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Gene expression profiles of estrogen receptors α and β in the fetal bovine hypothalamus and immunohistochemical characterization during development

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Abstract

Steroid hormones intervene in the structural and functional regulation of neuronal processes during development and thus determine brain differentiation. The effects of estrogens are mediated by two transcription factors, namely estrogen receptor α (ER-α) and estrogen receptor β (ER-β), that regulate the expression of target genes through their binding to specific DNA target sequences. We describe the mRNA expression of ER-α and ER-β in the hypothalamus of developing male and female bovines as revealed by quantitative real-time polymerase chain reaction, and the distribution of the two ERs in hypothalamic sections of all fetal stages as shown by immunohistochemistry. The expression profiles of the mRNAs of both ERs are mutually correlated throughout the gestation period, and their levels increase significantly in the last stages of gestation. No sexual differences in the mRNA expression of either ER-α or ER-β have been found in our fetal specimens. The use of specific antisera against ER-α and ER-β has allowed us to characterize and confirm the distribution of these receptors in the hypothalami of all fetal stages considered. Our results offer detailed information concerning the distribution of ER-α and ER-β in the developing bovine hypothalamus and provide additional insights into the processes involved in the hypothalamic development of a mammal with a long gestation and a highly gyrencephalic brain.

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References

  • Ábrahám IM, Todman MG, Korach KS, Herbison AE (2004) Critical in vivo roles for classical estrogen receptors in rapid estrogen actions on intracellular signaling in mouse brain. Endocrinology 145:3055–3061

    Article  PubMed  Google Scholar 

  • Al-Bader MD, El-Abdallah AA, Redzic ZB (2008) Ontogenic profile of estrogen receptor alpha and beta mRNA and protein expression in fetal rat brain. Neurosci Lett 8:222–226

    Article  Google Scholar 

  • Arai Y, Sekine Y, Murakami S (1996) Estrogen and apoptosis in the developing sexually dimorphic preoptic area in female rats. Neurosci Res 25:403–407

    Article  CAS  PubMed  Google Scholar 

  • Arnold AP, Gorski RA (1984) Gonadal steroid induction of structural sex differences in the central nervous system. Annu Rev Neurosci 7:413–442

    Article  CAS  PubMed  Google Scholar 

  • Asimiadou S, Bittigau P, Felderhoff-Mueser U, Manthey D, Sifringer M, Pesditschek S, Dzietko M, Kaindl AM, Pytel M, Studniarczyk D, Mozrzymas JW, Ikonomidou C (2005) Protection with estradiol in developmental models of apoptotic neurodegeneration. Ann Neurol 58:266–276

    Article  CAS  PubMed  Google Scholar 

  • Bakker O (2006) Comparison of qPCR assays using the LightCycler® 2.0 instrument and either SYBR green I intercalation or the Universal Probe Library as detection format. Biochemica 3:8–10

    Google Scholar 

  • Bakker J, Brock O (2010) Early oestrogens in shaping reproductive networks: evidence for a potential organisational role of oestradiol in female brain development. J Neuroendocrinol 22:728–735

    CAS  PubMed  Google Scholar 

  • Bleier R, Byne W, Siggelkow I (1982) Cytoarchitectonic sexual dimorphisms of the medial preoptic and anterior hypothalamic areas in guinea pig, rat, hamster, and mouse. J Comp Neurol 212:118–130

    Article  CAS  PubMed  Google Scholar 

  • Brock O, Baum MJ, Bakker J (2011) The development of female sexual behavior requires prepubertal estradiol. J Neurosci 31:5574–5578

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cozzi B, Giacomello M, Zambenedetti P, Bolognin S, Rossipal E, Peruffo A, Zatta P (2010) Ontogenesis and migration of metallothionein I/II-containing glial cells in the human telencephalon during the second trimester. Brain Res 23:16–23

    Article  Google Scholar 

  • Fan X, Warner M, Gustafsson JA (2006) Estrogen receptor beta expression in the embryonic brain regulates development of calretinin-immunoreactive GABAergic interneurons. Proc Natl Acad Sci U S A 103:19338–19343

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fan X, Xu H, Warner M, Gustafsson JA (2010) ERbeta in CNS: new roles in development and function. Prog Brain Res 181:233–250

    Article  CAS  PubMed  Google Scholar 

  • Fried G, Andersson E, Csöregh L, Enmark E, Gustafsson JA, Aanesen A, Osterlund C (2004) Estrogen receptor beta is expressed in human embryonic brain cells and is regulated by 17beta-estradiol. Eur J Neurosci 20:2345–2354

    Article  CAS  PubMed  Google Scholar 

  • Friedman WJ, McEwen BS, Toran-Allerand CD, Gerlach JL (1983) Perinatal development of hypothalamic and cortical estrogen receptors in mouse brain: methodological aspects. Brain Res 313:19–27

    Article  CAS  PubMed  Google Scholar 

  • Gabai G, Marinelli L, Simontacchi C, Bono GG (2004) The increase in plasma C19Delta5 steroids in subcutaneous abdominal and jugular veins of dairy cattle during pregnancy is unrelated to estrogenic activity. Steroids 69:121–127

    Article  CAS  PubMed  Google Scholar 

  • González M, Cabrera-Socorro A, Pérez-García CG, Fraser JD, López FJ, Alonso R, Meyer G (2007) Distribution patterns of estrogen receptor alpha and beta in the human cortex and hippocampus during development and adulthood. J Comp Neurol 503:790–802

    Article  PubMed  Google Scholar 

  • Gorosito SV, Lorenzo AG, Cambiasso MJ (2008) Estrogen receptor alpha is expressed on the cell-surface of embryonic hypothalamic neurons. Neuroscience 154:1173–1177

    Article  CAS  PubMed  Google Scholar 

  • Hall JM, Couse JF, Korach KS (2001) The multifaceted mechanisms of estradiol and estrogen receptor signaling. J Biol Chem 276:36869–36872

    Article  CAS  PubMed  Google Scholar 

  • Hu L, Gustofson RL, Feng H, Leung PK, Mores N, Krsmanovic LZ, Catt KJ (2008) Converse regulatory functions of estrogen receptor-alpha and -beta subtypes expressed in hypothalamic gonadotropin-releasing hormone neurons. Mol Endocrinol 22:2250–2259

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lenz KM, McCarthy MM (2010) Organized for sex–steroid hormones and the developing hypothalamus. Eur J Neurosci 3:2096–2104

    Article  Google Scholar 

  • Lephart ED (1996) A review of brain aromatase cytochrome P450. Brain Res Rev 22:1–26

    Article  CAS  PubMed  Google Scholar 

  • MacLusky NJ, Naftolin F (1981) Sexual differentiation of the central nervous system. Science 211:1294–1302

    Article  CAS  PubMed  Google Scholar 

  • Mani SK, Mermelstein PG, Tetel MJ, Anesetti G (2012) Convergence of multiple mechanisms of steroid hormone action. Horm Metab Res 44:569–576

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McEwen B (2002) Estrogen actions throughout the brain. Recent Prog Horm Res 57:357–384

    Article  CAS  PubMed  Google Scholar 

  • McGeady TA, Quinn PJ, FitzPatrick ES, Ryan MT (2006) Age determination of embryos and foetus. In: McGeady TA, Quinn PJ, FitzPatrick ES, Ryan MT (eds) Veterinary embryology. Blackwell, Oxford, p 392

    Google Scholar 

  • Melcangi RC, Panzica G, Garcia-Segura LM (2011) Neuroactive steroids: focus on human brain. Neuroscience 191:1–5

    Article  CAS  PubMed  Google Scholar 

  • Mermelstein PG, Micevych PE (2008) Nervous system physiology regulated by membrane estrogen receptors. Rev Neurosci 19:413–424

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Montgomery DC (2004) Design and analysis of experiments, 5th edn. Wiley, New York

    Google Scholar 

  • Morissette M, Le Saux M, D’Astous M, Jourdain S, Al Sweidi S, Morin N, Estrada-Camarena E, Mendez P, Garcia-Segura LM, Di Paolo T (2008) Contribution of estrogen receptors alpha and beta to the effects of estradiol in the brain. J Steroid Biochem Mol Biol 108:327–338

    Article  CAS  PubMed  Google Scholar 

  • Mouriec K, Lareyre JJ, Tong SK, Le Page Y, Vaillant C, Pellegrini E, Pakdel F, Chung BC, Kah O, Anglade I (2009) Early regulation of brain aromatase (cyp19a1b) by estrogen receptors during zebrafish development. Dev Dyn 238:2641–2651

    Article  CAS  PubMed  Google Scholar 

  • Nathanielsz PW, Elsner C, Magyar D, Fridshal D, Freeman A, Buster JE (1982) Time trend analysis of plasma unconjugated and sulfoconjugated estrone and 3 beta-delta 5-steroids in fetal and maternal sheep plasma in relation to spontaneous parturition at term. Endocrinology 110:1402–1407

    Article  CAS  PubMed  Google Scholar 

  • Ohtani-Kaneko R (2006) Mechanisms underlying estrogen-induced sexual differentiation in the hypothalamus. Histol Histopathol 21:317–324

    CAS  PubMed  Google Scholar 

  • Panzica GC, Aste N, Viglietti-Panzica C, Ottinger MA (1995) Structural sex differences in the brain: influence of gonadal steroids and behavioral correlates. J Endocrinol Invest 18:232–252

    Article  CAS  PubMed  Google Scholar 

  • Panzica GC, Viglietti-Panzica C, Balthazart J (1996) The sexually dimorphic medial preoptic nucleus of quail: a key brain area mediating steroid action on male sexual behavior. Front Neuroendocrinol 17:51–125

    Article  CAS  PubMed  Google Scholar 

  • Panzica GC, Aste N, Castagna C, Viglietti-Panzica C, Balthazart J (2001) Steroid-induced plasticity in the sexually dimorphic vasotocinergic innervation of the avian brain: behavioral implications. Brain Res Brain Res Rev 37:178–200

    Article  CAS  PubMed  Google Scholar 

  • Perez SE, Chen EY, Mufson E (2003) Distribution of estrogen receptor alpha and beta 460 immunoreactive profiles in the postnatal rat brain. Brain Res 145:117–139

    Article  CAS  Google Scholar 

  • Peruffo A, Buson G, Cozzi B, Ballarin C (2008a) Primary cell cultures from fetal bovine hypothalamus and cerebral cortex: a reliable model to study P450Arom and ER-α and ER-β estrogen receptors in vitro. Neurosci Lett 434:83–87

    Article  CAS  PubMed  Google Scholar 

  • Peruffo A, Cozzi B, Ballarin C (2008b) Ontogenesis of brain aromatase P450 expression in the bovine hypothalamus. Brain Res Bull 75:60–65

    Article  CAS  PubMed  Google Scholar 

  • Peruffo A, Giacomello M, Montelli S, Corain L, Cozzi B (2011) Expression and localization of aromatase P450AROM, estrogen receptor-α, and estrogen receptor-β in the developing fetal bovine frontal cortex. Gen Comp Endocrinol 172:211–217

    Article  CAS  PubMed  Google Scholar 

  • Pfaff DW, Vasudevan N, Kia HK, Zhu YS, Chan J, Garey J, Morgan M, Ogawa S (2000) Estrogens, brain and behavior: studies in fundamental neurobiology and observations related to women’s health. J Steroid Biochem Mol Biol 74:365–373

    Article  CAS  PubMed  Google Scholar 

  • Pomerantz SM, Fox TO, Sholl SA, Vito CC, Goy RW (1985) Androgen and estrogen receptors in fetal rhesus monkey brain and anterior pituitary. Endocrinology 116:83–89

    Article  CAS  PubMed  Google Scholar 

  • Prewitt AK, Wilson ME (2007) Changes in estrogen receptor-alpha mRNA in the mouse cortex during development. Brain Res 1134:62–69

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Razandi M, Pedram A, Merchenthaler I, Greene GL, Levin ER (2004) Plasma membrane estrogen receptors exist and functions as dimers. Mol Endocrinol 18:2854–2865

    Article  CAS  PubMed  Google Scholar 

  • Richard P (1967) Atlas stéréotaxique du cerveau de Brebis Préalpes du Sud. Institut National de la Recherche Agronomique, Paris

    Google Scholar 

  • Schaub CE, Gersting JA, Keller-Wood M, Wood CE (2008) Development of ER-alpha and ER-beta expression in the developing ovine brain and pituitary. Gene Expr Patterns 8:457–463

    Article  CAS  PubMed  Google Scholar 

  • Sharma PK, Thakur MK (2006) Expression of estrogen receptor (ER) alpha and beta in mouse cerebral cortex: effect of age, sex and gonadal steroids. Neurobiol Aging 27:880–887

    Article  CAS  PubMed  Google Scholar 

  • Sholl SA, Kim KL (1989) Estrogen receptors in the rhesus monkey brain during fetal development. Brain Res Dev Brain Res 50:189–196

    Article  CAS  PubMed  Google Scholar 

  • Shughrue PJ, Lane MV, Merchenthaler I (1997) Comparative distribution of estrogen receptor-α and -β mRNA in the rat central nervous system. J Comp Neurol 388:507–525

    Article  CAS  PubMed  Google Scholar 

  • Tindal JS, Knaggs GS, Turvey A (1968) The forebrain of the goat in stereotaxic coordinates. J Anat 103:457–469

    CAS  PubMed Central  PubMed  Google Scholar 

  • Van Leeuwen FW, Chouham S, Axelson JF, Swaab DF, Van Eerdenburg FJ (1995) Sex differences in the distribution of estrogen receptors in the septal area and hypothalamus of the domestic pig (Sus scrofa). Neuroscience 64:261–275

    Article  PubMed  Google Scholar 

  • Vasudevan N, Pfaff DW (2008) Non-genomic actions of estrogens and their interaction with genomic actions in the brain. Front Neuroendocrinol 29:238–257

    Article  CAS  PubMed  Google Scholar 

  • Welento J, Szteyn S, Milart Z (1969) Observations on the stereotaxic configuration of the hypothalamus nuclei in the sheep. Anat Anz 124:1–27

    CAS  PubMed  Google Scholar 

  • Yamada S, Noguchi D, Ito H, Yamanouchi K (2009) Sex and regional differences in decrease of estrogen receptor alpha-immunoreactive cells by estrogen in rat hypothalamus and midbrain. Neurosci Lett 463:135–139

    Article  CAS  PubMed  Google Scholar 

  • Yoshikawa T (1967) Atlas of the brains of domestic animals. University of Tokyo Press, Tokyo

    Google Scholar 

  • Yu HK, Cabalum T, Jansen CA, Buster JE, Nathanielsz PW (1983) Androstenedione, testosterone, and estradiol concentrations in fetal and maternal plasma in late pregnancy in the sheep. Endocrinology 113:2216–2220

    Article  CAS  PubMed  Google Scholar 

  • Zhao C, Wright KD, Gustafsson J (2008) Estrogen receptor β: an overview and update. Nucl Recept Signal 1:6

    Google Scholar 

  • Zuccolilli GO, Hayashi S, Mori Y (1995) Hypothalamic structures of the goat on stereotaxic coordinates. J Vet Med Sci 57:459–467

    Article  CAS  PubMed  Google Scholar 

Download references

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Panin, M., Corain, L., Montelli, S. et al. Gene expression profiles of estrogen receptors α and β in the fetal bovine hypothalamus and immunohistochemical characterization during development. Cell Tissue Res 359, 619–626 (2015). https://doi.org/10.1007/s00441-014-2023-5

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