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Catecholamine-synthesizing enzymes in the adult and prenatal human testis

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Abstract

Catecholamines play functional roles in the mature and developing mammalian testis but the cell types responsible for their local synthesis are still controversially discussed. Here, we demonstrate that four enzymes involved in the biosynthesis of catecholamines, namely, tyrosine hydroxylase (TH), aromatic amino acid decarboxylase (AADC), dopamine β-hydroxylase (DBH) and phenylethanolamine- N-methyltransferase (PNMT), are expressed in Leydig cells of the human testis. Tyrosine hydroxylase, the key enzyme of the biosynthesis of catecholamines, was localized to Leydig cells both at the transcript level (by RT-PCR analyses and by in situ hybridization assays) and at the protein level (by immunoblotting and by immunohistochemistry). The other enzymes were also demonstrated in Leydig cells by RT-PCR and immunohistochemical analyses. The presence of TH, AADC, DBH, and PNMT in human Leydig cells was found, in addition, by immunohistochemical approaches carried out on sections from prenatal human testes. Thus, the present study identifies the Leydig cells as the presumed sites of catecholamine production in both the mature and fetal human testes and further supports the previously recognized neuroendocrine characteristics of this cell type.

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References

  • Baker H, Abate C, Szabo A, Joh TH (1991) Species-specific distribution of aromatic L-aminoacid decarboxylase in the rodent adrenal gland, cerebellum, and olfactory bulb. J Comp Neurol 305:119–129

    Article  PubMed  CAS  Google Scholar 

  • Baumgarten HG, Holstein AF (1976) Catecholaminhaltige Nervenfasern im Hoden des Menschen. Z Zellforsch 79:389–395

    Article  Google Scholar 

  • Bohn MC (1983) Role of glucocorticoids in expression and development of phenylethanolamine N-methyltransferase (PNMT) in cells derived from the neural crest: a review. Psychoneuroendocrinology 8:381–390

    Article  PubMed  CAS  Google Scholar 

  • Bohn MC, Goldstein M, Black IB (1982) Expression of phenylethanolamine N-methyltransferase in rat sympathetic ganglia and extra-adrenal chromaffin tissue. Dev Biol 89:299–308

    Article  PubMed  CAS  Google Scholar 

  • Bohn MC, Kessler JA, Adler JE, Markey K, Goldstein K, Black IB (1984) Simultaneous expression of the SP-peptidergic and noradrenergic phenotypes in rat sympathetic neurons. Brain Res 298:378–381

    Article  PubMed  CAS  Google Scholar 

  • Campos MB, Vitale ML, Ritta MN, Chiocchio SR, Calandra RS (1990a) Catecholamine distribution in adult rat testis. Andrologia 22:247–250

    Article  PubMed  CAS  Google Scholar 

  • Campos MB, Vitale ML, Calandra RS, Chiocchio SR (1990b) Serotonergic innervation of the rat testis. J Reprod Fert 88:475–479

    CAS  Google Scholar 

  • Davidoff M, Schulze W (1990) Combination of the peroxidase anti-peroxidase (PAP)- and avidin-biotin-peroxidase complex (ABC)-techniques: an amplification alternative in immunocytochemical staining. Histochemistry 93:531–536

    Article  PubMed  CAS  Google Scholar 

  • Davidoff MS, Schulze W, Middendorff R, Holstein AF (1993) The Leydig cell of the human testis—a new member of the diffuse neuroendocrine system. Cell Tissue Res 271:429–439

    Article  PubMed  CAS  Google Scholar 

  • Davidoff MS, Middendorff R, Holstein A-F (1996) Dual nature of Leydig cells of the human testis. Biomed Rev 6:11–41

    Google Scholar 

  • Davidoff MS, Middendorff R, Pusch W, Müller D, Wichers S, Holstein AF (1999) Sertoli and Leydig cells of the human testis express neurofilament triplet proteins. Histochem Cell Biol 111:173–187

    Article  PubMed  CAS  Google Scholar 

  • Davidoff MS, Middendorff R, Köfüncü E, Müller D, Ježek D, Holstein AF (2002) Leydig cells of the human testis possess astrocyte and oligodendrocyte marker molecules. Acta Histochem 104:39–49

    Article  PubMed  CAS  Google Scholar 

  • Davidoff MS, Middendorff R, Enikolopov E, Riethmacher D, Holstein AF, Müller D (2004) Progenitor cells of the testosterone-producing Leydig cells revealed. J Cell Biol 167:935–944

    Article  PubMed  CAS  Google Scholar 

  • Dumas S, Horelou P, Helin C, Mallet J (1992) Co-expression of tyrosine hydroxylase messenger RNA 1 and 2 in human ventral mesencephalon revealed by digoxigenin- and biotin-labelled oligodeoxyribonucleotides. J Chem Neuroanat 5:11–18

    Article  PubMed  CAS  Google Scholar 

  • Ehrlich ME, Evinger M, Regunathan S, Teitelman G (1994) Mammalian adrenal chromaffin cells coexpress the epinephrine-synthesizing enzyme and neuronal properties in vivo and in vitro. Dev Biol 163:480–490

    Article  PubMed  CAS  Google Scholar 

  • Ersenberger U, Esposito L, Partimo S, Huber K, Franke A, Bixby JL, Kalcheim C, Unsicker K (2005) Expression of neural markers suggests heterogeneity of chick sympathoadrenal cells prior to invasion of the adrenal anlagen. Cell Tissue Res 319:1–13

    Article  PubMed  CAS  Google Scholar 

  • Evain D, Morera AM, Saez JM (1976) Glucocorticoid receptors in interstitial cells of the rat testis. J Setroid Biochem 7:1135–1139

    Article  CAS  Google Scholar 

  • Frungieri MB, Gonzales-Calvar SI, Rubio M, Ozu M, Lustig L, Calandra RS (1999) Serotonin in golden hamster testes: testicular levels, immunolocalization and role during sexual development and photoperiodic regression-recruidance transition. Neuroendocrinology 69:299–308

    Article  PubMed  CAS  Google Scholar 

  • Frungieri MB, Urbanski HF, Höhne-Zell B, Mayerhofer A (2000) Neuronal elements in the testis of the Rhesus monkey: ontogeny, characterization and relationship to testicular cells. Neuroendocrinoly 71:43–50

    Article  CAS  Google Scholar 

  • Grima B, Lamouroux A, Boni C, Julien J-F, Javoy-Agid F, Mallet J (1987) A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics. Nature 326:707–711

    Article  PubMed  CAS  Google Scholar 

  • Holstein AF, Davidoff MS (1997) Organization of the intertubular tissue of the human testis. In: Delfino A (ed) Recent advances in microscopy of cells, tissues and organs, PM Motta, Rome, pp 569–577

    Google Scholar 

  • Ichinose K, Kurosawa Y, Titani K, Fujita K, Nagatsu T (1989) Isolation and characterization of a cDNA clone encoding human aromatic L-amino acid decarboxylase. Biochem Biophys Res Commun 164:1024–1030

    Article  PubMed  CAS  Google Scholar 

  • Ichinose H, Ohye T, Fujita K, Yoshida M, Ueda S, Nagatsu T (1993) Increased heterogeneity of tyrosine hydroxylase in humans. Biochem Biophys Res Commun 195:158–165

    Article  PubMed  CAS  Google Scholar 

  • Ikemoto K, Nagatsu I, Nishimura A, Nishi K, Arai R (1998) Do all of human midbrain tyrosine hydroxylase neurons synthesize dopamine? Brain Res 805:255–258

    Article  PubMed  CAS  Google Scholar 

  • Ikemoto K, Kitahama K, Nishimura A, Jouvet A, Nishi K, Arai R, Jouvet M, Nagatsu I (1999) Tyrosine hydroxylase and aromatic L-amino acid decarboxylase do not coexist in neurons in the human anterior cingulated cortex. Neurosci Lett 269:37–40

    Article  PubMed  CAS  Google Scholar 

  • Jaeger CB, Ruggiero DA, Albert VR, Joh DH, Reis DJ (1984) Immunocytochemical localization of aromatic L-amino acid decarboxylase. In: Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy, classical transmitters in the CNS, vol 2, Part 1. Elsevier, Amsterdam, pp 378–408

  • Kaneda N, Kobayashi K, Ichinose H, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T (1987) Isolation of a novel cDNA clone for human tyrosine hydroxylase: alternative RNA splicing produces four kinds of mRNA from a single gene. Biochem Biophys Res Commun 146:971–975

    Article  PubMed  CAS  Google Scholar 

  • Kaneda N, Ichinose H, Kobayashi K, Oka K, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T (1988) Molecular cloning of cDNA and chromosomal assignment of the gene for human phenylethanolamine N-methyltransferase, the enzyme for epinephrine biosynthesis. J Biol Chem 263:7672–7677

    PubMed  CAS  Google Scholar 

  • Kawamura M, Schwartz JP, Nomura T, Kopin IJ, Goldstein DS, Huynh T-T, Hooper DR, Harvey-White J, Eisenhofer G (1999) Differential effects of chemical sympathectomy on expression and activity of tyrosine hydroxylase and levels of catecholamines and DOPA in peripheral tissues of rats. Neurochem Res 24:25–32

    Article  PubMed  CAS  Google Scholar 

  • Kitamura K, Ikemoto K, Jouvet A, Nagatsu T, Geffard M, Okamura H, Pearson J (1998) Dopamine synthesizing enzymes in paraventricular hypothalamic neurons of the human and monkey (Macaca fuscata). Neurosci Lett 243:1–4

    Article  PubMed  Google Scholar 

  • Lamouroux A, Vigni A, Faucon Biguet N, Darmon MC, Franck R, Henry JP, Mallet J (1987) The primary structure of human dopamine-beta-hydroxylase: insights into the relationship between the soluble and the membrane-bound forms of the enzyme. EMBO J 6:3931–3937

    PubMed  CAS  Google Scholar 

  • Mayerhofer A (1996a) Leydig cell regulation by catecholamines and neuroendocrine messengers. In: Payne AH, Hardy MP, Russell LD (eds) The Leydig cell. Cache River Press, Vienna, IL, pp 407–417

    Google Scholar 

  • Mayerhofer A, Bartke A, Steger RW (1989) Catecholamine effects on testicular testosterone production in the gonadally active and gonadally regressed adult golden hamster. Biol Reprod 40:752–761

    Article  PubMed  CAS  Google Scholar 

  • Mayerhofer A, Calandra RS, Bartke A (1991) Cyclic adenosine monophosphate (cAMP) does not mediate the stimulatory action of norepinephrine on testosterone production by the testis of the golden hamster. Life Sci 48:1109–1114

    Article  PubMed  CAS  Google Scholar 

  • Mayerhofer A, Steger RW, Gow G, Bartke A (1992) Catecholamines stimulate testicular testosterone release in the immature golden hamster via interaction with testicular alpha- and beta-adrenergic receptors. Acta Endocrinol (Copenh) 127:526–530

    CAS  Google Scholar 

  • Mayerhofer A, Bartke A, Began T (1993) Catecholamines stimulate testicular steroidogenesis in vitro in the Sibirian hamster, Phodopus sungorus. Biol Reprod 48:883–888

    Article  PubMed  CAS  Google Scholar 

  • Mayerhofer A, Danilchik M, Francis Pau K-Y, Lara HE, Russell LD, Ojeda SR (1996b) Testis of prepubertal Rhesus monkeys receives a dual catecholaminergic input provided by the extrinsic innervation and intragonadal source of catecholamines. Biol Reprod 55:509–518

    Article  PubMed  CAS  Google Scholar 

  • Mayerhofer A, Frungieri MB, Fritz S, Bulling A, Jessberger B, Vogt H-J (1999) Evidence for catecholaminergic, neuronlike cells in the adult human testis: changes associated with testicular pathologies. J Androl 20:341–347

    PubMed  CAS  Google Scholar 

  • Meister B, Hökfelt T, Steinbusch HW, Skagerberg G, Lindwall O, Geffard M, Joh TH, Cuello AC, Goldstein M (1988) Do tyrosine hydroxylase-immunoreactive neurons in the ventrolateral arcuate nucleus produce dopamine or only L-dopa? J Chem Neuroanat 1:59–64

    PubMed  CAS  Google Scholar 

  • Middendorff R, Davidoff M, Holstein AF (1993) Neuroendocrine marker substances in human Leydig cells—changes by disturbances of testicular functions. Andrologia 25:257–262

    Article  PubMed  CAS  Google Scholar 

  • Middendorff R, Müller D, Paust HJ, Davidoff MS, Mukhopadhyay AK (1996) Natriuretic peptides in the human testis: evidence for a potential role of C-type natriuretic peptide (CNP) in Leydig cells. J Clin Endocrinol Metab 81:4324–4328

    Article  PubMed  CAS  Google Scholar 

  • Middendorff R, Müller D, Wichers S, Holstein AF, Davidoff MS (1997) Evidence for production and functional activity of nitric oxide in seminiferous tubules and blood vessels of the human testis. J Clin Endocrinol Metab 82:4154–4161

    Article  PubMed  CAS  Google Scholar 

  • Middendorff R, Müller D, Mewe M, Mukhopadhyay AK, Holstein AF, Davidoff MS (2002) The tunica albuginea of the human testis is characterized by complex contraction and relaxation activities regulated by cyclic GMP. J Clin Endocrinol Metab 87:3486–3499

    Article  PubMed  CAS  Google Scholar 

  • Müller D, Mukhopadhyay AK, Speth RC, Guidone G, Potthast R, Potter LR, Middendorff R (2004) Spatiotemporal regulation of the two atrial natriuretic peptide receptors in testis. Endocrinology 145:1392–1401

    Article  PubMed  CAS  Google Scholar 

  • Novak CM, Nunez AA (1998) Tyrosine hydroxylase-and/or aromatic L-amino acid decarboxylase-containing cells in the suprachiasmatic nucleus of the Syrian hamster (Mesocricetus auratus). J Chem Neuroanat 14:87–94

    Article  PubMed  CAS  Google Scholar 

  • Pointis G, Latreille MT (1987) Catecholamine-induced stimulation of testosterone production by Leydig cells from fetal mouse testis. J Reprod Fert 80:321–326

    Article  CAS  Google Scholar 

  • Prince FP (1992) Ultrastructural evidence of indirect and direct autonomic innervation of human Leydig cells: comparison of neonatal, childhood and pubertal ages. Cell Tissue Res 269:383–390

    Article  PubMed  CAS  Google Scholar 

  • Prince FP (1996) Ultrastructural evidence of adrenergic, as well as cholinergic, nerve varicosities in relation to the lamina propria of the human seminiferous tubules during childhood. Tissue Cell 28:507–513

    Article  PubMed  CAS  Google Scholar 

  • Renshaw D, Thomson LM, Michael GJ, Carroll M, Kapas S, Hinson JP (2000) Adrenomedullin receptor is found exclusively in noradrenaline-secreting cells of the rat adrenal medulla. J Neurochem 74:1766–1772

    Article  PubMed  CAS  Google Scholar 

  • van Roijen JH, Ooms MP, Spaargaren MC, Baarends WM, Weber RFA, Grootegoed JA, Vreeburg JTM (1998) Immunoexpression of testis-specific histone 2B in human spermatozoa and testis tissue. Hum Reprod 13:1559–1566

    Article  PubMed  Google Scholar 

  • Romeo R, Pellitteri R, Russo A, Marcello MF (2004) Catecholaminergic phenotype of human Leydig cells. Ital J Anat Embryiol 109:45–54

    Google Scholar 

  • Ross CA, Ruggiero DA, Meeley MP, Park DH, Joh TH, Reis DJ (1984) A new group of neurons in hypothalamus containing phenylethanolamine N-methyltransferase (PNMT) but not tyrosine hydroxylase. Brain Res 306:349–353

    Article  PubMed  CAS  Google Scholar 

  • Saez JM, Morera AM, Haour F, Evain D (1977) Effects of in vivo administration of dexamethasone, corticotrophin and human chorionic gonadotropin on steroidogenesis and protein and DNA synthesis of testicular interstitial cells in prepuberal rats. Endocrinology 101:1256–1263

    Article  PubMed  CAS  Google Scholar 

  • Schulze W, Davidoff MS, Holstein AF (1987) Are Leydig cells of neural origin? Substance P-like immunoreactivity in human testicular tissue. Acta Endocrinol 115:373–377

    PubMed  CAS  Google Scholar 

  • Seil FJ, Johnson ML, Nishi R, Nilaver G (1992) Tyrosine hydroxylase expression in non-catecholaminergic cells in cerebellar cultures. Brain Res 569:164–168

    Article  PubMed  CAS  Google Scholar 

  • Setchell BP, Maddocks S, Brooks DE (1994) Anatomy, vasculature, innervation and fluids of the male reproductive tract. In: Knobil E, Neill JD (eds) The physiology of reproduction, 2nd edn. Raven Press, New York, pp 1063–1175

    Google Scholar 

  • Tinajero JC, Fabbri A, Duffau ML (1992) Regulation of corticotrophin-releasing factor secretion from Leydig cells by serotonin. Endocrinology 130:1780–1788

    Article  PubMed  CAS  Google Scholar 

  • Tinajero JC, Fabbri A, Clocca DR, Dufau ML (1993) Serotonin secretion from rat Leydig cells. Endocrinology 133:3026–3029

    Article  PubMed  CAS  Google Scholar 

  • Ungefroren H, Voss M, Jansen M, Roeder C, Henne-Bruns D, Kremer B, Kalthofff H (1998) Human pancreatic adenocarcinomas express Fas and Fas ligand yet are resistant to Fas-mediated apoptosis. Cancer Res 58:1741–1749

    PubMed  CAS  Google Scholar 

  • Unni E, Mayerhofer A, Zhang Y, Bhatnagar YM, Russel LD, Meistrich ML (1995) Increased accessibility of the N-terminus of testis-specific histone TH2B to antibodies in elongating spermatids. Mol Reprod Dev 42:210–219

    Article  PubMed  CAS  Google Scholar 

  • Unsicker K, Seidl K, Hofmann HD (1989) The neuro-endocrine ambiguity of sympathoadrenal cells. Int J Dev Neuroscience 7:413–417

    Article  CAS  Google Scholar 

  • Záborszky L, Léránth C (1985) Simultaneous ultrastructural demonstration of retrogradely transported horseradish peroxidase and choline acetyltransferase immunoreactivity. Histochemistry 82:529–53

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors are grateful to Mrs. M. Köhler and Mrs. Ch. Knies for their excellent technical assistance. This study was supported by the Deutsche Forschungsgemeinschaft (DA 459/1-1; MI 637/1-1), Bundesministerium für Bildung und Forschung (01 KY 9103/0 to D. Müller) and the “Verein zur Förderung der Forschung auf dem Gebiete der Fortpflanzung e.V.”

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Correspondence to Michail S. Davidoff.

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Davidoff, M.S., Ungefroren, H., Middendorff, R. et al. Catecholamine-synthesizing enzymes in the adult and prenatal human testis. Histochem Cell Biol 124, 313–323 (2005). https://doi.org/10.1007/s00418-005-0024-x

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