Brain aromatization: Classic roles and new perspectives

Seminars in Reproductive Medicine

Volumn 27, Issue 3, 2009, Pages 207-217

  Roselli, Charles E ^a,b   Liu, Mingyue ^b   Hurn, Patricia D ^a,b  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

Brain ischemia; CYP19; Cytochrome P450 aromatase; LH; Sexual behavior; Sexual partner preference

Indexed keywords

AROMATASE; ESTRADIOL; GONADORELIN; GONADOTROPIN; LUTEINIZING HORMONE; TESTOSTERONE;

AROMATIZATION; BRAIN FUNCTION; HORMONE RELEASE; HUMAN; NEUROPHYSIOLOGY; NEUROPROTECTION; NONHUMAN; ONTOGENY; PROTEIN EXPRESSION; REVIEW; SEX DIFFERENTIATION; SEXUAL BEHAVIOR;

ANIMALS; AROMATASE; BRAIN; ESTRADIOL; FEMALE; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GONADOTROPINS; HUMANS; MALE; NERVOUS SYSTEM DISEASES; PHOSPHORYLATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; SEX DIFFERENTIATION; SEXUAL BEHAVIOR, ANIMAL; SEXUAL DEVELOPMENT; STROKE; TESTOSTERONE;

EID: 67649649620     PISSN: 15268004     EISSN: 15264564     Source Type: Journal    
DOI: 10.1055/s-0029-1216274     Document Type: Review

References (138)

1. Naftolin F, Ryan KJ, Davies IJ, et al. The formation of estrogens by central neuroendocrine tissues. Recent Prog Horm Res 1975;31:295-319
2. Naftolin F. Brain aromatization of androgens. J Reprod Med 1994;39:257-261 (Pubitemid 24125864)
3. Lephart ED. A review of brain aromatase cytochrome P450. Brain Res Brain Res Rev 1996;22:1-26
4. Roselli CE, Abdelgadir SE, Ronnekleiv OK, Klosterman SA. Anatomic distribution and regulation of aromatase gene expression in the rat brain. Biol Reprod 1998;58: 79-87 (Pubitemid 28023735)
5. Naftolin F, Ryan KJ, Davies IJ, et al. The formation of estrogens by central neuroendocrine tissues. Recent Prog Horm Res 1975;31:295-319
6. Abdelgadir SE, Resko JA, Ojeda SR, Lephart ED, McPhaul MJ, Roselli CE. Androgens regulate aromatase cytochrome P450 messenger ribonucleic acid in rat brain. Endocrinology 1994;135:395-401 (Pubitemid 24203843)
7. Roselli CE, Horton LE, Resko JA. Distribution and regulation of aromatase activity in the rat hypothalamus and limbic system. Endocrinology 1985;117:2471-2477 (Pubitemid 16194078)
8. Simerly RB, Chang C, Muramatsu M, Swanson LW. The distribution of androgen and estrogen receptor mRNAcontaining cells in the rat brain: an in situ hybridization study. J Comp Neurol 1990;294:76-95 (Pubitemid 20104631)
9. Hojo Y, Hattori TA, Enami T, et al. Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes P45017α and P450 aromatase localized in neurons. Proc Natl Acad Sci U S A 2004;101:865-870 (Pubitemid 38121049)
10. MacLusky NJ, Walters MJ, Clark AS, Toran-Allerand CD. Aromatase in the cerebral cortex, hippocampus, and midbrain: ontogeny and developmental implications. Mol Cell Neurosci 1994;5:691-698
11. Evrard HC. Estrogen synthesis in the spinal dorsal horn: a new central mechanism for the hormonal regulation of pain. Am J Physiol Regul Integr Comp Physiol 2006;291:R291-R299 (Pubitemid 44035634)
12. Stoffel-Wagner B, Watzka M, Schramm J, Bidlingmaier F, Klingmuller D. Expression of CYP19 (aromatase) mRNA in different areas of the human brain. J Steroid Biochem Mol Biol 1999;70:237-241 (Pubitemid 29528435)
13. Horvath TL, Wikler KC. Aromatase in developing sensory systems of the rat brain. J Neuroendocrinol 1999;11:77-84 (Pubitemid 29056002)
14. Lavaque E, Mayen A, Azcoitia I, Tena-Sempere M, Garcia-Segura LM. Sex differences, developmental changes, response to injury and cAMP regulation of the mRNA levels of steroidogenic acute regulatory protein, cytochrome p450scc, and aromatase in the olivocerebellar system. J Neurobiol 2006;66:308-318 (Pubitemid 43202767)
15. Kretz O, Fester L, Wehrenberg U, et al. Hippocampal synapses depend on hippocampal estrogen synthesis. J Neurosci 2004;24:5913-5921 (Pubitemid 38859389)
16. Tanapat P, Hastings NB, Gould E. Ovarian steroids influence cell proliferation in the dentate gyrus of the adult female rat in a dose- and time-dependent manner. J Comp Neurol 2005;481:252-265 (Pubitemid 40023535)
17. Naftolin F, Horvath TL, Jakab RL, Leranth C, Harada N, Balthazart J. Aromatase immunoreactivity in axon terminals of the vertebrate brain - an immunocytochemical study on quail, rat, monkey and human tissues. Neuroendocrinology 1996;63:149-155 (Pubitemid 26049626)
18. Peterson RS, Yarram L, Schlinger BA, Saldanha CJ. Aromatase is pre-synaptic and sexually dimorphic in the adult zebra finch brain. Proc Biol Sci 2005;272:2089-2096 (Pubitemid 41416045)
19. Veney SL, Rissman EF. Co-localization of estrogen receptor and aromatase enzyme immunoreactivities in adult musk shrew brain. Horm Behav 1998;33:151-162 (Pubitemid 28376169)
20. Tsuruo Y, Ishimura K, Hayashi S, Osawa Y. Immunohistochemical localization of estrogen receptors within aromatase-ummunoreactive neurons in the fetal and neonatal rat brain. Anat Embryol (Berl) 1996;193:115-121 (Pubitemid 26040026)
21. Balthazart J, Foidart A, Surlemont C, Harada N. Neuroanatomical specificity in the co-localization of aromatase and estrogen receptors. J Neurobiol 1991;22:143-157
22. Ronnekleiv OK, Malyala A, Kelly MJ. Membrane-initiated signaling of estrogen in the brain. Semin Reprod Med 2007;25:165-177 (Pubitemid 46676903)
23. Balthazart J, Ball GF. Is brain estradiol a hormone or a neurotransmitter? Trends Neurosci 2006;29:241-249
24. Martinez-Cerdeno V, Noctor SC, Kriegstein AR. Estradiol stimulates progenitor cell division in the ventricular and subventricular zones of the embryonic neocortex. Eur J Neurosci 2006;24:3475-3488 (Pubitemid 44952613)
25. Götz M, Barde YA. Radial glial cells: defined and major intermediates between embryonic stem cells and CNS neurons. Neuron 2005;46:369-372 (Pubitemid 40616877)
26. Mouriec K, Pellegrini E, Anglade I, et al. Synthesis of estrogens in progenitor cells of adult fish brain: evolutive novelty or exaggeration of a more general mechanism implicating estrogens in neurogenesis? Brain Res Bull 2008; 75:274-280
27. Yague JG, Munoz A, Monasterio-Schrader P, DeFelipe J, Garcia-Segura LM, Azcoitia I. Aromatase expression in the human temporal cortex. Neuroscience 2006;138: 389-401 (Pubitemid 43255552)
28. Yague JG, Wang ACJ, Janssen WGM, et al. Aromatase distribution in the monkey temporal neocortex and hippocampus. Brain Res 2008;1209:115-127
29. Garcia-Segura LM, Wozniak A, Azcoitia I, Rodriguez JR, Hutchison RE, Hutchison JB. Aromatase expression by astrocytes after brain injury: implications for local estrogen formation in brain repair. Neuroscience 1999;89:567-578 (Pubitemid 29044337)
30. Peterson RS, Saldanha CJ, Schlinger BA. Rapid upregulation of aromatase mRNA and protein following neural injury in the zebra finch (Taeniopygia guttata). J Neuroendocrinology 2001;13:317-323 (Pubitemid 32237003)
31. Carswell HVO, Dominiczak AF, Garcia-Segura LM, Harada N, Hutchison JB, Macrae IM. Brain aromatase expression after experimental stroke: topography and time course. J Steroid Biochem Mol Biol 2005;96:89-96 (Pubitemid 41080522)
32. McCullough LD, Blizzard K, Simpson ER, Oz OK, Hurn PD. Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection. J Neurosci 2003;23: 8701-8705 (Pubitemid 37176650)
33. Wynne RD, Walters BJ, Bailey DJ, Saldanha CJ. Inhibition of injury-induced glial aromatase reveals a wave of secondary degeneration in the songbird brain. Glia 2008;56:97-105 (Pubitemid 350172735)
34. Hoyk Z, Parducz A, Garcia-Segura LM. Dehydroepiandrosterone regulates astroglia reaction to denervation of olfactory glomeruli. Glia 2004;48:207-216 (Pubitemid 39545936)
35. Azcoitia I, Sierra A, Garcia-Segura LM. Aromatase expression by reactive astroglia is neuroprotective. Ann N Y Acad Sci 2003;1007:298-305 (Pubitemid 38253675)
36. Garcia-Segura LM, Veiga S, Sierra A, Melcangi RC, Azcoitia I. Aromatase: a neuroprotective enzyme. Prog Neurobiol 2003;71:31-41 (Pubitemid 37377933)
37. Wynne RD, Saldanha CJ. Glial aromatization decreases neural injury in the zebra finch (Taeniopygia guttata): influence on apoptosis. J Neuroendocrinol 2004;16:676-683 (Pubitemid 39162724)
38. Balthazart J, Ball GF. New insights into the regulation and function of brain estrogen synthetase (aromatase). Trends Neurosci 1998;21:243-249 (Pubitemid 28239981)
39. MacLusky NJ, Naftolin F. Sexual differentiation of the central nervous system. Science 1981;211:1294-1302 (Pubitemid 11097283)
40. Lauber ME, Lichtensteiger W. Pre- and postnatal ontogeny of aromatase cytochrome P450 messenger ribonucleic acid expression in the male rat brain studied by in situ hybridization. Endocrinology 1994;135:1661-1668 (Pubitemid 24307547)
41. Zhao C, Fujinaga R, Tanaka M, Yanai A, Nakahama K, Shinoda K. Region-specific expression and sex-steroidal regulation on aromatase and its mRNA in the male rat brain: immunohistochemical and in situ hybridization analyses. J Comp Neurol 2007;500:557-573 (Pubitemid 46252677)
42. Connolly PB, Roselli CE, Resko JA. Aromatase activity in developing guinea pig brain: ontogeny and effects of exogenous androgens. Biol Reprod 1994;50:436-441 (Pubitemid 24058500)
43. Roselli CE, Resko JA. Effects of gonadectomy and androgen treatment on aromatase acitivity in the fetal monkey brain. Biol Reprod 1986;35:106-112 (Pubitemid 17192319)
44. Roselli CE, Resko JA, Stormshak F. Estrogen synthesis in fetal sheep brain: effect of maternal treatment with an aromatase inhibitor. Biol Reprod 2003;68:370-374 (Pubitemid 36139300)
45. Peruffo A, Cozzi B, Ballarin C. Ontogenesis of brain aromatase P450 expression in the bovine hypothalamus. Brain Res Bull 2008;75:60-65 (Pubitemid 350297642)
46. Wallen K, Baum MJ. Masculinization and defeminization in altricial and precocial mammals: comparative aspects of steroid hormone actionIn: Pfaff DW, Arnold AP, Etgen AM, Fahrbach SE, Rubin RTHormones, Brain and Behavior. San Diego, CA. Elsevier Science; 2002:385-423
47. Forger NG, Rosen GJ,Waters EM, Jacob D, Simerly RB, de Vries GJ. Deletion of Bax eliminates sex differences in the mouse forebrain. Proc Natl Acad Sci U S A 2004;101:13666-13671 (Pubitemid 39238460)
48. Toran-Allerand CD. Sex steroids and the development of the newborn mouse hypothalamus and preoptic area in vitro: implication for sexual differentiation. Brain Res 1976;106: 407-412
49. Roselli CE, Resko JA. Sex differences in androgen-regulated expression of cytochrome P450 aromatase in the rat brain. J Steroid Biochem Mol Biol 1997;61:365-374 (Pubitemid 27459891)
50. Balthazart J, Baillien M, Charlier TD, Cornil CA, Ball GF. Multiple mechanisms control brain aromatase activity at the genomic and non-genomic level. J Steroid Biochem Mol Biol 2003;86:367-379 (Pubitemid 37420004)
51. Callard GV, Tchoudakova AV, Kishida M, Wood E. Differential tissue distribution, developmental programming, estrogen regulation and promoter characteristics of cyp19 genes in teleost fish. J Steroid Biochem Mol Biol 2001;79: 305-314 (Pubitemid 34158806)
52. Roselli CE, Resko JA. Cytochrome P450 aromatase (CYP19) in the non-human primate brain: distribution, regulation, and functional significance. J Steroid Biochem Mol Biol 2001;79:247-253 (Pubitemid 34158801)
53. Veney SL, Rissman EF. Immunolocalization of androgen receptors and aromatase enzyme in the adult musk shrew brain. Neuroendocrinology 2000;72:29-36 (Pubitemid 30665971)
54. Honda S, Harada N, Takagi Y. Novel exon 1 of the aromatase gene specific for aromatase transcripts in human brain. Biochem Biophys Res Commun 1994;198:1153-1160 (Pubitemid 24172817)
55. Reddy VVR, Naftolin F, Ryan KJ. Aromatization in the central nervous system of rabbits: effects of castration and hormone treatment. Endocrinology 1973;92:589-594
56. Roselli CE. Synergistic induction of aromatase activity in the rat brain by estradiol and 5α-dihydrotestosterone. Neuroendocrinology 1991;53:79-84
57. Gardner L, Anderson T, Place AR, Dixon B, Elizur A. Sex change strategy and the aromatase genes. J Steroid Biochem Mol Biol 2005;94:395-404 (Pubitemid 40616401)
58. Bulun SE, Sebastian S, Takayama K, Suzuki T, Sasano H, Shozu M. The human CYP19 (aromatase P450) gene: update on physiologic roles and genomic organization of promoters. J Steroid Biochem Mol Biol 2003;86:219-224 (Pubitemid 37412560)
59. Sasano H, Takahashi K, Satoh F, Nagura H, Harada N. Aromatase in the human central nervous system. Clin Endocrinol (Oxf) 1998;48:325-329 (Pubitemid 28137645)
60. Kato J, Yamada-Mouri N, Hirata S. Structure of aromatase mRNA in the rat brain. J Steroid Biochem Mol Biol 1997; 61:381-385 (Pubitemid 27455699)
61. Cornil CA, Ball GF, Balthazart J. Functional significance of the rapid regulation of brain estrogen action: where do the estrogens come from? Brain Res 2006;1126:2-26
62. Cooke B, Hegstrom CD, Villeneuve LS, Breedlove SM. Sexual differentiation of the vertebrate brain: principles and mechanisms. Front Neuroendocrinol 1998;19:323-362 (Pubitemid 28487799)
63. Bakker J, Baum MJ. Role for estradiol in female-typical brain and behavioral sexual differentiation. Front Neuroendocrinol 2008;29:1-16
64. Karsch FJ, Dierschke DJ, Knobil E. Sexual differentiation of pituitary function: apparent difference between primates and rodents. Science 1973;179:484-486
65. McEwen BS, Lieberburg I, Chaptal C, Krey LC. Aromatization: important for sexual differentiation of the neonatal rat brain. Horm Behav 1977;9:249-263 (Pubitemid 8292758)
66. Vreeburg JTM, van der Vaart PDM, Van Der Schoot P. Prevention of central defeminization but not masculinization in male rats by inhibition neonatally of oestrogen biosynthesis. J Endocrinol 1977;74:375-382 (Pubitemid 8185877)
67. Baum MJ, Carroll RS, Tobet SA. Steroidal control of behavioural, neuroendocrine and brain sexual differentiation: studies in a carnivore, the ferret. J Neuroendocrinol 1990;2:401-418 (Pubitemid 20325988)
68. Roselli CE, Schrunk JM, Stadelman HL, Resko JA, Stormshak F. The effect of aromatase inhibition on the sexual differentiation of the sheep brain. Endocrine 2006;29: 501-512 (Pubitemid 44358841)
69. Gorski RA, Gordon JH, Shryne JE, Southam AM. Evidence for a morphological sex difference within the medial preoptic area or the rat brain. Brain Res 1978;148: 333-346 (Pubitemid 8341403)
70. Dohler KD, Coquelin A, Davis F, Hines M, Shryne JE, Gorski RA. Pre- and postnatal influence of testosterone propionate and diethylstilbestrol on differentiation of the sexually dimorphic nucleus of the preoptic area in male and female rats. Brain Res 1984;302:291-295 (Pubitemid 14077757)
71. Houtsmuller EJ, Brand T, De Jonge FH, Joosten RNJMA, Van De Poll NE, Slob AK. SDN-POA volume, sexual behavior, and partner preference of male rats affected by perinatal treatment with ATD. Physiol Behav 1994;56:535-541 (Pubitemid 24269577)
72. Schwarz JM, McCarthy MM. Cellular mechanisms of estradiol-mediated masculinization of the brain. J Steroid Biochem Mol Biol 2008;109:300-306
73. Simerly RB. Wired for reproduction: organization and development of sexually dimorphic circuits in the mammalian forebrain. Annu Rev Neurosci 2002;25:507-536 (Pubitemid 34748027)
74. Arendash GW, Gorski RA. Effects of discrete lesions of the sexually dimorphic nucleus of the preoptic area or other medial preoptic regions on the sexual behavior of male rats. Brain Res Bull 1983;10:147-154 (Pubitemid 13193428)
75. De Jonge FH, Louwerse AL, Ooms MP, Evers P, Endert E, Van De Poll NE. Lesions of the SDN-POA inhibit sexual behavior of maleWistar rats. Brain Res Bull 1989;23: 483-492 (Pubitemid 20035314)
76. Paredes RG, Baum MJ. Altered sexual partner preference in male ferrets given excitotoxic lesions of the preoptic area anterior hypothalamus. J Neurosci 1995;15:6619-6630
77. Paredes RG, Nakagawa Y, Nakach N. Lesions of the medial preoptic area/anterior hypothalamus (MPOA/AH) modify partner preference in male rats. Brain Res 1998;813:1-8 (Pubitemid 29012510)
78. Vasey PL. Same-sex sexual partner preference in hormonally and neurologically unmanipulated animals. Annu Rev Sex Res 2002;13:141-179 (Pubitemid 41755055)
79. Perkins A, Roselli CE. The ram as a model for behavioral neuroendocrinology. Horm Behav 2007;52:70-77 (Pubitemid 46809865)
80. Roselli CE, Larkin K, Resko JA, Stellflug JN, Stormshak F. The volume of a sexually dimorphic nucleus in the ovine medial preoptic area/anterior hypothalamus varies with sexual partner preference. Endocrinology 2004;145:478-483 (Pubitemid 38183788)
81. Roselli CE, Stadelman H, Reeve R, Bishop CV, Stormshak F. The ovine sexually dimorphic nucleus of the medial preoptic area is organized prenatally by testosterone. Endocrinology 2007;148:4450-4457 (Pubitemid 47295693)
82. LeVay S. A difference in hypothalamic structure between heterosexual and homosexual men. Science 1991;253:1034-1037 (Pubitemid 21917252)
83. Adkins-Regan E, Mansukhani V, Thompson R, Yang S. Organizational actions of sex hormones on sexual partner preference. Brain Res Bull 1997;44:497-502 (Pubitemid 27467297)
84. Brand T, Kroonen J, Mos J, Slob AK. Adult partner preference and sexual behavior of male rats affected by perinatal endocrine manipulations. Horm Behav 1991;25: 323-341
85. Bakker J, Honda S, Harada N, Balthazart J. Sexual partner preference requires a functional aromatase (Cyp 19) gene in male mice. Horm Behav 2002;42:158-171 (Pubitemid 35304448)
86. Resko JA, Perkins A, Roselli CE, Fitzgerald JA, Choate JVA, Stormshak F. Endocrine correlates of partner preference behavior in rams. Biol Reprod 1996;55:120-126 (Pubitemid 26293148)
87. Carani C, Qin K, Simoni M, et al. Effect of testosterone and estradiol in a man with aromatase deficiency. N Engl J Med 1997;337:91-95 (Pubitemid 27284394)
88. Carani C, Granata ARM, Rochira V, et al. Sex steroids and sexual desire in a man with a novel mutation of aromatase gene and hypogonadism. Psychoneuroendocrinology 2005; 30:413-417 (Pubitemid 40249807)
89. DuPree MG, Mustanski BS, Bocklandt S, Nievergelt C, Hamer DH. A candidate gene study of CYP19 (aromatase) and male sexual orientation. Behav Genet 2004;34:243-250 (Pubitemid 38437621)
90. Hull EM, Meisel RL, Sachs BD. Male sexual behavior. In: Pfaff DW, Arnold AP, Etgen AM, Fahrbach SE, Rubin RT, eds. Hormones, Brain and Behavior. San Diego, CA: Academic Press; 2002:3-137
91. Sodersten P. Estrogen-activated sexual behavior in male rats. Horm Behav 1973;4:247-256
92. Bonsall RW, Clancy AN, Michael RP. Effects of the nonsteroidal aromatase inhibitor, fadrozole, on sexual behavior in male rats. Horm Behav 1992;26:240-254
93. Vagell ME, McGinnis MY. The role of aromatization in the restoration of male rat reproductive behavior. J Neuroendocrinol 1997;9:415-421 (Pubitemid 27248275)
94. Beyer C, Morali G, Naftolin F, Larsson K, Perez-Palacios G. Effect of some antiestrogens and aromatase inhibitors on androgen induced sexual behavior in castrated male rats. Horm Behav 1976;7:353-363
95. Roselli CE, Cross E, Poonyagariyagorn HK, Stadelman HL. Role of aromatization in anticipatory and consummatory aspects of sexual behavior in male rats. Horm Behav 2003;44:146-151 (Pubitemid 37108637)
96. Fisher CR, Graves KH, Parlow AF, Simpson ER. Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp 19 gene. Proc Natl Acad Sci U S A 1998;95:6965-6970 (Pubitemid 28278090)
97. Honda S, Harada N, Ito S, Takagi Y, Maeda S. Disruption of sexual behavior in male aromatase-deficient mice lacking exons 1 and 2 of the cyp19 gene. Biochem Biophys Res Commun 1998;252:445-449 (Pubitemid 28542906)
98. Toda K, Okada T, Takeda K, et al. Oestrogen at the neonatal stage is critical for the reproductive ability of male mice as revealed by supplementation with 17beta-oestradiol to aromatase gene (Cyp19) knockout mice. J Endocrinol 2001;168:455-463 (Pubitemid 32241890)
99. Matsumoto T, Honda S, Harada N. Alteration in sexspecific behaviors in male mice lacking the aromatase gene. Neuroendocrinology 2003;77:416-424 (Pubitemid 36831205)
100. Bakker J, Honda S, Harada N, Balthazart J. Restoration of male sexual behavior by adult exogenous estrogens in male aromatase knockout mice. Horm Behav 2004;46:1-10 (Pubitemid 38822931)
101. Alsum P, Goy RW. Actions of esters of testosterone, dihydrotestosterone, or estradiol on sexual behavior in castrated male guinea pigs. Horm Behav 1974;5:207-217
102. Phoenix CH. Effect of dihydrotestosterone on sexual behavior of castrated male rhesus monkeys. Physiol Behav 1974;12:1045-1055
103. Zumpe D, Clancy AN, Bonsall RB, Michael RP. Behavioral responses to depo-provera, fadrozole, and estradiol in castrated, testosterone-treated cynomolgus monkeys (Macaca fascicularis): the involvement of progestin receptors. Physiol Behav 1996;60:531-540 (Pubitemid 26274295)
104. Gooren LJ. Human male sexual functions do not require aromatization of testosterone: a study using tamoxifen, testolactone, and dihydrotestosterone. Arch Sex Behav 1985;14:539-548 (Pubitemid 16210916)
105. Sharma TP, Blache D, Blackberry MA, Martin GB. Role of peripheral and central aromatization in the control of gonadotrophin secretion in the male sheep. Reprod Fertil Dev 1999;11:293-302 (Pubitemid 30262661)
106. Hayes FJ, Seminara SB, Decruz S, Boepple PA, CrowleyWF Jr. Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback. [In Process Citation]J Clin Endocrinol Metab 2000;85:3027-3035 (Pubitemid 30944499)
107. Couse JF, Korach KS. Estrogen receptor null mice: what have we learned and where will they lead us? Endocr Rev 1999;20:358-417
108. Jones MEE, Chin BW, Proietto J, Simpson ER. Of mice and men: the evolving phenotype of aromatase deficiency. Trends Endocrinol Metab 2006;17:55-64 (Pubitemid 43306728)
109. Ellinwood WE, Hess DL, Roselli CE, Spies HG, Resko JA. Inhibition of aromatization stimulates luteinizing hormone and testosterone secretion in adult male rhesus monkeys. J Clin Endocrinol Metab 1984;59:1088-1096 (Pubitemid 15223342)
110. Roselli CE, Stadelman H, Horton LE, Resko JA. Regulation of androgen metabolism and luteinizing hormone- releasing hormone content in discrete hypothalamic and limbic areas of male rhesus macaques. Endocrinology 1987;120:97-106 (Pubitemid 17232662)
111. Schnorr JA, Bray MJ, Veldhuis JD. Aromatization mediates testosterone's short-term feedback restraint of 24-hour endogenously driven and acute exogenous gonadotropinreleasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone secretion in young men. J Clin Endocrinol Metab 2001;86:2600-2606 (Pubitemid 32545712)
112. Bagatell CJ, Dahl KD, Bremner WJ. The direct pituitary effect of testosterone to inhibit gonadotropin secretion in men is partially mediated by aromatization to estradiol. J Androl 1994;15:15-21 (Pubitemid 24061781)
113. Boyar RM, Moore RJ, Rosner W, et al. Studies of gonadotropin-gonadal dynamics in patients with androgen insensitivity. J Clin Endocrinol Metab 1978;47:1116-1122 (Pubitemid 9047402)
114. Veldhuis JD, Urban RJ, Dufau ML. Evidence that androgen negative feedback regulates hypothalamic gonadotropinreleasing hormone impulse strength and the burst-like secretion of biologically active luteinizing hormone in men. J Clin Endocrinol Metab 1992;74:1227-1235
115. Pitteloud N, Dwyer AA, Decruz S, et al. Inhibition of luteinizing hormone secretion by testosterone in men requires aromatization for its pituitary but not its hypothalamic effects: evidence from the tandem study of normal and gonadotropin-releasing hormone-deficient men. J Clin Endocrinol Metab 2008;93:784-791
116. Hall ED, Pazara KE, Linseman KL. Sex differences in postischemic neuronal necrosis in gerbils. J Cereb Blood Flow Metab 1991;11:292-298
117. Alkayed NJ, Harukuni I, Kimes AS, London ED, Traystman RJ, Hurn PD. Gender-linked brain injury in experimental stroke. Stroke 1998;29:159-166 (Pubitemid 28046959)
118. Alkayed NJ, Murphy SJ, Traystman RJ, Hurn PD. Neuroprotective effects of female gonadal steroids in reproductively senescent female rats. Stroke 2000;31:161-168 (Pubitemid 30035770)
119. Carswell HV, Anderson NH, Clark JS, et al. Genetic and gender influences on sensitivity to focal cerebral ischemia in the stroke-prone spontaneously hypertensive rat. Hypertension 1999;33:681-685 (Pubitemid 29091647)
120. McCullough LD, Blizzard K, Simpson ER, Oz OK, Hurn PD. Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection. J Neurosci 2003;23: 8701-8705 (Pubitemid 37176650)
121. Li X, Blizzard KK, Zeng Z, DeVries AC, Hurn PD, McCullough LD. Chronic behavioral testing after focal ischemia in the mouse: functional recovery and the effects of gender. Exp Neurol 2004;187:94-104 (Pubitemid 38470016)
122. Bramlett HM, Dietrich WD. Neuropathological protection after traumatic brain injury in intact female rats versus males or ovariectomized females. J Neurotrauma 2001;18: 891-900 (Pubitemid 32852890)
123. Hurn PD, Macrae IM. Estrogen as a neuroprotectant in stroke. J Cereb Blood Flow Metab 2000;20:631-652 (Pubitemid 30217502)
124. Morrison JH, Brinton RD, Schmidt PJ, Gore AC. Estrogen, menopause, and the aging brain: how basic neuroscience can inform hormone therapy in women. J Neurosci 2006;26:10332-10348 (Pubitemid 44564581)
125. Bryant DN, Sheldahl LC, Marriott LK, Shapiro RA, Dorsa DM. Multiple pathways transmit neuroprotective effects of gonadal steroids. Endocrine 2006;29:199-207 (Pubitemid 44097363)
126. Vagnerova K, Koerner IP, Hurn PD. Gender and the injured brain. Anesth Analg 2008;107:201-214
127. Azcoitia I, Sierra A, Veiga S, Honda S, Harada N, Garcia-Segura LM. Brain aromatase is neuroprotective. J Neurobiol 2001;47:318-329 (Pubitemid 32467339)
128. Garcia-Segura LM, Azcoitia I, DonCarlos LL. Neuroprotection by estradiol. Prog Neurobiol 2001;63:29-60 (Pubitemid 30748507)
129. Veiga S, Azcoitia I, Garcia-Segura LM. Extragonadal synthesis of estradiol is protective against kainic acid excitotoxic damage to the hippocampus. Neuroreport 2005; 16:1599-1603 (Pubitemid 41783131)
130. Garcia-Ovejero D, Veiga S, Garcia-Segura LM, DonCarlos LL. Glial expression of estrogen and androgen receptors after rat brain injury. J Comp Neurol 2002;450:256-271 (Pubitemid 34809996)
131. Jones MEE, Thornburn AW, Britt KL, et al. Aromatasedeficient (ArKO) mice have a phenotype of increased adiposity. Proc Natl Acad Sci U S A 2000;97:12735-12740 (Pubitemid 30840485)
132. Simpson ER, Clyne C, Rubin G, et al. Aromatase - a brief overview. Annu Rev Physiol 2002;64:93-127
133. Oz OK, Zerwekh JE, Fisher C, et al. Bone has a sexually dimorphic response to aromatase deficiency. J Bone Miner Res 2000;15:507-514 (Pubitemid 30134095)
134. Liu M, Hurn PD, Roselli CE, Alkayed NJ. Role of P450 aromatase in sex-specific astrocytic cell death. J Cereb Blood Flow Metab 2007;27:135-141 (Pubitemid 46006591)
135. Liu M, Oyarzabal EA, Yang R, Murphy SJ, Hurn PD. A novel method for assessing sex-specific and genotypespecific response to injury in astrocyte culture. J Neurosci Methods 2008;171:214-217
136. Toung TK, Hurn PD, Traystman RJ, Sieber FE, Faraci FM. Estrogen decreases infarct size after temporary focal ischemia in a genetic model of type 1 diabetes mellitus: editorial comment. Stroke 2000;31:2701-2706 (Pubitemid 30813066)
137. Vannucci SJ, Willing LB, Goto S, et al. Experimental stroke in the female diabetic, db/db, mouse. J Cereb Blood Flow Metab 2001;21:52-60 (Pubitemid 32016839)
138. Alkayed NJ, Murphy SJ, Traystman RJ, Hurn PD, Miller VM. Neuroprotective effects of female gonadal steroids in reproductively senescent female rats. Stroke 2000;31:161-168 (Pubitemid 30035770)