, J.A., Reiter, R.J., Woodward, J.J., Varma, A.K., Banik, N.L., The inhibition of apoptosis by melatonin in VSC4.1 motoneurons exposed to oxidative stress, glutamate excitotoxicity, or TNF-alpha toxicity involves membrane melatonin receptors (2010) J. Pineal Res., 48, pp. 157-169
  • Del Castillo, E.B., Trabucco, A., de la Balze, F.A., Syndrome produced by absence of the germinal epithelium without impairment of the Sertoli or Leydig cells (1947) J. Clin. Endocrinol. Metabol., 7, pp. 493-502
  • Dufau, M.L., Tinajero, J.C., Fabbri, A., Corticotropin-releasing factor: an antireproductive hormone of the testis (1993) FASEB J., 7, pp. 299-307
  • Elliott-Hunt, C.R., Kazlauskaite, J., Wilde, G.J., Grammatopoulos, D.K., Hillhouse, E.W., Potential signalling pathways underlying corticotrophin-releasing hormone-mediated neuroprotection from excitotoxicity in rat hippocampus (2002) J. Neurochem., 80, pp. 416-425
  • Esposito, E., Genovese, T., Caminiti, R., Bramanti, P., Meli, R., Cuzzocrea, S., Melatonin reduces stress-activated/mitogen-activated protein kinases in spinal cord injury (2009) J. Pineal Res., 46, pp. 79-86
  • Frungieri, M.B., Mayerhofer, A., Zitta, K., Pignataro, O.P., Calandra, R.S., Gonzalez-Calvar, S.I., Direct effect of melatonin on syrian hamster testes: Mel1a receptors, inhibition of androgen production, and interaction with the local corticotropin-releasing hormone (CRH) system (2005) Endocrinology, 146, pp. 1541-1552
  • Frungieri, M.B., Weidinger, S., Meineke, V., Kohn, F.M., Mayerhofer, A., Proliferative action of mast cell tryptase is mediated by PAR2, COX2, prostaglandins and PPARγ: possible relevance to human fibrotic disorders (2002) Proc. Natl. Acad. Sci. USA, 99, pp. 15072-15077
  • Frungieri, M.B., Gonzalez-Calvar, S.I., Bartke, A., Calandra, R.S., Influence of age and photoperiod on steroidogenic function of the testis in the golden hamster (1999) Int. J. Androl., 22, pp. 243-252
  • Frungieri, M.B., Gonzalez-Calvar, S.I., Parborell, F., Albrecht, M., Mayerhofer, A., Calandra, R.S., Cyclooxygenase-2 (COX-2) and prostaglandin F2α (PGF2α) in Syrian hamster leydig cells: inhibitory role on LH/hCG-stimulated testosterone production (2006) Endocrinology, 147, pp. 4476-4485
  • Frungieri, M.B., Gonzalez-Calvar, S.I., Calandra, R.S., Polyamine levels in testes and seminal vesicles from adult golden hamsters during gonadal regression-recrudescence (1996) J. Androl., 17, pp. 683-691
  • Fu, Z., Kato, H., Kotera, N., Noguchi, T., Sugahara, K., Kubo, T., Regulation of hydroxyindole-O-methyltransferase gene expression in Japanese quail (Coturnix japonica) (2001) Biosci. Biotechnol. Biochem., 65, pp. 2504-2511
  • Gee, C.E., Mansuy, I.M., Protein phosphatases and their potential implications in neuroprotective processes (2005) Cell Mol. Life Sci., 62, pp. 1120-1130
  • Gunduz, B., Daily rhythm in serum melatonin and leptin levels in the Syrian hamster (2002) Comp. Biochem. Physiol. A. Mol. Integr. Physiol., 132, pp. 393-401
  • Hall, S.H., Berthelon, M.C., Avallet, O., Saez, J.M., Regulation of c-fos, c-jun, jun-B, and c-myc messenger ribonucleic acids by gonadotropin and growth factors in cultured pig Leydig cell (1991) Endocrinology, 129, pp. 1243-1249
  • Harumi, T., Pandi-Perumal, S.R., Martinez, G.R., Di Mascio, P., Hayashi, Y., Chromatographic analyses of biogenic melatonin and its related indolamines (2007) Melatonin from Molecules to Therapy, pp. 3-22. , Nova Science Publishers Inc., New York, S.R. Pandi-Perumal, D.P. Cardinali (Eds.)
  • Hoffman, K., The influence of photoperiod and melatonin on testis size, body weight and pelage color in the Djungarian hamster (Phodopus sungorus) (1973) J. Comp. Physiol., 85, pp. 267-282
  • Kageyama, K., Hanada, K., Moriyama, T., Imaizumi, T., Satoh, K., Suda, T., Differential regulation of CREB and ERK phosphorylation through corticotropin-releasing factor receptors type 1 and 2 in AtT-20 and A7r5 cells (2007) Mol. Cell. Endocrinol., 263, pp. 90-102
  • Kageyama, K., Suda, T., Regulatory mechanisms underlying corticotrophin-releasing factor gene expression in the hypothalamus (2009) Endocr. J., 56, pp. 335-344
  • Kato, H., Fu, Z., Kotera, N., Sugahara, K., Kubo, T., Regulation of the expression of serotonin N-acetyltransferase gene in Japanese quail (Coturnix japonica): I. Rhythmic pattern and effect of light (1999) J. Pineal Res., 27, pp. 24-33
  • Kim, E.K., Choi, E.J., Pathological roles of MAPK signaling pathways in human diseases (1802) Biochim. Biophys. Acta, 2010, pp. 396-405
  • Kimball, S.R., Abbas, A., Jefferson, L.S., Melatonin represses oxidative stress-induced activation of the MAP kinase and mTOR signaling pathways in H4IIE hepatoma cells through inhibition of Ras (2008) J. Pineal Res., 44, pp. 379-386
  • Lenassi, M., Plemenitaš, A., The role of p38 MAP kinase in cancer cell apoptosis (2006) Radiol. Oncol., 40, pp. 51-56
  • Levy, H., Deane, H.W., Rubin, B.L., Visualization of steroid 3ß-ol-dehydrogenase activity in tissues of intact and hypophysectomized rats (1959) Endocrinology, 65, pp. 932-943
  • Li, H., Robinson, P.J., Kawashima, S., Funder, J.W., Liu, J.-P., Differential regulation of MAP kinase activity by corticotropin-releasing hormone in normal and neoplastic corticotropes (1998) Int. J. Biochem. Cell. Biol., 30, pp. 1389-1401
  • Lincoln, G.A., Neuroendocrine regulation of seasonal gonadotrophin and prolactin rhythms: lessons from the Soay ram model (2002) Reprod. Suppl., 59, pp. 131-147
  • Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., Protein measurement with the Folin phenol reagent (1951) J. Biol. Chem., 193, pp. 265-275
  • Manna, P.R., Stocco, D.M., Crosstalk of CREB and Fos/Jun on a single cis-element: transcriptional repression of the steroidogenic acute regulatory protein gene (2007) J. Mol. Endocrinol., 39, pp. 261-277
  • Mao, L., Yuan, L., Slakey, L.M., Jones, F.E., Burow, M.E., Hill, S.M., Inhibition of breast cancer cell invasion by melatonin is mediated through regulation of the p38 mitogen-activated protein kinase signaling pathway (2010) Breast Cancer Res., 12, pp. R107
  • Matzkin, M.E., Gonzalez-Calvar, S.I., Mayerhofer, A., Calandra, R.S., Frungieri, M.B., Testosterone induction of prostaglandin-endoperoxide synthase 2 expression and prostaglandin F2α production in hamster Leydig Cells (2009) Reproduction, 138, pp. 163-175
  • McLachlan, R.I., Rajpert-De Meyts, E., Hoei-Hansen, C.E., de Kretser, D.M., Skakkebaek, N.E., Histological evaluation of the human testis-approaches to optimizing the clinical value of the assessment (2007) Human Reprod., 22, pp. 2-16
  • Minneman, K.P., Wurtmann, R.J., Effects of pineal compounds on mammals (1975) Life Sci., 17, pp. 1189-1200
  • Moore, R.Y., The innervation of the mammalian pineal gland (1978) The Pineal and Reproduction, Progress in Reproductive Biology, pp. 1-29. , Karger, Basel, R.J. Reiter (Ed.)
  • Nduhirabandi, F., Du Toit, E.F., Blackhurst, D., Marais, D., Lochner, A., Chronic melatonin consumption prevents obesity-related metabolic abnormalities and protects the heart against myocardial ischemia and reperfusion injury in a prediabetic model of diet-induced obesity (2011) J. Pineal Res., 50, pp. 171-182
  • Ozbek, E., Ilbey, Y.O., Ozbek, M., Simsek, A., Cekmen, M., Somay, A., Melatonin attenuates unilateral ureteral obstruction-induced renal injury by reducing oxidative stress, iNOS, MAPK, and NF-kB expression (2009) J. Endourol., 23, pp. 1165-1173
  • Pfaffl, M.W., A new mathematical model for relative quantification in real-time RT-PCR (2001) Nucleic. Acid. Res., 29, pp. e45
  • Reiter, R.J., Pineal control of reproduction (1981) Prog. Clin. Biol. Res., 59 B, pp. 349-355
  • Reiter, R.J., Pineal melatonin cell biology of its synthesis and of its physiological interactions (1991) Endocr. Rev., 12, pp. 151-180
  • Reiter, R.J., The melatonin rhythm: both a clock and a calendar (1993) Experientia, 49, pp. 654-664
  • Reiter, R.J., The pineal and its hormones in the control of reproduction in mammals (1980) Endocr. Rev., 1, pp. 109-131
  • Rios, E.R., Venâncio, E.T., Rocha, N.F., Woods, D.J., Vasconcelos, S., Macedo, D., Sousa, F.C., Fonteles, M.M., Melatonin: pharmacological aspects and clinical trends (2010) Int. J. Neurosci., 120, pp. 583-590
  • Silber, S.J., Rodriguez-Rigau, L.J., Quantitative analysis of testicle biopsy: determination of partial obstruction and prediction of sperm count after surgery for obstruction (1981) Fertil. Steril., 36, pp. 480-485
  • Silber, S.J., Sertoli cell only syndrome (1996) Human Reprod., 11, p. 229
  • Silber, S.J., Nagy, Z., Devroey, P., Tournaye, H., Van Steirteghem, A.C., Distribution of spermatogenesis in the testicles of azoospermic men: the presence or absence of spermatids in the testes of men with germinal failure (1997) Human Reprod., 12, pp. 2422-2428
  • Sinha Hikim, A.P., Amador, A.G., Bartke, A., Russell, L.D., Structure/function relationships in active and inactive hamster Leydig cells: a correlative morphometric and endocrine study (1989) Endocrinology, 125, pp. 1844-1856
  • Sinha Hikim, A.P., Chandrashekar, V., Bartke, A., Russell, L.D., Sentinels of Leydig cell structural and functional changes in golden hamsters in early testicular regression and recrudescence (1993) Int. J. Androl., 16, pp. 324-342
  • Stankov, B., Reiter, R.J., Melatonin receptors: current status, facts and hypothesis (1990) Life Sci., 44, pp. 971-982
  • Stefulj, J., Hortner, M., Ghosh, M., Schauenstein, K., Rinner, I., Wolfler, A., Semmler, J., Liebmann, P.M., Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat (2001) J. Pineal Res., 30, pp. 243-247
  • Tijmes, M., Pedraza, R., Valladares, L., Melatonin in the rat testes: evidence of local synthesis (1996) Steroids, 61, pp. 65-68
  • Tsatsanis, C., Androulidaki, A., Dermitzaki, E., Gravanis, A., Margioris, A.N., Corticotropin releasing factor receptor 1 (CRF1) and CRF2 agonists exert an anti-inflammatory effect during the early phase of inflammation suppressing LPS-induced TNF-alpha release from macrophages via induction of COX-2 and PGE2 (2007) J. Cell Physiol., 210, pp. 774-783
  • Tsukamoto, N., Otsuka, F., Miyoshi, T., Inagaki, K., Nakamura, E., Terasaka, T., Takeda, M., Makino, H., Functional interaction of bone morphogenetic protein and growth hormone releasing peptide in adrenocorticotropin regulation by corticotrope cells (2011) Mol. Cell. Endocrinol., 344, pp. 41-50
  • Wang, W., Ji, P., Dow, K.E., Corticotropin-releasing hormone induces proliferation and TNF-alpha release in cultured rat microglia via MAP kinase signalling pathways (2003) J. Neurochem., 84, pp. 189-195
  • Wang, W., Zhang, X., Yang, L., Liu, D., Liu, G., J Zhou, Lipopolysaccharide upregulates the expression of corticotropin-releasing hormone via MAP kinase pathway in rat peritoneal macrophages (2012) Mol. Cell. Biochem., 361, pp. 1-7
  • Wurtman, R.J., Axelrod, J., The physiologic effects of melatonin and the control of its biosynthesis (1966) Probl. Actuels. Endocrinol. Nutr., 10, pp. 189-200
  • Yin, J., Liu, Y.H., Xu, Y.F., Zhang, Y.J., Chen, J.G., Shu, B.H., Wang, J.Z., Melatonin arrests peroxynitrite-induced tau hyperphosphorylation and the overactivation of protein kinases in rat brain (2006) J. Pineal Res., 41, pp. 124-129
  • Zhang, Y., Liu, W., Ma, C., Geng, J., Li, Y., Li, S., Yu, F., Cong, B., Endoplasmic reticulum stress contributes to CRH-induced hippocampal neuron apoptosis (2012) Exp. Cell Res., 318, pp. 732-740

Citas:

---------- APA ----------
Rossi, S.P., Matzkin, M.E., Terradas, C., Ponzio, R., Puigdomenech, E., Levalle, O., Calandra, R.S.,..., Frungieri, M.B. (2012) . New insights into melatonin/CRH signaling in hamster Leydig cells. General and Comparative Endocrinology, 178(1), 153-163.
http://dx.doi.org/10.1016/j.ygcen.2012.04.031
---------- CHICAGO ----------
Rossi, S.P., Matzkin, M.E., Terradas, C., Ponzio, R., Puigdomenech, E., Levalle, O., et al. "New insights into melatonin/CRH signaling in hamster Leydig cells" . General and Comparative Endocrinology 178, no. 1 (2012) : 153-163.
http://dx.doi.org/10.1016/j.ygcen.2012.04.031
---------- MLA ----------
Rossi, S.P., Matzkin, M.E., Terradas, C., Ponzio, R., Puigdomenech, E., Levalle, O., et al. "New insights into melatonin/CRH signaling in hamster Leydig cells" . General and Comparative Endocrinology, vol. 178, no. 1, 2012, pp. 153-163.
http://dx.doi.org/10.1016/j.ygcen.2012.04.031
---------- VANCOUVER ----------
Rossi, S.P., Matzkin, M.E., Terradas, C., Ponzio, R., Puigdomenech, E., Levalle, O., et al. New insights into melatonin/CRH signaling in hamster Leydig cells. Gen. Comp. Endocrinol. 2012;178(1):153-163.
http://dx.doi.org/10.1016/j.ygcen.2012.04.031