Region-specific expression and sex-steroidal regulation on aromatase and its mRNA in the male rat brain: Immunohistochemical and in situ hybridization analyses

Journal of Comparative Neurology

Volumn 500, Issue 3, 2007, Pages 557-573

  Zhao, Changjiu ^a   Fujinaga, Ryutaro ^a   Tanaka, Mayumi ^a   Yanai, Akie ^a   Nakahama, Ken Ichi ^b   Shinoda, Koh ^a  

^a YAMAGUCHI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

Author keywords

Adrenalectomy; Amygdala; Bed nucleus of the stria terminalis; Orchiectomy; Preoptic area

Indexed keywords

ANDROSTANOLONE; AROMATASE; AROMATASE P450; COMPLEMENTARY RNA; ESTRADIOL; ISOENZYME; MESSENGER RNA; SEX HORMONE; TESTOSTERONE; UNCLASSIFIED DRUG;

ADRENALECTOMY; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN NERVE CELL; BRAIN REGION; CELL COUNT; CONTROLLED STUDY; EMBRYO; ENZYME ANALYSIS; ENZYME REGULATION; FEMALE; FETUS; GENE EXPRESSION REGULATION; HORMONAL REGULATION; HORMONE ACTION; IMMUNOCOMPETENT CELL; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDIZATION; MALE; NEWBORN; NONHUMAN; ORCHIECTOMY; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; REGULATORY MECHANISM; RNA ANALYSIS; RNA PROBE; ANIMAL; BRAIN; CELL DIFFERENTIATION; COMPARATIVE STUDY; DRUG EFFECT; ENZYMOLOGY; GENETICS; GROWTH, DEVELOPMENT AND AGING; METABOLISM; NERVE CELL; PHYSIOLOGY; PRENATAL DEVELOPMENT; SEX DIFFERENTIATION; SEXUAL DEVELOPMENT; WISTAR RAT;

ADRENALECTOMY; ANIMALS; AROMATASE; BRAIN; CELL COUNT; CELL DIFFERENTIATION; ESTRADIOL; FEMALE; GONADAL STEROID HORMONES; IMMUNOHISTOCHEMISTRY; MALE; NEURONS; ORCHIECTOMY; RATS; RATS, WISTAR; RNA, MESSENGER; SEX CHARACTERISTICS; SEX DIFFERENTIATION; TESTOSTERONE;

EID: 33846945029     PISSN: 00219967     EISSN: 10969861     Source Type: Journal    
DOI: 10.1002/cne.21193     Document Type: Article

References (95)

1. Abdelgadir SE, Resko JA, Ojeda SR, Lephart ED, McPhaul MJ, Roselli CE. 1994. Androgens regulate aromatase cytochrome P450 messenger ribonucleic acid in rat brain. Endocrinology 135:395-401.
2. Abercrombie M. 1946. Estimation of nuclear population from microtome sections. Anat Rec 94:239-247.
3. Ando S, Canonaco M, Beraldi E, Valenti A, Maggiolini M, Piro A, Tavolaro R, Dessi Fulgheri F. 1988. The evaluation of androgen circulating levels following castration in adult male rats. Exp Clin Endocrinol 91:311-318.
4. Azcoitia I, Sierra A, Veiga S, Honda S, Harada N, Garcia-Segura LM. 2001. Brain aromatase is neuroprotective. J Neurobiol 47:318-329.
5. Balthazart J, Foidart A, Surlemont C, Vockel A, Harada N. 1990. Distribution of aromatase in the brain of the Japanese quail, ring dove, and zebra finch: an immunocytochemical study. J Comp Neurol 301:276-288.
6. Balthazart J, Foidart A, Surlemont C, Harada N. 1991a. Distribution of aromatase-immunoreactive cells in the mouse forebrain. Cell Tissue Res 263:71-79.
7. Balthazart J, Foidart A, Surlemont C, Harada N. 1991b. Neuroanatomical specificity in the co-localization of aromatase and estrogen receptors. J Neurobiol 22:143-157.
8. Balthazart J, Foidart A, Houbart M, Prins GS, Ball GF. 1998. Distribution of androgen receptor-immunoreactive cells in the quail forebrain and their relationship with aromatase immunoreactivity. J Neurobiol 35:323-340.
9. Barnea A, Cho G, George F. 1988. The maturational process of gonadotropin-releasing hormone neurons in the male rat: a role for the adrenal gland in the increase in secretory function. Endocrinology 123:2730-2735.
10. Callard GV, Tchoudakova AV. 1997. Evolutionary and functional significance of two CYP19 genes differentially expressed in brain and ovary of goldfish. J Steroid Biochem Mol Biol 61:387-392.
11. Callard GV, Tchoudakova AV, Kishida M, Wood E. 2001. Differential tissue distribution, developmental programming, estrogen regulation and promoter characteristics of CYP 19 genes in teleost fish. J Steroid Biochem Mol Biol 79:305-314.
12. Chen SA, Besman MJ, Sparkes RS, Zollman S, Klisak I, Mohandas T, Hall PF, Shively JE. 1988. Human aromatase: cDNA cloning, Southern blot analysis, and assignment of the gene to chromosome 15. DNA 7:27-38.
13. Choi I, Troyer DL, Cornwell DL, Kirby-Dobbels KR, Collante WR, Simmen FA. 1997. Closely related genes encode developmental and tissue isoforms of porcine cytochrome P450 aromatase. DNA Cell Biol 16:769-777.
14. Conley A, Corbin J, Simith T, Hinshelwood M, Liu Z, Simpson E. 1997. Porcine aromatases: studies on tissue-specific, functionally distinct isozymes from a single gene? J Steroid Biochem Mol Biol 61:407-413.
15. Cox KH, DeLeon DV, Angerer LM, Angerer RC. 1984. Detection of mRNAs in sea urchin embryos by in situ hybridization using asymmetric RNA probes. Dev Biol 101:485-502.
16. Doody KJ, Lephart ED, Stirling D, Lorence MC, Magness RR, McPhaul MJ, Simpson ER. 1991. Expression of mRNA species encoding steroidogenic enzymes in the rat ovary. J Mol Endocrinol 6:153-162.
17. Fisher CR, Graves KH, Parlow AF, Simpson ER. 1998. Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene. Proc Natl Acad Sci U S A 95:6965-6970.
18. Fujinaga R, Kawano J, Matsuzaki Y, Kamei K, Yanai A, Sheng Z, Tanaka M, Nakahama K, Nagano M, Shinoda K. 2004. Neuroanatomical distribution of Huntingtin-associated protein 1-mRNA in the male mouse brain. J Comp Neurol 478:88-109.
19. Garcia-Segura LM, Wozniak A, Azcoitia I, Rodriguez JR, Hutchison RE, Hutchison JB. 1999. Aromatase expression by astrocytes after brain injury: implications for local estrogen formation in brain repair. Neuroscience 89:567-578.
20. Garcia-Segura LM, Veiga S, Sierra A, Melcangi RC, Azcoitia I. 2003. Aromatase: a neuroprotective enzyme. Prog Neurobiol 71:31-41.
21. Gardner L, Anderson T, Place AR, Dixon B, Elizur A. 2005. Sex change strategy and the aromatase genes. J Steroid Biochem Mol Biol 94:395-404.
22. Gelinas D, Callard GV. 1997. Immunolocalization of aromatase- and androgen receptor-positive neurons in the goldfish brain. Gen Comp Endocrinol 106:155-168.
23. George FW, Ojeda SR. 1982. Changes in aromatase activity in the rat brain during embryonic, neonatal and infantile development. Endocrinology 111:522-529.
24. Guillery RW. 2002. On counting and counting errors. J Comp Neurol 447:1-7.
25. Guillery RW, Herrup K. 1997. Quantification without pontification: choosing a method for counting objects in sectioned tissues. J Comp Neurol 386:2-7.
26. Harada N. 1988. Novel properties of human placental aromatase as cytochrome P-450: purification and characterization of a unique form of aromatase. J Biochem 103:106-113.
27. Harada N, Yamada K, Saito K, Kibe N, Dohmae S, Takagi Y. 1990. Structural characterization of the human estrogen synthetase (aromatase) gene. Biochem Biophys Res Commun 166:365-372.
28. Harada N, Abe-Dohmae S, Loeffen R, Foidart A, Balthazart J. 1993. Synergism between androgens and estrogens in the induction of aromatase and its messenger RNA in the brain. Brain Res 622:243-256.
29. Hickey GJ, Chen SA, Besman MJ, Shivery JE, Hall PF, Gaddy-Kurten D, Richards JS. 1988. Hormonal regulation, tissue distribution, and content of aromatase cytochrome P450 messenger ribonucleic acid and enzyme in rat ovarian follicles and corpora lutea: relationship to estradiol biosynthesis. Endocrinology 122:1426-1436.
30. Hickey GJ, Krasnow JS, Beattie WG, Richards JS. 1990. 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 4:3-12.
31. Hutchison JB, Steimer T. 1986. Formation of behaviorally effective 17β-estradiol in the dove brain: steroid control of preoptic aromatase. Endocrinology 118:2180-2187.
32. Hutchison JB, Steimer T, Hutchison RE. 1991. Area-specific hormonal regulation of brain aromatase. Brain Res 550:95-100.
33. Jakab RL, Horvath TL, Leranth C, Harada N, Naftolin F. 1993. Aromatase immunoreactivity in the rat brain: gonadectomy-sensitive hypothalamic neurons and an unresponsive "limbic ring" of the lateral septumbed nucleus-amygdala complex. J Steroid Biochem Mol Biol 44:481-498.
34. Jakab RL, Harada N, Naftolin F. 1994. Aromatase (estrogen synthetase)-immunoreactive neurons in the rat septal area. A light and electron microscopic study. Brain Res 664:85-93.
35. Kitawaki J, Osawa Y, Callard GV. 1987. Aromatase isozyme in goldfish brain and stereochemistry of the aromatization. Steroids 50:637-638.
36. Kitawaki J, Yoshida N, Osawa Y. 1989. An enzyme-linked immunosorbent assay for quantitation of aromatase cytochrome P-450. Endocrinology 124:1417-1423.
37. Lahbib-Mansais Y, Barbosa A, Yerle M, Parma P, Milan D, Pailhoux E, Gellin J, Cotinot C. 1997. Mapping in pig of genes involved in sexual differentiation: AMH, WT1, FTZF1, SOX2, SOX9, AHC, and placental and embryonic CYP19. Cytogenet Cell Genet 76:109-114.
38. Lauber ME, Lichtensteiger W. 1994. Pre- and postnatal ontogeny of aromatase cytochrome P450 messenger ribonucleic acid expression in the male rat brain studied by in situ hybridization. Endocrinology 135:1661-1668.
39. Lauber ME, Sarasin A, Lichtensteiger W. 1997. Transient sex differences of aromatase (CYP19) mRNA expression in the developing rat brain. Neuroendocrinology 66:173-180.
40. Lephart ED, Peterson KG, Noble JF, George FW, McPhaul MJ. 1990. The structure of cDNA clones encoding the aromatase P-450 isolated from a rat Leydig cell tumor line demonstrates differential processing of aromatase mRNA in rat ovary and a neoplastic cell line. Mol Cell Endocrinol 70:31-40.
41. MacLusky NJ, Naftolin F. 1981. Sexual differentiation of the central nervous system. Science 211:1294-1302.
42. Mahendroo MS, Means GD, Mendelson CR, Simpson ER. 1991. Tissue-specific expression of human P-450AROM. The promoter responsible for expression in adipose tissue is different from that utilized in placenta. J Biol Chem 266:11276-11281.
43. McCullough LD, Blizzard K, Simpson ER, Oz OK, Hurn PD. 2003. Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection. J Neurosci 23:8701-8705.
44. McEwen BS, Lieberburg I, Chaptal C, Krey LC. 1977. Aromatization: important for sexual differentiation of the neonatal rat brain. Horm Behav 9:249-263.
45. Means GD, Mahendroo MS, Corbin CJ, Mathis JM, Powell FE, Mendelson CR, Simpson ER. 1989. Structural analysis of the gene encoding human aromatase cytochrome P-450, the enzyme responsible for estrogen biosynthesis. J Biol Chem 264:19385-19391.
46. Naftolin F, Ryan KJ, Petro Z. 1971. Aromatization of androstenedione by the diencephalon. J Clin Endocrinol Metab 33:368-370.
47. Naftolin F, Ryan KJ, Petro Z. 1972. Aromatization of androstenedione by the anterior hypothalamus of adult male and female rats. Endocrinology 90:295-298.
48. Naftolin F, Ryan KJ, Davies IJ, Reddy VV, Flores F, Petro Z, Kuhn M, White RJ, Takaoka Y, Wolin L. 1975. The formation of estrogens by central neuroendocrine tissues. Rec Prog Horm Res 31:295-319.
49. Osawa Y, Yoshida N, Fronckowiak M, Kitawaki J. 1987. Immunoaffinity purification of aromatase cytochrome P-450 from human placental microsomes. Metabolic switching from aromatization to 1β- and 2β-monohydroxylation and recognition of aromatase isozymes. Steroids 50:11-28.
50. Pasmanik M, Schlinger BA, Callard GV. 1988. In vivo steroid regulation of aromatase and 5α-reductase in goldfish brain and pituitary. Gen Comp Endocrinol 71:175-182.
51. Paxinos G, Watson C. 1998. The rat brain in stereotaxic coordinates, 4th ed. San Diego: Academic Press.
52. Reddy VVR, Naftolin F, Ryan KJ. 1973. Aromatization in the central nervous system of rabbits: effects of castration and hormone treatment. Endocrinology 92:589-594.
53. Resko JA, Pereyra-Martinez AC, Stadelman HL, Roselli CE. 2000. Region-specific regulation of cytochrome P450 aromatase messenger ribonucleic acid by androgen in brains of male rhesus monkeys. Biol Reprod 62:1818-1822.
54. Roselli CE. 1991. Synergistic induction of aromatase activity in the rat brain by estradiol and 5α-dihydrotestosterone. Neuroendocrinology 53:79-84.
55. Roselli CE, Resko JA. 1984. Androgens regulate brain aromatase activity in adult male rats through a receptor mechanism. Endocrinology 114:2183-2189.
56. Roselli CE, Resko JA. 1987. The distribution and regulation of aromatase activity in the central nervous system. Steroids 50:495-508.
57. Roselli CE, Horton LE, Resko JA. 1985. Distribution and regulation of aromatase activity in the rat hypothalamus and limbic system. Endocrinology 117:2471-2477.
58. Roselli CE, Horton LE, Resko JA. 1987a. Time-course and steroid specificity of aromatase induction in rat hypothalamus-preoptic area. Biol Reprod 37:628-633.
59. Roselli CE, Salisbury RL, Resko JA. 1987b. Genetic evidence for androgen-dependent and independent control of aromatase activity in the rat brain. Endocrinology 121:2205-2210.
60. Roselli CE, Klosterman SA, Fasasi TA. 1996. Sex differences in androgen responsiveness in the rat brain: regional differences in the induction of aromatase activity. Neuroendocrinology 64:139-145.
61. Roselli CE, Abdelgadir SE, Resko JA. 1997. Regulation of aromatase gene expression in the adult rat brain. Brain Res Bull 44:351-357.
62. Roselli CE, Abdelgadir SE, Ronnekleiv OK, Klosterman SA. 1998. Anatomic distribution and regulation of aromatase gene expression in the rat brain. Biol Reprod 58:79-87.
63. Roselli CE, Stormshak F, Resko JA. 2000. Distribution of aromatase mRNA in the ram hypothalamus: an in situ hybridization study. J Neuroendocrinol 12:656-664.
64. Roselli CE, Klosterman S, Resko JA. 2001. Anatomic relationships between aromatase and androgen receptor mRNA expression in the hypothalamus and amygdala of adult male cynomolgus monkeys. J Comp Neurol 439:208-223.
65. Saleh TM, Connell BJ, Legge C, Cribb AE. 2005. Estrogen synthesis in the central nucleus of the amygdala following middle cerebral artery occlusion: Role in modulating neurotransmission. Neuroscience 135:1141-1153.
66. Sanghera MK, Simpson ER, McPhaul MJ, Kozlowski G, Conley AJ, Lephart ED. 1991. Immunocytochemical distribution of aromatase cytochrome P450 in the rat brain using peptide-generated polyclonal antibodies. Endocrinology 129:2834-2844.
67. Selmanoff MK, Brodkin LD, Weiner RI, Siiteri PK. 1977. Aromatization and 5α-reduction of androgens in discrete hypothalamic and limbic regions of the male and female rats. Endocrinology 101:841-848.
68. Sheng Z, Yanai A, Fujinaga R, Kawano J, Tanaka M, Watanabe Y, Shinoda K. 2003. Gonadal and adrenal effects on the glucocorticoid receptor in the rat hippocampus, with special reference to regulation by estrogen from an immunohistochemical view-point. Neurosci Res 46:205-218.
69. Sheng Z, Kawano J, Yanai A, Fujinaga R, Tanaka M, Watanabe Y, Shinoda K. 2004. Expression of estrogen receptors (α, β) and androgen receptor in serotonin neurons of the rat and mouse dorsal raphe nuclei; sex and species differences. Neurosci Res 49:185-196.
70. Shinoda K. 1994a. Brain aromatization and its associated structures. Endocr J 41:115-138.
71. Shinoda K. 1994b. Sex-steroid receptor mechanism related to neuronal aromatase and the stigmoid body. Horm Behav 28:545-555.
72. Shinoda K. 1996. A critical role of neural aromatase in brain sexual differentiation. Brain Med 8:253-279.
73. Shinoda K. 1998. A new concept for brain aromatase in sexual differentiation. The 14th TMIN International Symposium, Tokyo. p 36-38.
74. Shinoda K, Yagi H, Fujita H, Osawa Y, Shiotani Y. 1989. Screening of aromatase-containing neurons in rat forebrain: an immunohistochemical study with antibody against human placental antigen X-P2 (hPAX-P2). J Comp Neurol 290:502-515.
75. Shinoda K, Mori S, Ohtsuki T, Osawa Y. 1992. An aromatase-associated cytoplasmic inclusion, the "stigmoid body," in the rat brain: I. Distribution in the forebrain. J Comp Neurol 322: 360-376.
76. Shinoda K, Nagano M, Osawa Y. 1994. Neuronal aromatase expression in preoptic, strial, and amygdaloid regions during late prenatal and early postnatal development in the rat. J Comp Neurol 343:113-129.
77. Shinoda, K, Lei H, Yoshii H, Nomura M, Nagano M, Shiba H, Sasaki H, Osawa Y, Ninomiya Y, Niwa O, Morohashi K, Li E. 1995. Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz-F1 disrupted mice. Dev Dyn 204:22-29.
78. Shinoda K, Nagano M, Nakahama K, Sasaki H. 1996. Distribution of aromatase-immunoreactive neurons in the monkey forebrain [abstract]. Acta Anat Nipp 71:462 (3D03).
79. Simpson ER. 2000. Role of aromatase in sex steroid action. J Mol Endocrinol 25:149-156.
80. Simpson ER. 2003. Sources of estrogen and their importance. J Steroid Biochem Mol Biol 86:225-230.
81. Swanson LW. 2004. Brain maps III: structure of the rat brain. San Diego: Academic Press.
82. Tanaka M, Fujinaga R, Sheng Z, Shinoda K. 2001. Expression of estrogen receptor β in aromatase-immunoreactive (AROM-I) neurons in the neonatal and adult male rat brains. Neurosci Res Suppl 25:S147.
83. Tchoudakova A, Callard GV. 1998. Identification of multiple CYP19 genes encoding different cytochrome P450 aromatase isozymes in brain and ovary. Endocrinology 139:2179-2189.
84. Toda K, Terashima M, Kawamoto T, Sumimoto H, Yokoyama Y, Kuribayashi I, Mitsuuchi Y, Maeda T, Yamamoto Y, Sagara Y. 1990. Structural and functional characterization of human aromatase P-450 gene. Eur J Biochem 193:559-565.
85. Toda K, Takeda K, Okada T, Akira S, Saibara T, Kaname T, Yamamura K, Onishi S, Shizuta Y. 2001. Targeted disruption of the aromatase P450 gene (Cyp19) in mice and their ovarian and uterine responses to 17β-estradiol. J Endocrinol 170:99-111.
86. Tsuruo Y, Ishimura K, Fujita H, Osawa Y. 1994. Immunocytochemical localization of aromatase-containing neurons in the rat brain during pre- and postnatal development. Cell Tissue Res 278:29-39.
87. Tsuruo Y, Ishimura K, Osawa Y. 1995. Presence of estrogen receptors in aromatase-immunoreactive neurons in the mouse brain. Neurosci Lett 195:49-52.
88. Tsuruo Y, Ishimura K, Hayashi S, Osawa Y. 1996. Immunohistochemical localization of estrogen receptors within aromatase-immunoreactive neurons in the fetal and neonatal rat brain. Anat Embryol 193:115-121.
89. Veney SL, Rissman EF. 2000. Immunolocalization of androgen receptors and aromatase enzyme in the adult musk shrew brain. Neuroendocrinology 72:29-36.
90. Wagner CK, Morrell JI. 1996. Distribution and steroid hormone regulation of aromatase mRNA expression in the forebrain of adult male and female rats: a cellular-level analysis using in situ hybridization. J Comp Neurol 370:71-84.
91. Wagner CK, Morrell JI. 1997. Neuroanatomical distribution of aromatase mRNA in the rat brain: indications of regional regulation. J Steroid Biochem Mol Biol 61:307-314.
92. Washida N, Matsui S, Osawa Y. 1985. Preparation of monoclonal antibody against human placental aromatase II cytochrome P-450 [abstract]. Fed Proc 44:861.
93. Weisz J, Gibbs C. 1974. Conversion of testosterone and androstenedione to estrogens in vitro by the brain of female rats. Endocrinology 94:616-620.
94. Yeh S, Miyamoto H, Shima H, Chang C. 1998. From estrogen to androgen receptor: a new pathway for sex hormones in prostate. Proc Natl Acad Sci U S A 95:5527-5532.
95. Yuan H, Bowlby DA, Brown TJ, Hochberg RB, MacLusky NJ. 1995. Distribution of occupied and unoccupied estrogen receptors in the rat brain: effects of physiological gonadal steroid exposure. Endocrinology 136:96-105.