Abstract
The ability of the mammalian testis to produce estrogens is well known and Leydig cells represent an important source. Taking into account the widespread distribution of estrogen receptors in male gonad and additionnai expression of aromatase in germ cells, the role of estrogens in male reproduction is more complex than previously realized.
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References
Saez JM. Leydig cells: endocrine, paracrine and autocrine regulation. Endocr Rev 1994;15:574–626.
O’Donnell L, Robertson KM, Jones ME, Simpson ER. Estrogen and spermatogenesis. Endocr Rev 2001;22: 289–318.
Zondek B. Mass excretion of oestrogenic hormone in the urine of the stallion. Nature (London) 1934;193:209–210.
Goldzieher JW, Roberts IS. Identification of estrogen in the human testis. J Clin Endocrinol Metab 1952;12:143–150.
Baggett B, Eugel LL, Balderas L, Lanman G, Savard K, Dorfman RI. Conversion of C14-androgens to C14-estrogenic steroids by endocrine tissues. Endocrinology 1959;64:600–608.
Attal J. Levels of testosterone, androstenedione, estrone and estradiol-17β in the testes of fetal sheep. Endocrinology 1969;85:280–289.
Raeside JI. The isolation of estrone sulphate and estradiol-17β sulphate from stallion testis. Can J Biochem 1969;47:811–815.
Jayle MF, Scholler R, Sfikalis A, Héron M. Excrètion des phénolstéroïdes et des 17 cétostéroïdes après administration de gonadotropines chorioniques à des hommes. Clin Chem Acta 1962;7:212–220.
Kelch RP, Jenne MA, Weinstein R, Kaplan SL, Grumbach MM. Estradiol and testosterone secretion by human, simian and canine testes in males with hypogonadism and in male pseudohermaphrodites with the feminizing testes syndrome. J Clin Invest 1972;51:824–830.
Hess RA, Carnes K. The role of estrogen in the testis and the male reproductive tract: a review. Anim Reprod 2004;1:5–30.
Hendry WF, Parslow JM, Stedronska J. Exploratory scrotomy in 168 azoospermic males. Brit J Urol 1983; 55:785–791.
Carreau S, Genissel C, Bilinska B, Levallet J. The oestrogen sources in the testis and the reproductive tract of the male. Inter JAndrol 1999;22:211–223.
de Jong FH, Hey AH, van der Molen HJ. Oestradiol-17β and testosterone in rat testis tissue: effect of gonadotrophins, localization and production in vitro. J Endocrinol 1974;60: 409–449.
Valladares LE, Payne AH. Acute stimulation of aromatization in Leydig cells by human chorionic gonadotropin. Proc Natl acad Sci USA 1979;76:4460–4463.
Rommerts FFG, de Jong FH, Brinkmann AO, van der Molen HJ. Development and cellular localization of rat testicular aromatase activity. J Reprod Fert 1982;65:281–288.
Tsai-Morris CH, Aquilano DR, Dufau ML. Cellular localization of rat testicular aromatase activity during development. Endocrinology 1985;116:38–46.
Papadopoulos V, Carreau S, Szerman-Joly E, Drosdowsky MA, Dehennin L, Scholler R. Rat testis 17β-estradiol: identification by gas chromatography-mass spectrometry and age related cellular distribution. J Steroid Biochem 1986;24:1211–1216.
van der Molen HJ, Brinkmann AO, de Jong FH, Rommerts FFG. Testicular oestrogens. J Endocrinol 1981; 89:33–46.
Carreau S, Papadopoulos V, Drosdowsky MA. Stimulation of adult rat Leydig cell aromatase activity by a Sertoli cell factor. Endocrinology 1988;122:1103–1109.
Kurosumi M, Ishimura K, Fujita H, Osawa Y. Immunocytochemical localization of aromatase in rat testis. Histochemistry 1985;83:401–404.
Carpino A, Pezzi V, rago V, Bilinska B, Ando S. Immunolocalization of cytochrome P450 aromatase in rat testis during postnatal development. Tissue Cell 2001;33: 349–353.
Carreau S. (1994) Germ cells-Sertoli cells interactions and Leydig cell function. In: Dufau ML, Fabbri A, Isidori A, eds; Cell and Molecular Biology of the Testis: Frontiers in Endocrinology 5, Serono Symposia Publications, 1994: 137–148.
Papadopoulos V, Kamtchouing P, Drosdowsky MA, Hochereau de Reviers MT, Carreau S. Adult rat Sertoli cells secrete a factor or factors which modulate Leydig cell function. J Endocrinol 1987;114:459–467.
Levallet J, Carreau S. Aromatase gene expression in rat testicular cells. C R Acad Sc. Paris, 1997;320:123–129.
Genissel C, Carreau S. Regulation of the aromatase gene expression in mature rat Leydig cells. Mol Cell Endocrinol 2001;178:141–148.
Boitani C, Ritzen EM, Parvinen M. Inhibition of rat Sertoli cell aromatase by factor(s) secreted specifically at spermatogenic stages VII and VIII. Mol Cell Endocrinol 1981;23:1l–22.
Nitta H, Bunick D, Hess RA, et al. Germ cells of the mouse testis express P450 aromatase. Endocrinology 1993; 132: 1396–1401.
Bilinska B, Schmalz-Fraczek B, Kotula M, Carreau S. Photoperiod-dependent capability of androgen aromatization and the role of estrogens in bank vole testis visualized by means of immunohistichemistry. Mol Cell Endocrinol 2001;178:189–198.
Fraczek B, Bourguiba S, Carreau S, Bilinska B. Immunolocalization and activity of aromatase in the bank vole testes. Folia Histochem Cytobiol 2001;39:31–319.
Raeside JI, Renaud RL. Estrogen and androgen production by purified Leydig cells of mature boars. Biol Reprod 1983;28:727–733.
Saez JM, Sanchez P, Bertheion MC, Avallet O. Regulation of pig Leydig cell aromatase activity by gonadotropins and Sertoli cells. Biol Reprod 1989;41:813–820.
Conley AJ, Corbin CJ, Hinshelwood MM, et al. Functional aromatase expression in porcine adrenal gland and testis. Biol Reprod 1996;54:497–505.
Mutembei HM, pesch S, Schuler G, Hoffmann B. Expression of oestrogen receptors a and β and of aromatase in the testis of immature and mature boars. Reprod Dom Anim 2005; 40:228–236.
Weng Q, Medan MS, Watanabe G, Tsubota T, Tanioka Y, Taya K. Immunolocalization of steroidogenic enzymes P450scc, 3 β-HSD, P450cl7, and P450arom in Gottingen miniature pigs. J Reprod Dev 2005;51:299–304.
Almadhidi J, S’eralini GE, Fresnel J, Silberzahn P, Gaillard JL. Immunohistochemical localization of cytochrome P450 aromatase in equine gonads. J Histochem Cytochem 1995; 43:571–577.
Eisenhauer KM, McCue PM, Nayden DK, Osawa Y, Roser JF. Localization of aromatase in equine Leydig cells. Dornest Anim Endocrinol 1994;1l:291–298.
Sipahutar H, Sourdaine P, Moslemi S, Plainfossé B, Seralini GE. Immunolocalization of aromatase in stallion Leydig cells and seminiferous tubules. J Histochem Cytochem 2003;51: 311–318.
Payne AH, Kelch RP, Musich SS, Halpern ME. Intratesticular site of aromatization in the human. J Clin Endocrinol Metab 1976;42:1081–1087.
Papadopoulos V, Drosdowsky MA, Carreau S. On the existence of two Leydig cell populations in aged human testis. Ann NY Acad Sci 1987;513:356–359.
Inkster S, Yue W, Brodie A. Human testicular aromatase: immunocytochemical and biochemical studies. J Clin Endocrinol Metab 1995; 80:1941–1947.
Brodie A, Inkster S, Yue W. Aromatase expression in human male. Mol Cell Endocrinol 2001;178:23–28.
Lejeune H, Sanchez P, Saez JM. Enhancement of long-term testosterone secretion and steroidogenic enzyme expression in human Leydig cells by coculture with human Sertoli cellenriched preparations. Inter J Androl 1998;21:129–140.
Simpson ER, Mahendroo MS, Means GD, et al. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 1994;15:342–355.
Conley A, Hinshelwood M. Mammalian aromatases. Reproduction 2001;121:685–695.
Hickey GJ, Krasnow JS, Beattie WG, Richards JS. Aromatase cytochrome P450 in rat ovarian granulosa cells before and after luteinization: adenosine 3′, 5′-monophosphate-dependent and independent regulation. Cloning and sequencing of rat aromatase cDNA and 5′ genomic DNA. Mol Endocrinol 1990;4:3–12.
Simpson ER, Michael MD, Agarwal VR, Hinshelwood MM, Bulun SE, Zhao Y Expression of the CYP 19 (aromatase) gene: an unusual case of alternative promoter usage. FASEB J 1997;11:29–36.
Young M, McPhaul MJ. A steroidogenic factor-1 binding site and cyclic adenosine 3′,5′-monophosphate response elementlike elements are required for the activity of the rat aromatase promoter in rat Leydig tumor cell lines. Endocrinology 1998; 139:5082–5093.
Bourguiba S, Genissel C, Lambard S, Bouraima H, Carreau S. Regulation of aromatase gene expression in Leydig cells and germ cells. J Steroid Biochem Mol Biol 2003;86:335–343.
Lanzino M, Catalano S, Genissel C, et al. Aromatase messenger RNA is derived from the proximal promoter of the aromatase gene in Leydig, Sertoli and germ eclls of the rat testis. Biol Reprod 2001;64:1439–1443.
Fitzpatrick SL, Richards JS. Identification of a cyclic adenosine 3′,5′-monophosphate-response element in the rat aromatase promoter that is required for transcriptional activation in rat granulosa cells and R2C Leydig cells. Mol Endocrinol 1994;8:1309–1319.
Young M, Lephart ED, McPhaul MJ. Expression of aromatase cytochrome P450 in rat Leydig tumor cells. J Steroid Biochem Mol Biol 1997;63:37–44.
Genissel C, Levallet J, Carreau S. Regulation of cytochrome P450 aromatase gene expression in the adult rat Leydig cells. Comparison with estradiol production. J Endocrinol 2001;168:95–105.
Pezzi V, Sirianni R, Chimento A, et al. Differential expression of steroidogenic factor-1/adrenal 4 binding protein and liver receptor homolog-1 (LRH-l)/fetoprotein transcription factor in the rat testis: LRH-1 as a potential regulator of testicular aromatase expression. Endocrinology 2004;145:2186–2196.
Papadopoulos V, Drosdowsky MA, Carreau S. In vitro effects off prolactin and dexamethasone on rat Leydig cell aromatase activity. Andrologia 1986;18:79–83.
Rigaudière N, Grizard G, Boucher D. Aromatase activity in purified Leydig cells from adult rat. Comparative effects of insulin, IGF-I and hCG. Acta Endocrinol(Copenh) 1989; 121:677–685.
Gancarczyk M, Tworzydlo W, Szlachta A, Sadowska J, Bilinska B. Hormonal regulation of oestrogen formation by Leydig cells in vitro: an immunocytochemical approach. Folia Biol 2003;51:181–188.
Benahmed M, Bernier M, Ducharme IR, Saez JM. Steroidogenesis of cultured purified pig Leydig cells: secretion and effects of estrogens. Mol Cell Endocrinol 1982;28:705–716.
Wang ZJ, Jeffs B, ito M, et al. Aromatase (Cyp19) expression is up-reguated by targeted disruption of Dax1. Proc Natl Acad Sci USA 2001;98:7988–7993.
Bulun SE, Rosenthal IM, Brodie AM, et al. Use of tissue-specific promoters in the regulation of aromatase cytochrome P450 gene expression in human testicular and ovarian sex cord tumors as well as in mormal fetal and adut gonads. J Clin Endocrinol Metab 1993;77:1616–1621.
Gurates B, Amsterdam A, Tamura M, et al. WT1 and DAX-1 regulate SF-1-mediated human P450arom gene expression in gonadal cells. Mol Cell Endocrinol 2003;208:61–75.
Carreau S, Bourguiba S, Lambard S, Silandre D, Delalande C. The promter(s) of the aromatase gene in male testicular cells. Reprod Biol 2004;4:23–34.
Roger C, Lambard S, Bouskine A, et al. Estrogen-induced growth inhibition of human seminoma cells expresing estrogen receptor β and aromatase. J Mol Endocrinol 2005;35: 191–199.
Tsubota T, Nitta H, Osawa Y, et al. Immunolocalization of steroidogenic enzymes, P450scc, 3β HSD, P450cl7, and P450arom in the hokkaido brown bear (Ursus arctos yesoensis) testis. Gen Comp Endocrinol 1993;92:439–434.
Tsubota T, Howell-Skalla L, Nitta H, et al. Seasonal changes in spermatogenesis and testicular steroidogenesis in the male black bear Ursus americanus. J Reprod Fert 1997; 109:21–27.
Levallet J, Bilinska B, Mittre H, Genissel C, Fresnel J, Carreau S. Expression and immunolocalization of functional cytochrome P450 aromatase in mature rat testicular cells. Biol Reprod 1998;58:919–926.
Bourguiba S, Chater S, Delalande C, Benhamed M, Carreau S. Regulation of aromatase gene expression in purified germ eclls of adult male rats: effects of TGFβ, TNFα and cyclic AMP. Biol Reprod 2003;69:592–601.
Janulis L, Bahr JM, Hess RA, Bunick D. P450 aromatase messenger ribonucleic acid expression in male rat germ cells: detection by reverse transcription-polymerase chain reaction amplification. J Androl 1996;17:651–658.
Carreau S, Bourguiba S, Lambard S, Galeraud-Denis I, Genissel C, Levallet J. Reproductive system: aromatase and estrogens. Mol Cell Endocrinol 2002;193:137–143.
Lambard S, Silandre D, Delalande C, Denis-Galerad I, Bourguiba S, Carreau S. Aromatase in testis: expression and roile in male reproduction. J Steroid Biochem Mol Biol 2005;95:63–69.
Hess MF, Roser JF. Immunocytochemical localization of cytochrome P450 aromatase in the testis of prepubertal, pubertal and postpubertal horses. Theriogenology 2004;61: 293–299.
Carreau S. Paracrine control of human Leydig cell and Sertoli cell functions. Folia Histochem Cytobiol 1996;3:111–119.
Lambard S, Galeraud-Denis I, Bouraïma H, Bourguiba S, Chocat A, Carreau S. Expression of aromatase in human ejaculated spermatozoa: a putative marker of motility. Mol Human Reprod 2003;9:117–124.
Lambard S, Carreau S. Aromatase and estrogens in human male germ cells. Int J Androl 2005, in press.
Nakhala AM, Mather JP, Jänne OA, Bardin CW. Estrogen and androgen receptors in Sertoli, Leydig, myoid and epithelial cells: effects of time in culture and cell density. Endocrinology 1984;115:121–128.
Carreau S, Lambard S, Delalande C, Denis-Galeraud I, Bilinska B, Bourguiba S. Aromatase expression and role of estrogens in male gonad: a review. Reprod Biol Endocrinol 2003;1:35–43.
Kuiper GGJM, Carlsson B, Grandien K, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors a and β. Endocrinology 1997; 138:863–870.
Saunders PTK, Fisher JS, Sharpe RM, Millar MR. Expression of oestrogen receptor beta (ER-β) occurs in multiple cell types, including some germ cells, in the rat testis. J Endocrinol 1998;156:R13–R17.
Saunders PTK, Sharpe RM, Williams K, et al. Differential expression of oestrogen receptor-α and-β proteins in the testes and male reproductive system of human and non-human primates. Mol Hum Reprod 2001;7:227–236.
Majdic G, Sharpe RM, Saunders PTK. Maternal oestrogen/ xenoestrogen exposure alters expression of steroidogenic factor-1 (SF-l/Ad4BP) in the fetal rat testis. Mol Cell Endocrinol 1997;127:91–98.
Abney TO. The potential roles of estrogens in regulating Leydig cell development and function: a review. Steroids 1999;64:610–617.
Delbes G, Levacher C, Duquenne C, Racine C, Pakarinen P, Habert R. Endogenous estrogens inhibit mouse fetal Leydig cell development via estrogen receptor-a. Endocrinology 2005;146:2454–2461.
Ciocca DR, Winters CA, Dufau ML. Expression of an estrogen-related protein in rat testis Leydig cells. J Steroid Biochem 1986;24:219–229.
Orczyk GP, Mordes JP, Longcope C. Aromatase activity in a rat Leydig cell tumor. Endocrinology 1987; 120:1482–1489.
Kerlan V, Nahoul K, Abalain JH, Mangin P, Bercovici JP. Oestrogen secreting Leydig cell tumor and GnRH agonsit invivo and in-vitro studies. Clin Endocrinol 1992;37:221–226.
Kotula-Balak M, Slomczynska M, Fraczek B, et al. Complementary approaches demonstrate that cellular aromatization in the bank vole testris is related to photoperiod. Eur J Histochem 2003;47:55–62.
Raeside JI, Renaud RL, Friendship RM. Differences in aromatase activity between Leydig cells from the srotal and abdominal testis in the naturally unilateral-cryptorchid boar. Biol Reprod 1988;39:566–572.
Fowler KA, Gill K, Kirma N, Dillehay DL, Tekmal RR. Overexpression oaromatase leads to development of testicular Leydig cell tumors. Am J Pathol 2000;156:347–353.
Li XD, Nokkala E, Yan W, et al. Altered structure and function of reproductive organs in transgenic male mice overexpressing human aromatase. Endocrinology 2001;142:2435–2442.
Song WC, Qian Y, Sun X, Negishi M. Cellular localization and regulation of expression of testicular estrogen sulfotransferase. Endocrinology 1997; 138:5006–5012.
Couse JF, Korach KS. Estrogen receptor null mice: what have we learned and where will they lead us? Endocr Rev 1999; 20:358–417.
Rochira V, Granata ARM, Madeo B, Zirilli L, Rossi G, Carani C. Estrogens in males: what we have learned in last 10 years? Asian J Androl 2005;7:3–20.
Luconi M, Francavilla F, Porazzi I, Macerola B, Forti G, Baldi I. Human spermatozoa as a model for studying membrane receptors mediating rapid nongenomic effects of progesterone and estrogens. Steroids 2004;69:553–559.
Carreau S, Delalande C, Silandre D, Bourguiba S, Lambard S. Aromatase and estrogen receptors in male reproduction. Mol Cell Endocrinol 2006, in press.
Kotula-Balak M, Gancarczyk M, Sadowska J, Bilinska B. The expression of aromatase, estrogen receptor-α and estrogen receptor-β in mouse Leydig cells in vitro that derived from cryptorchid males. Eur J Histochem 2005;49:59–62.
Pomerantz DK. Effects of in vivo gonadotropin treatment on estrogen levels in the testis of the immature rat. Biol Reprod 1979;21:1247–1255.
Pudney J, Canick JA, Clifford NM, Knopp JB, Callard GV. Location of enzymes of androgen and estrogen biosynthesis in the testis of the ground squirrel. Biol Reprod 1985;33:971–980.
Raeside JI. Stimulation of aromatase activity in immature porcine Leydig cells by fibroblast growth factor (FGF). Biochem Biophys Res Comm 1988;151:163–169.
Raeside JI. Renaud RL, Friendship RM. Aromatization of 19-norandrogens by procine Leydig cells. J Steroid Biochem 1989;32:729–735.
Fraczek B, Kotula-Balak M, wojtusiak A, Pierscinski A, Bilinska B. Cytochrome P450 aromatase in the testis of immature and mature pigs. Reprod Biol 2001;1:51–59.
Bilinska B, Lesniak M, Schmalz B. Are ovine Leydig cells able to aromatize androgens? Reprod Fert Dev 1997;9:1–7.
Martel C, Meiner MH, Gagné D, Simard J, Labrie F. Widespread tissue distribution of steroid sulfatase, 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD), 17β-HSD, 5α-reductase and aromatase activities in the rhesus monkey. Mol Cell Endocrinol 1994; 104:103–101.
Kuiper GGJM, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 1996; 93:5925–5930.
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Carreau, S. (2007). Leydig Cell Aromatase. In: Payne, A.H., Hardy, M.P. (eds) The Leydig Cell in Health and Disease. Contemporary Endocrinology. Humana Press. https://doi.org/10.1007/978-1-59745-453-7_13
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