Estradiol synthesis and action at the synapse: Evidence for "synaptocrine" signaling

Frontiers in Endocrinology

Volumn 2, Issue SEP, 2011, Pages

  Remage Healey, Luke ^a   Saldanha, Colin J ^b   Schlinger, Barney A ^a,c  

^a UNIVERSITY OF MASSACHUSETTS   (United States)

^b AMERICAN UNIVERSITY   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Aromatase; Neurosteroid; Sex steroid; Songbird; Steroidogenesis

Indexed keywords

EID: 84858161724     PISSN: None     EISSN: 16642392     Source Type: Journal    
DOI: 10.3389/fendo.2011.00028     Document Type: Review

References (151)

1. Adkins, E. K., and Adler, N. T. (1972). Hormonal control of behavior in the Japanese quail. J. Comp. Physiol. Psychol. 81, 27-36.
2. Adkins Regan, E. (1981). Effect of sex steroids on the reproductive-behavior of castrated male Ring Doves (Streptopelia-Sp). Physiol. Behav. 26, 561-565.
3. Adkins-Regan, E., Abdelnabi, M., Mobarak, M., and Ottinger, M. A. (1990). Sex steroid levels in developing and adult male and female zebra finches (Poephila guttata). Gen. Comp. Endocrinol. 78, 93-109.
4. Arnold, A. P., and Schlinger, B. A. (1993). Sexual-differentiation of brain and behavior - the zebra finch is not just a flying rat. Brain Behav. Evol. 42, 231-241.
5. Ball, G. F., and Balthazart, J. (2002). "Neuroendocrine mechanisms regulating reproductive cycles and reproductive behavior in birds," in Hormones, Bran and Behavior, ed. D. W. Pfaff (Amsterdam: Academic Press), 649-798.
6. Balthazart, J., Foidart, A., Surlemont, C., Vockel, A., and Harada, N. (1990). Distribution of aromatase in the brain of the Japanese quail, ring dove, and zebra finch: an immuno-cytochemical study. J. Comp. Neurol. 301, 276-288.
7. Balthazart, J. (1990). Brain aromatiza-tion of testosterone regulates male reproductive behavior in birds. Prog. Clin. Biol. Res. 342, 92-98.
8. Balthazart, J., Absil, P., Foidart, A., Houbart, M., Harada, N., and Ball, G. F. (1996). Distribution of aromatase-immunoreactive cells in the forebrain of zebra finches (Taeniopygia guttata): implications for the neural action of steroids and nuclear definition in the avian hypothalamus. J. Neurobiol. 31, 129-148.
9. Balthazart, J., Baillien, M., and Ball, G. (2001). Rapid and reversible inhibition of brain aromatase activity. J. Neuroendocrinol. 13, 63-73.
10. Balthazart, J., Baillien, M., and Ball, G. F. (2006). Rapid control of brain aromatase activity by glutamatergic inputs. Endocrinology 147, 359-366.
11. Balthazart, J., Baillien, M., Char-lier, T., and Ball, G. (2003). Calcium-dependent phosphoryla-tion processes control brain aro-matase in quail. Eur. J. Neurosci. 17, 1591-1606.
12. Balthazart, J., Baillien, M., Charlier, T., and Ball, G. (2005). Effects of calmodulin on aromatase activity in the preoptic area. J. Neuroendocrinol. 17, 664-671.
13. Balthazart, J., Baillien, M., Cornil, C. A., and Ball, G. F. (2004). Preoptic aromatase modulates male sexual behavior: slow and fast mechanisms of action. Physiol. Behav. 83, 247-270.
14. Balthazart, J., and Ball, G. F. (2006). Is brain estradiol a hormone or a neu-rotransmitter? Trends Neurosci. 29, 241-249.
15. Baulieu,E. E., and Robel,P. (1990). Neu-rosteroids - a new brain-function. J. Steroid Biochem. Mol. Biol. 37, 395-403.
16. Beyer, C., Pawlak, J., and Karol-czak, M. (2003). Membrane receptors for oestrogen in the brain. J. Neurochem. 87, 545-550.
17. Blaustein, J. D. (1992). Cytoplas-mic estrogen receptors in rat brain: immunocytochemical evidence using three antibodies with distinct epitopes. Endocrinology 131, 1336-1342.
18. Blaustein, J. D., Lehman, M. N., Tur-cotte, J. C., and Greene, G. (1992). Estrogen-receptors in dendrites and axon terminals in the guinea-pig hypothalamus. Endocrinology 131, 281-290.
19. Bolhuis, J. J., and Gahr, M. (2006). Neural mechanisms of birdsong memory. Nat. Rev. Neurosci. 7, 347-357.
20. Bottjer, S. W., and Johnson, F. (1997). Circuits, hormones, and learning: vocal behavior in songbirds. J. Neu-robiol. 33, 602-618.
21. Caldwell, J. D., Suleman, F., Chou, S. H., Shapiro, R. A., Herbert, Z., and Jirikowski, G. F. (2006). Emerging roles of steroid-binding globulins. Horm. Metab. Res. 38, 206-218.
22. Callard, G. V. (1984). "Aromatization in brain and pituitary: an evolutionary perspective," in Metabolism of Hormonal Steroids in the Neuroendocrine Structures, eds F. Celotti, F. Naftolin, L. Martini (New York: Raven Press), 79-102.
23. Callard, G. V., Petro, Z., and Ryan, K. J. (1978). Phylogenetic distribution of aromatase and other androgen-converting enzymes in the central nervous system. Endocrinology 103, 2283-2290.
24. Canick, J. A., Vaccaro, D. E., Livingston, E. M., Leeman, S. E., Ryan, K. J., and Fox, T. O. (1986). Localization of aromatase and 5α-eductase to neu-ronal and non-neuronal cells in the fetal rat hypothalamus. Brain Res. 372, 277-282.
25. Caria, M. A., Dratman, M. B., Kow, L. M., Mameli, O., and Pavlides, C. (2009). Thyroid hormone action: nongenomic modulation of neu-ronal excitability in the hippocampus. J. Neuroendocrinol. 21, 98-107.
26. Carlisle, H. J., Hales, T. G., and Schlinger, B. A. (1998). Characterization of neuronal zebra finch GABA(A) receptors: steroid effects. J. Comp. Physiol. 182, 531-538.
27. Clayton, N. (2002). Brain, perception, memory: advances in cognitive neu-roscience. Q. J. Exp. Psychol. B 55, 191-192.
28. Compagnone, N. A., Bulfone, A., Rubenstein, J. L., and Mellon, S. H. (1995a). Expression of the steroido-genic enzyme P450scc in the central and peripheral nervous systems during rodent embryogenesis. Endocrinology 136, 2689-2696.
29. Compagnone, N. A., Bulfone, A., Rubenstein, J. L., and Mellon, S. H. (1995b). Steroidogenic enzyme P450c17 is expressed in the embryonic central nervous system. Endocrinology 136, 5212-5223.
30. Cornil, C. A. (2009). Rapid regulation of brain oestrogen synthesis: the behavioural roles of oestrogens and their fates. J. Neuroendocrinol. 21, 217-226.
31. Davis,P. J., Leonard,J. L., and Davis,F. B. (2008). Mechanisms of nongenomic actions of thyroid hormone. Front. Neuroendocrinol. 29, 211-218.
32. Do Rego, J. L., Seong, J. Y., Burel, D., Leprince, J., Luu-The, V., Tsut-sui, K., Tonon, M. C., Pelletier, G., and Vaudry, H. (2009). Neuros-teroid biosynthesis: enzymatic pathways and neuroendocrine regulation by neurotransmitters and neu-ropeptides. Front. Neuroendocrinol. 30, 259-301.
33. Dratman, M. B., and Gordon, J. T. (1996). Thyroid hormones as neu-rotransmitters. Thyroid 6, 639-647.
34. Foidart, A., Harada, N., and Balthaz-art, J. (1994). Effects of steroidal and non steroidal aromatase inhibitors on sexual behavior and aromatase immunoreactive cells and fibers in the quail brain. Brain Res. 657, 105-123.
35. Forlano, P. M., Deitcher, D. L., Myers, D. A., and Bass,A. H. (2001). Anatomical distribution and cellular basis for high levels of aromatase activity in the brain of teleost fish: aromatase enzyme and mRNA expression identify glia as source. J. Neurosci. 21, 8943-8955.
36. Forlano, P. M., Schlinger, B. A., and Bass, A. H. (2006). Brain aro-matase: new lessons from non-mammalian model systems. Front. Neuroendocrinol. 27, 247-274.
37. Fusani, L., Hutchison, J. B., and Gahr, M. (2001). Testosterone regulates the activity and expression of aro-matase in the canary neostriatum. J. Neurobiol. 49, 1-8.
38. Fusani, L., Van't Hof, T., and Hutchison, J. B. (2003). Season-related changes in circulating androgen, brain aro-matase, and perch-calling in male ring doves. Gen. Comp. Endocrinol. 130, 142-147.
39. Grisham, W., Lee, J., Park, S. H., Mankowski, J. L., and Arnold, A. P. (2008). A dose-response study of estradiol's effects on the developing zebra finch song system. Neurosci. Lett. 445, 158-161.
40. Gurney, M., and Konishi, M. (1980). Hormone-induced sexual differentiation of brain and behavior in zebra finches. Science 208, 1380-1383.
41. Hart, S. A., Snyder, M. A., Smejkalova, T., and Woolley, C. S. (2007). Estrogen mobilizes a subset of estrogen receptor-alpha-immunoreactive vesicles in inhibitory presynaptic boutons in hippocampal CA1. J. Neurosci. 27, 2102-2111.
42. Hojo, Y., Hattori, T. A., Enami, T., Furukawa, A., Suzuki, K., Ishii, H. T., Mukai, H., Morrison, J. H., Janssen, W. G., Kominami, S., Harada, N., Kimoto, T., and Kawato, S. (2004). Adult male rat hippocampus synthesizes estradiol from pregnenolone by cytochromes P45017alpha and P450 aromatase localized in neurons. Proc. Natl. Acad. Sci. U.S.A. 101, 865-870.
43. Hojo, Y., Murakami, G., Mukai, H., Higo, S., Hatanake, Y., Ogiue-Ikeda, M., Ishii, H., Kimotot, T., and Kawato, S. (2008). Estrogen synthesis in the brain-role in synaptic plasticity and memory. Mol. Cell. Endocrinol. 290, 31-43.
44. Horvath, T. L., Roa-Pena, L., Jakab, R. L., Simpson, E. R., and Naftolin, F. (1997). Aromatase in axonal processes of early postnatal hypo-thalamic and limbic areas including the cingulate cortex. J. Steroid Biochem. Mol. Biol. 61, 349-357.
45. Hutchison, J. B., and Steimer, T. (1981). Brain 5?-reductase - a correlate of behavioral sensitivity to androgen. Science 213, 244-246.
46. Hutchison, J. B., Wingfield, J. C., and Hutchison, R. E. (1984). Sex differences in plasma concentrations of steroids during the sensitive period for brain differentiation in the zebra finch. J. Endocrinol. 103, 363-369.
47. Immelman, K. (1969). "Song development in the zebra finch and other estrildid finches," in Bird Vocalizations, ed. R. Hinde (Cambridge: Cambridge University Press), 61-74.
48. Jantti, S. E., Tammimaki, A., Raattamaa, H., Piepponen, P., Kostiainen, R., and Ketola, R. A. (2010). Determination of steroids and their intact glu-curonide conjugates in mouse brain by capillary liquid chromatography-tandem mass spectrometry. Anal. Chem. 82, 3168-3175.
49. Katz, P. S. (ed.). (1999). Beyond Neu-rotransmission. New York: Oxford University Press.
50. King,S. R., Manna,P.R., Ishii, T., Syapin, P. J., Ginsberg, S. D., Wilson, K., Walsh, L. P., Parker, K. L., Stocco, D. M., Smith, R. G., and Lamb, D. J. (2002). An essential component in steroid synthesis, the steroidogenic acute regulatory protein,is expressed in discrete regions of the brain. J. Neurosci. 22, 10613-10620.
51. Konishi, M., Emlen, S. T., Ricklefs, R. E., and Wingfield, J. C. (1989). Contributions of bird studies to biology. Science 246, 465-472.
52. Kretz, O., Fester, L., Wehrenberg, U., Zhou, L., Brauckmann, S., Zhao, S., Prange-Kiel, J., Naumann, T., Jarry, H., Frotscher, M., and Rune, G. M. (2004). Hippocampal synapses depend on hippocampal estrogen synthesis. J. Neurosci. 24, 5913-5921.
53. Lan, N. C., and Gee, K. W. (1994). Neuroactive steroid actions at the GABAA receptor. Horm. Behav. 28, 537-544.
54. Lephart, E. D. (1996). A review of brain aromatase cytochrome P450. Brain Res. Rev. 22, 1-26.
55. Loewi, O. (1921). Uber humorale Uber-tragbarkeit der Herznervenwirkung. Pflugers Arch. 189:239-242.
56. London, S., Monks, D. A., Wade, J., and Schlinger, B. A. (2006). Widespread capacity for steroid synthesis in the avian brain and song system. Endocrinology 147, 5975-5987.
57. London, S., and Schlinger, B. A. (2007). Steroidogenic enzymes along the ventricular proliferative zone in the developing songbird brain. J. Comp. Neurol. 502, 507-521.
58. London, S. E., Boulter, J., and Schlinger, B. A. (2003). Cloning of the zebra finch androgen synthetic enzyme CYP17: a study of its neural expression throughout posthatch development. J. Comp. Neurol. 467, 496-508.
59. London, S. E., Itoh,Y., Lance,V. A.,Wise, P. M., Ekanayake, P. S., Oyama, R. K., Arnold, A. P., and Schlinger, B. A. (2010). Neural expression and post-transcriptional dosage compensation of the steroid metabolic enzyme 17beta-HSD type 4. BMC Neurosci. 11, 47. doi: 10.1186/1471-2202-11-47
60. London, S. E., Remage-Healey, L., and Schlinger, B. A. (2009). Neurosteroid production in the songbird brain: a re-evaluation of core principles. Front. Neuroendocrinol. 30, 302-314.
61. Maclusky, N. J., and Naftolin, F. (1981). Sexual differentiation of the central nervous system. Science 211, 1294-1302.
62. Majewska, M. D. (1992). Neurosteroids: endogenous bimodal modulators of the GABAA receptor. Mechanism of action and physiological significance. Prog. Neurobiol. 38, 379-395.
63. Majewska, M. D., Harrison, N. L., Schwartz, R. D., Barker, J. L., and Paul, S. M. (1986). Steroid-hormone metabolites are barbiturate-like modulators of the gaba receptor. Science 232, 1004-1007.
64. Martini, L. (1982). The 5alpha-reduction of testosterone in the neuroendocrine structures. Biochemical and biophysical implications. Endocr. Rev. 3, 1-25.
65. Mcewen, B. S. (1981). Neural gonadal steroid actions. Science 211, 1303-1311.
66. Mcewen, B. S., and Alves, S. E. (1999). Estrogen actions in the central nervous system. Endocr. Rev. 20, 279-307.
67. Mcleod, J. F., and Cooke, N. E. (1989). The vitamin D-binding protein, alpha-fetoprotein, albumin multi-gene family: detection of transcripts in multiple tissues. J. Biol. Chem. 264, 21760-21769.
68. Meitzen, J., and Mermelstein, P. G. (2011). Estrogen receptors stimulate brain region specific metabotropic glutamate receptors to rapidly initiate signal transduction pathways. J. Chem. Neuroanat. PMID: 21458561. [Epub ahead of print].
69. Meitzen, J., Moore, I. T., Lent, K., Brenowitz, E. A., and Perkel, D. J. (2007). Steroid hormones act transsynaptically within the fore-brain to regulate neuronal pheno-type and song stereotypy. J. Neurosci. 27, 12045-12057.
70. Mermelstein, P. G., Becker, J. B., and Surmeier, D. J. (1996). Estradiol reduces calcium currents in rat neos-triatal neurons via a membrane receptor. J. Neurosci. 16, 595-604.
71. Micevych, P. E., and Mermelstein, P. G. (2008). Membrane estrogen receptors acting through metabotropic glutamate receptors: an emerging mechanism of estrogen action in brain. Mol. Neurobiol. 38, 66-77.
72. Miller, W. L. (1988). Molecular biology of steroid hormone synthesis. Endocr. Rev. 9, 295-318.
73. Milner, T. A., Mcewen, B. S., Hayashi, S., Li, C. J., Reagan, L. P., and Alves, S. E. (2001). Ultrastructural evidence that hippocampal alpha estrogen receptors are located at extranu-clear sites. J. Comp. Neurol. 429, 355-371.
74. Mitterling, K. L., Spencer, J. L., Dziedzic, N., Shenoy, S., Mccarthy, K., Waters, E. M., Mcewen, B. S., and Milner, T. A. (2010). Cellular and subcellular localization of estrogen and prog-estin receptor immunoreactivities in the mouse hippocampus. J. Comp. Neurol. 518, 2729-2743.
75. Moenter, S. M., and Chu, Z. (2011). Rapid non-genomic effects of oestradiol on GnRH neurons. J. Neuroendocrinol. doi: 10.1111/j.1365-2826.2011.02135.x. [Epub ahead of print].
76. Montague, D., Weickert, C. S., Tomaskovic-Crook, E., Roth-mond, D. A., Kleinman, J. E., and Rubinow, D. R. (2008). Oestrogen receptor alpha localisation in the prefrontal cortex of three mammalian species. J. Neuroendocrinol. 20, 893-903.
77. Mooney, R. (2009). Neurobiology of song learning. Curr. Opin. Neurobiol. 19, 654-660.
78. Mukai, H., Takata, N., Ishii, H. T., Tanabe, N., Hojo, Y., Furukawa, A., Kimoto, T., and Kawato, S. (2006). Hippocampal synthesis of estrogens and androgens which are paracrine modulators of synaptic plasticity: synaptocrinology. Neuroscience 138, 757-764.
79. Murakami, G., Tanabe, N., Ishii, H. T., Ogiue-Ikeda, M., Tsu-rugizawa, T., Mukai, H., Hojo, Y., Takata, N., Furukawa, A., Kimoto, T., and Kawato, S. (2006). Role of cytochrome P450 in synaptocrinology: endogenous estrogen synthesis in the brain hippocampus. Drug Metab. Rev. 38, 353-369.
80. Naftolin, F., Horvath, T. L., Jakab, R. L., Leranth, C., Harada,N., and Balthaz-art, J. (1996). Aromatase immunore-activity in axon terminals of the vertebrate brain. An immunocyto-chemical study on quail, rat, monkey and human tissues. Neuroen-docrinology 63, 149-155.
81. Naftolin, F., Ryan, K. J., Davies, I. J., Reddy, V. V., Flores, F., Petro, Z., Kuhn, M., White, R. J., Takaoka, Y., and Wolin, L. (1975). The formation of estrogens by central neuroen-docrine tissues. Rec. Prog. Horm. Res. 31, 295-319.
82. Naftolin, F., Ryan, K. J., and Petro, Z. (1971). Aromatization of androstenedione by limbic system tissue from human foetuses. J. Endocrinol. 51, 795-796.
83. Nottebohm, F., and Arnold, A. P. (1976). Sexual dimorphism in vocal control areas of the songbird brain. Science 194, 211-213.
84. Nottebohm, F., Stokes, T. M., and Leonard, C. M. (1976). Central control of song in the canary, Seri-nus canarius. J. Comp. Neurol. 165, 457-486.
85. Oberlander, J. G., Schlinger, B. A., Clayton, N. S., and Saldanha, C. J. (2004). Neural aromatization accelerates the acquisition of spatial memory via an influence on the songbird hippocampus. Horm. Behav. 45, 250-258.
86. Pasmanik, M., Schlinger, B. A., and Callard, G. V. (1988). In vivo steroid regulation of aromatase and 5α-reductase in goldfish brain and pituitary. Gen. Comp. Endocrinol. 71, 175-182.
87. Payne, A. H., and Hales, D. B. (2004). Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr. Rev. 25, 947-970.
88. Peterson, R. S., Yarram, L., Schlinger, B. A., and Saldanha, C. J. (2005). Aro-matase is pre-synaptic and sexually dimorphic in the adult zebra finch brain. Proc. R. Soc. B Biol. Sci. 272, 2089-2096.
89. Portillo, W., Castillo, C. G., Retana-Marquez, S., Roselli, C. E., and Pare-des, R. G. (2007). Neuronal activity of aromatase enzyme in non-copulating male rats. J. Neuroen-docrinol. 19, 139-141.
90. Pradhan, D. S., Newman, A. E., Wacker, D. W., Wingfield, J. C., Schlinger, B. A., and Soma, K. K. (2010). Aggressive interactions rapidly increase androgen synthesis in the brain during the non-breeding season. Horm. Behav. 57, 381-389.
91. Prange-Kiel, J., and Rune, G. M. (2006). Direct and indirect effects of estrogen on rat hippocampus. Neuro-science 138, 765-772.
92. Reddy, D. S. (2010). Neurosteroids: endogenous role in the human brain and therapeutic potentials. Prog. Brain Res. 186, 113-137.
93. Remage-Healey, L., and Bass, A. H. (2006). A rapid neuromodulatory role for steroid hormones in the control of reproductive behavior. Brain Res. 1126, 27-35.
94. Remage-Healey, L., Coleman, M. J., Oyama, R. K., and Schlinger, B. A. (2010a). Brain estrogens rapidly strengthen auditory encoding and guide song preference in a songbird. Proc. Natl. Acad. Sci. U.S.A.107, 3852-3857.
95. Remage-Healey, L., London, S. E., and Schlinger, B. A. (2010b). Bird-song and the neural production of steroids. J. Chem. Neuroanat. 39, 72-81.
96. Remage-Healey, L., Dong, S., Maid-ment, N. T., and Schlinger, B. A. (2011). Presynaptic control of rapid estrogen fluctuations in the songbird auditory forebrain. J. Neurosci. 31, 10034-10038.
97. Remage-Healey, L., Maidment, N. T., and Schlinger, B. A. (2008). Fore-brain steroid levels fluctuate rapidly during social interactions. Nat. Neu-rosci. 11, 1327-1334.
98. Remage-Healey, L., Oyama, R. K., and Schlinger, B. A. (2009). Elevated aro-matase activity in forebrain synaptic terminals during song. J. Neuroen-docrinol. 21, 191-199.
99. Riters, L., Baillien, M., Eens, M., Pinxten, R., Foidart, A., Ball, G., and Balthaz-art, J. (2001). Seasonal variation in androgen-metabolizing enzymes in the diencephalon and telencephalon of the male European starling (Stur-nus vulgaris). J. Neuroendocrinol. 13, 985-997.
100. Roepke, T. A., Ronnekleiv, O. K., and Kelly, M. J. (2011). Physiological consequences of membrane-initiated estrogen signaling in the brain. Front. Biosci. 16, 1560-1573.
101. Rohmann, K. N., Schlinger, B. A., and Saldanha, C. J. (2007). Subcellular compartmentalization of aromatase is sexually dimorphic in the adult zebra finch brain. Dev. Neurobiol. 67, 1-9.
102. Roselli, C. E. (1991). Synergistic induction of aromatase-activity in the rat-brain by estradiol and 5α-dihydrotestosterone. Neuroendocrinology 53, 79-84.
103. Roselli, C. E., Cross, E., Poonya-gariyagorn, H. K., and Stadelman, H. L. (2003). Role of aromatization in anticipatory and consummatory aspects of sexual behavior in male rats. Horm. Behav. 44, 146-151.
104. Roselli, C. E., and Resko, J. A. (2001). Cytochrome P450 aromatase (CYP19) in the non-human primate brain: distribution, regulation, and functional significance. J. Steroid Biochem. Mol. Biol. 79, 247-253.
105. Rozanov, C. B., and Dratman, M. B. (1996). Immunohistochemical mapping of brain triiodothyronine reveals prominent localization in central noradrenergic systems. Neu-roscience 74, 897-915.
106. Saldanha, C. J., and Coomaralingam, L. (2005). Overlap and co-expression of estrogen synthetic and responsive neurons in the songbird brain - a double-label immunocytochem-ical study. Gen. Comp. Endocrinol. 141, 66-75.
107. Saldanha, C. J., Duncan, K. A., and Walters, B. J. (2009). Neuroprotective actions of brain aromatase. Front. Neuroendocrinol. 30, 106-118.
108. Saldanha, C. J., Peterson, R. S., Yarram, L., and Schlinger, B. A. (2003). The synaptocrine hypothesis: a novel form of estrogen delivery. Abstr. Soc. Neurosci. Abstract 610.14.
109. Saldanha, C. J., Popper, P., Micevych, P. E., and Schlinger, B. A. (1998). The passerine hippocampus is a site of high aromatase: inter- and intraspecies comparisons. Horm. Behav. 34, 85-97.
110. Saldanha, C. J., Remage-Healey, L., and Schlinger, B. A. (2011). Synap-tocrine signaling: steroid synthesis and action at the synapse. Endocr. Rev. 32, 532-549.
111. Saldanha, C. J., and Schlinger, B. A. (1997). Estrogen synthesis and secretion in the brown-headed cow-bird (Molothrus ater). Gen. Comp. Endocrinol. 105, 390-401.
112. Saldanha, C. J., and Schlinger, B. A. (2008). "Steroidogenesis and neuroplasticity in the songbird brain," in Neuroactive Steroids in Brain Function, Behavioral and Neuropsychiatric Disorders. Novel Strategies for Research and Treatment, eds M. S. Ritsner and A. Weizman (Pondicherry: Springer), 201-218.
113. Saldanha, C. J., Schlinger, B. A., Micevych, P. E., and Horvath, T. L. (2004). Presynaptic N-methyl-D-aspartate receptor expression is increased by estrogen in an aromatase-rich area of the songbird hippocampus. J. Comp. Neurol. 469, 522-534.
114. Saldanha, C. J., Tuerk, M. J., Kim, Y. H., Fernandes, A. O., Arnold, A. P., and Schlinger, B. A. (2000). Distribution and regulation of telen-cephalic aromatase expression in the zebra finch revealed with a specific antibody. J. Comp. Neurol. 423, 619-630.
115. Santen, R. J., Brodie, H., Simpson, E. R., Siiteri, P. K., and Brodie, A. (2009). History of aromatase: saga of an important biological mediator and therapeutic target. Endocr. Rev. 30, 343-375.
116. Scharrer, E. (1954). Neurosecretion and anterior pituitary in the dog. Experi-entia 10, 264-266.
117. Schlinger, B. A., Amur-Umarjee, S., Campagnoni, A. T., and Arnold, A. P. (1995). 5β-reductase and other androgen-metabolizing enzymes in primary cultures of developing zebra finch telencephalon. J. Neuroen-docrinol. 7, 187-192.
118. Schlinger, B. A., and Arnold, A. P. (1991). Brain is the major site of estrogen synthesis in a male songbird. Proc. Natl. Acad. Sci. U.S.A. 88, 4191-4194.
119. Schlinger, B. A., and Arnold, A. P. (1992a). Circulating estrogens in a male songbird originate in the brain. Proc. Natl. Acad. Sci. U.S.A. 89, 7650-7653.
120. Schlinger, B. A., and Arnold, A. P. (1992b). Plasma sex steroids and tissue aromatization in hatchling zebra finches: implications for the sexual differentiation of singing behavior. Endocrinology 130, 289-299.
121. Schlinger, B. A., and Callard, G. V. (1989a). Estrogen receptors in quail brain: a functional relationship to aromatase and aggressiveness. Biol. Reprod. 40, 268-275.
122. Schlinger, B. A., and Callard, G. V. (1989b). Localization of aromatase in synaptosomal and microsomal subfractions of quail (Coturnix coturnix japonica) brain. Neuroen-docrinology 49, 434-441.
123. Schlinger, B. A., Slotow, R. H., and Arnold, A. P. (1992). Plasma estrogens and brain aromatase in winter white-crowned sparrows. Ornis Scand. 23, 292-297.
124. Shen, P., Campagnoni, C. W., Kampf, K., Schlinger, B. A., Arnold, A. P., and Campagnoni, A. T. (1994). Isolation and characterization of a zebra finch aromatase cDNA - in situ hybridization reveals high aromatase expression in brain. Mol. Brain Res. 24, 227-237.
125. Shen, P., Schlinger, B. A., Campagnoni, A. T., and Arnold, A. P. (1995). An atlas of aromatase mRNA expression in the zebra finch brain. J. Comp. Neurol. 360, 172-184.
126. Silverin, B., Baillien, M., Foidart, A., and Balthazart, J. (2000). Distribution of aromatase activity in the brain and peripheral tissues of passerine and nonpasserine avian species. Gen. Comp. Endocrinol. 117, 34-53.
127. Simpson, E. R., Clyne, C., Rubin, G., Boon, W. C., Robertson, K., Britt, K., Speed, C., and Jones, M. (2002). Aro-matase - a brief overview. Annu. Rev. Physiol. 64, 93-127.
128. Simpson, H. B., and Vicario, D. S. (1991). Early estrogen treatment of female zebra finches masculinizes the brain pathway for learned vocalizations. J. Neurobiol. 22, 777-793.
129. Smejkalova, T., and Woolley, C. S. (2010). Estradiol acutely potentiates hippocampal excitatory synap-tic transmission through a presy-naptic mechanism. J. Neurosci. 30, 16137-16148.
130. Snyder, S. H. (2009). Neurotransmit-ters, receptors, and second messengers galore in 40 years. J. Neurosci. 29, 12717-12721.
131. Soma, K. K., Bindra, R.K., Gee, J., Wing-field, J., and Schlinger, B. A. (1999). Androgen metabolizing enzymes show region-specific changes across the breeding season in the brain of a wild breeding song bird. J. Neurobiol. 41, 176-188.
132. Soma, K. K., Schlinger, B. A., Wing-field, J. C., and Saldanha,C. J. (2003). Brain aromatase, 5α-reductase, and 5β-reductase change seasonally in wild male song sparrows: relationship to aggressive and sexual behavior. J. Neurobiol. 56, 209-221.
133. Soma, K. K., and Wingfield, J. C. (2001). Dehydroepiandrosterone in songbird plasma: seasonal regulation and relationship to territorial aggression. Gen. Comp. Endocrinol. 123, 144-155.
134. Soma, K. K.,Wissman,A. M., Brenowitz, E. A., and Wingfield, J. C. (2002). Dehydroepiandrosterone (DHEA) increases territorial song and the size of an associated brain region in a male songbird. Horm. Behav. 41, 203-212.
135. Srivastava, D. P., Woolfrey, K. M., Liu, F., Brandon, N. J., and Penzes, P. (2010). Estrogen receptor ss activity modulates synaptic signaling and structure. J. Neurosci. 30, 13454-13460.
136. Szego, C. M., and Davis, J. S. (1967). Adenosine 3',5'-monophosphate in rat uterus: acute elevation by estrogen. Proc. Natl. Acad. Sci. U.S.A. 58, 1711-1718.
137. Szekely, A. D., and Krebs, J. R. (1996). Efferent connectivity of the hippocampal formation of the zebra finch (Taenopygia guttata): an anterograde pathway tracing study using Phaseolus vulgaris leucoag-glutinin. J. Comp. Neurol. 368, 198-214.
138. Tabori, N. E., Stewart, L. S., Znamen-sky, V., Romeo, R. D., Alves, S. E., Mcewen, B. S., and Milner, T. A. (2005). Ultrastructural evidence that androgen receptors are located at extranuclear sites in the rat hippocampal formation. Neuroscience 130, 151-163.
139. Tam, H., and Schlinger, B. A. (2007). Activities of 3β3-HSD and aromatase in slices of the adult and developing zebra finch brain. Gen. Comp. Endocrinol. 150,26-33.
140. Tramontin, A. D., Wingfield, J. C, and Brenowitz, E. A. (2003). Androgens and estrogens induce seasonal-like growth of song nuclei in the adult songbird brain. J. Neurobiol 57, 130-140.
141. Tremere, L. A., Jeong, J. K., and Pinaud, R. (2009). Estradiol shapes auditory processing in the adult brain by regulating inhibitory transmission and plasticity-associated gene expression. J. Neurosci. 29, 5949-5963.
142. Tremere, L. A., and Pinaud, R. (2011). Brain-generated estradiol drives long-term optimization of auditory coding to enhance the discrimination of communication signals. J. Neurosci. 31, 3271-3289.
143. Tsutsui, K., Haraguchi, S., Matsunaga, M., Koyama, T., Do Rego, J. L., and Vaudry, H. (2010). Identification of 7a-hydroxypregnenolone, a novel bioactive amphibian neuros-teroid stimulating locomotor activity, and its physiological roles in the regulation of locomotion. Gen. Comp. Endocrinol. 168,275-279.
144. Tsutsui, K., Matsunaga, M., Miyabara, H., and Ukena, K. (2004). Identification and mode of action of a novel neurosteroid stimulating locomotor activity. Zool. Sci. 21, 1201-1202.
145. Vanson, A., Arnold, A. P., and Schlinger, B A. (1996). 3β3-hydroxysteroid dehydrogenase/isomerase and aromatase activity in primary cultures of developing zebra finchtelencephalon: dehydroepiandros-terone as substrate for synthesis of androstenedione and estrogens. Gen. Comp. Endocrinol. 102, 342-350.
146. Vockel, A., Pröve, E., and Balthaz-art, J. (1990a). Effects of castration and testosterone treatment on the activity of testosterone-metabolizing enzymes in the brain of male and female zebra finches. J. Neurobiol. 21, 808-825.
147. Vockel, A., Pröve, E., and Balthazart, J. (1990b). Sex- and age-related differences in the activity of testosterone-metabolizing enzymes in microdis-sected nuclei of the zebra finch brain. Brain Res. 511, 291-302.
148. Wade, J., Schlinger, B. A., and Arnold, A. P. (1995). Aromatase and 5α-reductase activity in cultures of developing zebra finch brain: an Investigation of sex and regional differences. J. Neurobiol. 27, 240-251.
149. Waters, E. M., Yildirim, M., Janssen, W. G., Lou, W. Y., Mcewen, B. S., Morrison, J. H., and Milner, T. A. (2011). Estrogen and aging affect the synaptic distribution of estrogen receptorβ-immunoreactivity in the CA1 region of female rat hippocampus. Brain Res. 1379, 86-97.
150. Woolley, C. S. (2007). Acute effects of estrogen on neuronal physiology. Annu. Rev. Pharmacol. Toxicol. 47, 657-680.
151. Wu, M. V., Manoli, D. S., Fraser, E. J., Coats, J. K., Tollkuhn, J., Honda, S., Harada, N., and Shah, N. M. (2009). Estrogen masculinizes neural pathways and sex-specific behaviors. Cell 139, 61-72.