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Semin Reprod Med 2007; 25(3): 165-177
DOI: 10.1055/s-2007-973429
DOI: 10.1055/s-2007-973429
Membrane-Initiated Signaling of Estrogen in the Brain
Weitere Informationen
Publikationsverlauf
Publikationsdatum:
20. April 2007 (online)
ABSTRACT
It is well known that many of the actions of estrogen in the central nervous system are mediated via intracellular receptor/transcription factors that interact with steroid response elements on target genes. However, there now exists compelling evidence for membrane steroid receptors for estrogen in hypothalamic and other brain neurons. It is not well understood how estrogen signals via membrane receptors, and how these signals influence not only membrane excitability but also gene transcription in neurons. Indeed, it has been known for some time that estrogen can rapidly alter neuronal activity within seconds, indicating that some cellular effects can occur via membrane-delimited events. In addition, estrogen can affect second messenger systems including calcium mobilization and a plethora of kinases to alter cell signaling. Therefore, this review considers our current knowledge of rapid membrane-initiated and intracellular signaling by estrogen in the brain, and the nature of receptors involved and how they contribute to homeostatic functions.
KEYWORDS
G protein-coupled receptor - Gαq - K+ channels - pCREB
REFERENCES
- 1 Barraclough C A, Cross B A. Unit activity in the hypothalamus of the cyclic female rat: effect of genital stimuli and progesterone. J Endocrinol. 1963; 26 339-359
- 2 Lincoln D W. Unit activity in the hypothalamus, septum and preoptic area of the rat: Characteristics of spontaneous activity and the effect of oestrogen. J Endocrinol. 1967; 37 177-189
- 3 Lincoln D W, Cross B A. Effect of oestrogen on the responsiveness of neurons in the hypothalamus, septum and preoptic area of rats with light-induced persistent oestrus. J Endocrinol. 1967; 37 191-203
- 4 Moss R L, Law O T. The estrous cycle: its influence on single unit activity in the forebrain. Brain Res. 1971; 30 435-438
- 5 Cross B A, Dyer R G.
Characterization of unit activity in hypothalamic islands with special reference to hormone effects . In: Martini L, Motta M, Fraschini F The Hypothalamus. New York; Academic Press 1970: 115-122MissingFormLabel - 6 Dyer R G, Pritchett C J, Cross B A. Unit activity in the diencephalon of female rats during the oestrus cycle. J Endocrinol. 1972; 53 151-160
- 7 Yagi K, Sawaki Y. Changes in the electrical activity of the hypothalamus during sexual cycle and the effect of castration on it in the female rat. Nippon Seirigaku Zasshi. 1971; 33 546-547
- 8 Bueno J, Pfaff D W. Single unit recordings in the hypothalamus and preoptic area of estrogen-treated and untreated ovariectomized female rats. Brain Res. 1976; 101 67-78
- 9 Yagi K. Effects of estrogen on the unit activity of the rat hypothalamus. Nippon Seirigaku Zasshi. 1970; 32 629-693
- 10 Kubo K, Gorski R A, Kawakami M. Effects of estrogen on neuronal excitability in the hippocampal-septal-hypothalamic system. Neuroendocrinology. 1975; 18 176-191
- 11 Yagi K. Changes in firing rates of single preoptic and hypothalamic units following an intravenous administration of estrogen in the castrated female rat. Brain Res. 1973; 53 343-352
- 12 Whitehead S A, Ruf K B. Responses of antidromically identified preoptic neurons in the rat to neurotransmitters and to estrogen. Brain Res. 1974; 79 185-198
- 13 Dufy B, Partouche C, Poulain D, Dufy-Barbe L, Vincent J D. Effects of estrogen on the electrical activity of identified hypothalamic units. Neuroendocrinology. 1976; 22 38-47
- 14 Jhamandas J H, Renaud L P. Neurophysiology of a Central Baroreceptor Pathway to Hypothalamic Vasopressin Neurons. Can J Neurol Sci. 1987; 14 17-24
- 15 Kelly M J, Moss R L, Dudley C A. Differential sensitivity of preoptic-septal neurons to microelectrophoresed estrogen during the estrous cycle. Brain Res. 1976; 114 152-157
- 16 Kelly M J, Moss R L, Dudley C A. The effects of microelecrophoretically applied estrogen, cortisol, and acetylcholine on medial preoptic-septal unit activity throughout the estrous cycle of the female rat. Exp Brain Res. 1977; 30 53-64
- 17 Kelly M J, Moss R L, Dudley C A, Fawcett C P. The specificity of the response of preoptic-septal area neurons to estrogen: 17α-estradiol versus 17β-estradiol and the response of extrahypothalamic neurons. Exp Brain Res. 1977; 30 43-52
- 18 Kelly M J, Moss R L, Dudley C A.
The stereospecific changes in the unit activity of preoptic-septal neurons to microelectrophoresed estrogen . In: Ryall RW, Kelly JS Iontophoresis and Transmitter Mechanisms in the Mammalian Central Nervous System. New York; Elsevier/North-Holland Biomedical Press 1978: 113-116MissingFormLabel - 19 Kelly M J, Moss R L, Dudley C A. The effects of ovarectomy on preoptic-septic area neurons to microelectrophoresed estrogen. Neuroendocrinology. 1978; 25 204-211
- 20 Kelly M J, Kuhnt U, Wuttke W. Hyperpolarization of hypothalamic parvocellular neurons by 17β-estradiol and their identification through intracellular staining with procion yellow. Exp Brain Res. 1980; 40 440-447
- 21 Nabekura J, Oomura Y, Minami T, Mizuno Y, Fukuda A. Mechanism of the rapid effect of 17β-estradiol on medial amygdala neurons. Science. 1986; 233 226-228
- 22 Minami T, Oomura Y, Nabekura J, Fukuda A. 17β-estradiol depolarization of hypothalamic neurons is mediated by cyclic AMP. Brain Res. 1990; 519 301-307
- 23 Kelly M J, Rønnekleiv O K, Eskay R L. Identification of estrogen-responsive LHRH neurons in the guinea pig hypothalamus. Brain Res Bull. 1984; 12 399-407
- 24 Pietras R J, Szego C M. Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells. Nature. 1977; 265 69-72
- 25 Pietras R J, Szego C M. Estrogen receptors in uterine plasma membrane. J Steroid Biochem. 1979; 11 1471-1483
- 26 Towle A C, Sze P Y. Steroid binding to synaptic plasma membrane: differential binding of glucocorticoids and gonadal steroids. J Steroid Biochem. 1983; 18 135-143
- 27 Zheng J, Ramirez V D. Demonstration of membrane estrogen binding proteins in rat brain by ligand blotting using a 17β-estradiol-[125I]bovine serum albumin conjugate. J Steroid Biochem Mol Biol. 1997; 62 327-336
- 28 Ramirez V D, Zheng J B, Siddique K M. Membrane receptors for estrogen, progesterone, and testosterone in the rat brain: fantasy or reality. Cell Mol Neurobiol. 1996; 16 175-198
- 29 Ramirez V D, Zheng J. Membrane sex-steroid receptors in the brain. Front Neuroendocrinol. 1996; 17 402-439
- 30 Pfaff D, Keiner M. Atlas of estradiol-concentrating cells in the central nervous system of the female rat. J Comp Neurol. 1973; 151 121-158
- 31 Sar M, Stumpf W E.
Cellular localization of progestin and estrogen in guinea pig hypothalamus by autoradiography . In: Stumpf WE, Grant LD Anatomical Neuroendocrinology. Basal, Switzerland; Karger 1975: 142-152MissingFormLabel - 32 Warembourg M. Radioautographic localization of estrogen-concentrating cells in the brain and pituitary of the guinea pig. Brain Res. 1977; 123 357-362
- 33 Sar M. Estradiol is concentrated in tyrosine hydroxylase-containing neurons of the hypothalamus. Science. 1984; 223 938-940
- 34 Tardy J, Pasqualini J R. Localization of [3H]-estradiol and gonadotropin-releasing hormone (GnRH) in the hypothalamus of the fetal guinea-pig. Exp Brain Res. 1983; 49 77-83
- 35 Sar M, Parikh I. Immunohistochemical localization of estrogen receptor in rat brain, pituitary and uterus with monoclonal antibodies. J Steroid Biochem. 1986; 24(2) 497-503
- 36 DonCarlos L L, Monroy E, Morrell J I. Distribution of estrogen receptor-immunoreactive cells in the forebrain of the female guinea pig. J Comp Neurol. 1991; 305 591-612
- 37 Simerly R B, Chang C, Muramatsu M, Swanson L W. Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: an in situ hybridization study. J Comp Neurol. 1990; 294 76-95
- 38 Shughrue P J, Lane M V, Merchenthaler I. Comparative distribution of estrogen receptor-α and -β mRNA in the rat central nervous system. J Comp Neurol. 1997; 388 507-525
- 39 Laflamme N, Nappi R E, Drolet G, Labrie C, Rivest S. Expression and neuropeptidergic characterization of estrogen receptors (ERα and ERβ) throughout the rat brain: Anatomical evidence of distinct roles of each subtype. J Neurobiol. 1998; 36 357-378
- 40 Osterlund M K, Gustafsson J Å, Keller E, Hurd Y L. Estrogen receptor β (ERβ) messenger ribonucleic acid (mRNA) expression within the human forebrain: distinct distribution pattern to ERα mRNA. J Clin Endocrinol Metab. 2000; 85 3840-3846
- 41 Gundlah C, Kohama S G, Mirkes S J, Garyfallou V T, Urbanski H F, Bethea C L. Distribution of estrogen receptor beta (ERbeta) mRNA in hypothalamus, midbrain and temporal lobe of spayed macaque: continued expression with hormone replacement. Brain Res Mol Brain Res. 2000; 76 191-204
- 42 Shughrue P J, Merchenthaler I. Distribution of estrogen receptor beta immunoreactivity in the rat central nervous system. J Comp Neurol. 2001; 436 64-81
- 43 Gréco B, Allegretto E A, Telel M J, Blaustein J D. Coexpression of ERβ and progestin receptor proteins in the female rat forebrain: effects of estradiol treatment. Endocrinology. 2001; 142 5172-5181
- 44 Kruijver F P, Balesar R, Espila A M, Unmehopa U A, Swaab D F. Estrogen receptor-alpha distribution in the human hypothalamus in relation to sex and endocrine status. J Comp Neurol. 2002; 454 115-139
- 45 Kruijver F P, Balesar R, Espila A M, Unmehopa U A, Swaab D F. Estrogen-receptor-beta distribution in the human hypothalamus: similarities and differences with ER alpha distribution. J Comp Neurol. 2003; 466 251-277
- 46 Mitra S W, Hoskin E, Yudkovitz J et al.. Immunolocalization of estrogen receptor beta in the mouse brain: comparison with estrogen receptor alpha. Endocrinology. 2003; 144 2055-2067
- 47 Warembourg M, Leroy D. Comparative distribution of estrogen receptor alpha and beta immunoreactivities in the forebrain and the midbrain of the female guinea pig. Brain Res. 2004; 1002 55-66
- 48 Merchenthaler I, Lane M V, Numan S, Dellovade T L. Distribution of estrogen receptor α and β in the mouse central nervous system in vivo autoradiographic and immunocytochemical analyses. J Comp Neurol. 2004; 473 270-291
- 49 Flügge G, Oertel W H, Wuttke W. Evidence for estrogen-receptive GABAergic neurons in the preoptic/anterior hypothalamic area of the rat brain. Neuroendocrinology. 1986; 43 1-5
- 50 Herbison A E, Theodosis D T. Localization of oestrogen receptors in preoptic neurons containing neurotensin but not tyrosine hydroxylase, cholecystokinin or luteinizing hormone-releasing hormone in the male and female rat. Neuroscience. 1992; 50 283-298
- 51 Herbison A E. Somatostatin-immunoreactive neurones in the hypothalamic ventromedial nucleus possess oestrogen receptors in the male and female rat. J Neuroendocrinol. 1994; 6 323-328
- 52 Horvath T L, Leranth C, Kalra S P, Naftolin F. Galanin neurons exhibit estrogen receptor immunoreactivity in the female rat mediobasal hypothalamus. Brain Res. 1995; 675 321-324
- 53 Skinner D C, Herbison A. Effects of photoperiod on estrogen receptor, tyrosine hydroxylase, neuropeptide Y and β-endorphin immunoreactivity in the ewe hypothalamus. Endocrinology. 1997; 138 2585-2595
- 54 Hrabovszky E, Kallo I, Hajszan T, Shughrue P J, Merchenthaler I, Liposits Z. Expression of estrogen receptor-beta messenger ribonucleic acid in oxytocin and vasopressin neurons of the rat supraoptic and paraventricular nuclei. Endocrinology. 1998; 139 2600-2604
- 55 Cardona-Gomez G P, DonCarlos L, Garcia-Segura L M. Insulin-like growth factor I receptors and estrogen receptors colocalize in female rat brain. Neuroscience. 2000; 99 751-760
- 56 Hrabovszky E, Shughrue P J, Merchenthaler I et al.. Detection of estrogen receptor-β messenger ribonucleic acid and 125I-estrogen binding sites in luteinizing hormone-releasing hormone neurons of the rat brain. Endocrinology. 2000; 141 3506-3509
- 57 Hrabovszky E, Steinhauser A, Barabas K et al.. Estrogen receptor-beta immunoreactivity in luteinizing hormone-releasing hormone neurons of the rat brain. Endocrinology. 2001; 142 3261-3264
- 58 Skynner M J, Sim J A, Herbison A E. Detection of estrogen receptor α and β messenger ribonucleic acids in adult gonadortropin-releasing hormone neurons. Endocrinology. 1999; 140 5195-5201
- 59 Herbison A E, Skynner M J, Sim J A. Lack of detection of estrogen receptor-α transcripts in mouse gonadotropin-releasing hormone neurons. Endocrinology. 2001; 142 492-493
- 60 Goodman R L, Parfitt D B, Evans N P, Dahl G E, Karsch F J. Endogenous opioid peptides control the amplitude and shape of gonadotropin-releasing hormone pulses in the ewe. Endocrinology. 1995; 136 2412-2420
- 61 Bethea C L, Lu N Z, Gundlah C, Streicher J M. Diverse actions of ovarian steroids in the serotonin neural system. Front Neuroendocrinol. 2002; 23 41-100
- 62 Isgor C, Cecchi M, Kabbaj M, Akil H, Watson S J. Estrogen receptor beta in the paraventricular nucleus of hypothalamus regulates the neuroendocrine response to stress and is regulated by corticosterone. Neuroscience. 2003; 121 837-845
- 63 Hrabovszky E, Kallo I, Steinhauser A et al.. Estrogen receptor-beta in oxytocin and vasopressin neurons of the rat and human hypothalamus: immunocytochemical and in situ hybridization studies. J Comp Neurol. 2004; 473 315-333
- 64 Shughrue P J, Scrimo P J, Merchenthaler I. Evidence for the colocalization of estrogen receptor-beta mRNA and estrogen receptor-alpha immunoreactivity in neurons of the rat forebrain. Endocrinology. 1998; 139 5267-5270
- 65 Bao A-M, Hestiantoro A, Van Someren E JW, Swaab D F, Zhou J-N. Colocalization of corticotropin-releasing hormone and oestrogen receptor-α in the paraventricular nucleus of the hypothalamus in mood disorders. Brain. 2005; 128 1301-1313
- 66 McEwen B S, Alves S E. Estrogen actions in the central nervous system. Endocr Rev. 1999; 20 279-307
- 67 Björnström L, Sjöberg M. Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. Mol Endocrinol. 2005; 19 833-842
- 68 Herbison A E. Multimodal influence of estrogen upon gonadotropin-releasing hormone neurons. Endocr Rev. 1998; 19 302-330
- 69 Couse J F, Korach K S. Estrogen receptor null mice: what have we learned and where will they lead us?. Endocr Rev. 1999; 20 358-417
- 70 Nilsson S, Mäkelä S, Treuter E et al.. Mechanisms of estrogen action. Physiol Rev. 2001; 81 1535-1565
- 71 Etgen A M, Ansonoff M A, Quesada A. Mechanisms of ovarian steroid regulation of norepinephrine receptor-mediated signal transduction in the hypothalamus: implications for female reproductive physiology. Horm Behav. 2001; 40 169-177
- 72 O'Malley B W, Tsai M-J. Molecular pathways of steroid receptor action. Biol Reprod. 1992; 46 163-167
- 73 Muramatsu M, Inoue S. Estrogen receptors: how do they control reproductive and nonreproductive functions?. Biochem Biophys Res Commun. 2000; 270 1-10
- 74 Gruber C J, Gruber D M, Gruber I M, Wieser F, Huber J C. Anatomy of the estrogen response element. Trends Endocrinol Metab. 2004; 15 73-78
- 75 Malyala A, Pattee P, Nagalla S R, Kelly M J, Rønnekleiv O K. Suppression subtractive hybridization and microarray identification of estrogen regulated hypothalamic genes. Neurochem Res. 2004; 29 1189-1200
- 76 Paech K, Webb P, Kuiper G G et al.. Differential ligand activation of estrogen receptors ERα and ERβ at AP1 sites. Science. 1997; 277 1508-1510
- 77 Jacobson D, Pribnow D, Herson P S, Maylie J, Adelman J P. Determinants contributing to estrogen-regulated expression of SK3. Biochem Biophys Res Commun. 2003; 303 660-668
- 78 Rønnekleiv O K, Kelly M J. Diversity of ovarian steroid signaling in the hypothalamus. Front Neuroendocrinol. 2005; 26 65-84
- 79 Bryant D N, Sheldahl L C, Marriott L K, Shapiro R A, Dorsa D M. Multiple pathways transmit neuroprotective effects of gonadal steroids. Endocrine. 2006; 29 199-207
- 80 Razandi M, Pedram A, Greene G L, Levin E R. Cell membrane and nuclear estrogen receptors (ERs) originate from a single transcript: studies of ERα and ERβ expressed in Chinese hamster ovary cells. Mol Endocrinol. 1999; 13 307-319
- 81 Boulware M I, Weick J P, Becklund B R, Kuo S P, Groth R D, Mermelstein P G. Estradiol activates group I and II metabotropic glutamate receptor signaling, leading to opposing influences on cAMP response element-binding protein. J Neurosci. 2005; 25 5066-5078
- 82 Pedram A, Razandi M, Levin E R. Nature of functional estrogen receptors at the plasma membrane. Mol Endocrinol. 2006; 20 1996-2009
- 83 Szegõ ÉM, Barabás K, Balog J et al.. Estrogen induces estrogen receptor α-dependent cAMP response element-binding protein phosphorylation via mitogen activated protein kinase pathway in basal forebrain cholinergic neurons in vivo. J Neurosci. 2006; 26 4104-4110
- 84 Singer C A, Figueroa-Masot X A, Batchelor R H, Dorsa D M. The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons. J Neurosci. 1999; 19 2455-2463
- 85 Dubal D B, Zhu H, Yu J et al.. Estrogen receptor alpha, not beta, is a critical link in estradiol-mediated protection against brain injury. Proc Natl Acad Sci USA. 2001; 98 1952-1957
- 86 Wade C B, Robinson S, Shapiro R A, Dorsa D M. Estrogen receptor (ER)alpha and ERbeta exhibit unique pharmacologic properties when coupled to activation of the mitogen-activated protein kinase pathway. Endocrinology. 2001; 142 2336-2342
- 87 Abraham I M, Han S K, Todman M G, Korach K S, Herbison A E. Estrogen receptor beta mediates rapid estrogen actions on gonadotropin-releasing hormone neurons in vivo. J Neurosci. 2003; 23 5771-5777
- 88 Qiu J, Bosch M A, Tobias S C et al.. Rapid signaling of estrogen in hypothalamic neurons involves a novel G protein-coupled estrogen receptor that activates protein kinase C. J Neurosci. 2003; 23 9529-9540
- 89 Lund T D, Hinds L R, Handa R J. The androgen 5α-dihydrotestosterone and its metabolite 5α-androstan-3β, 17 β-diol inhibit the hypothalamo-pituitary-adrenal response to stress by acting through estrogen receptor β-expressing neurons in the hypothalamus. J Neurosci. 2006; 26 1448-1456
- 90 Toran-Allerand C D. Estrogen and the brain: beyond ER-α, ER-β and 17β-estradiol. Ann NY Acad Sci. 2005; 1052 136-144
- 91 Qiu J, Bosch M A, Tobias S C et al.. G protein-coupled estrogen receptor is involved in hypothalamic control of energy homeostasis. J Neurosci. 2006; 26 5649-5655
- 92 Filardo E J, Thomas P. GPR30: a seven-transmembrane-spanning estrogen receptor that triggers EGF release. Trends Endocrinol Metab. 2005; 16 362-367
- 93 Funakoshi T, Yanai A, Shinoda K, Kawano M M, Mizukami Y. G protein-coupled receptor 30 is an estrogen receptor in the plasma membrane. Biochem Biophys Res Commun. 2006; 346 904-910
- 94 Toran-Allerand C D, Singh M, Setalo Jr G. Novel mechanisms of estrogen action in the brain: New players in an old story. Front Neuroendocrinol. 1999; 20 97-121
- 95 Toran-Allerand C D, Guan X, MacLusky N J et al.. A novel, plasma membrane-associated, putative estrogen receptor that is regulated during development and after ischemic brain injury. J Neurosci. 2002; 22 8391-8401
- 96 Singh M, Setalo Jr G, Guan X, Warren M, Toran-Allerand C D. Estrogen-induced activation of mitogen-activated protein kinase in cerebral cortical explants: convergence of estrogen and neurotrophin signaling pathways. J Neurosci. 1999; 19 1179-1188
- 97 Singh M, Setalo G J, Guan X, Frail D E, Toran-Allerand C D. Estrogen-induced activation of the mitogen-activated protein kinase cascade in the cerebral cortex of estrogen receptor-alpha knock-out mice. J Neurosci. 2000; 20 1694-1700
- 98 Lagrange A H, Rønnekleiv O K, Kelly M J. Modulation of G protein-coupled receptors by an estrogen receptor that activates protein kinase A. Mol Pharmacol. 1997; 51 605-612
- 99 Weatherill P J, Wilson A PM, Nicholson R I, Davies P, Wakeling A E. Interaction of the antioestrogen ICI 164,384 with the oestrogen receptor. J Steroid Biochem Mol Biol. 1988; 30 263-266
- 100 Thomas P, Pang Y, Filardo E J, Dong J. Identity of an estrogen membrane receptor coupled to a G-protein in human breast cancer cells. Endocrinology. 2005; 146 624-632
- 101 Filardo E J. Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer. J Steroid Biochem Mol Biol. 2002; 80 231-238
- 102 Filardo E J, Quinn J A, Bland K I, Frackelton A RJ. Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Mol Endocrinol. 2000; 14 1649-1660
- 103 Filardo E J, Quinn J A, Frackelton A RJ, Bland K I. Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attennation of the epidermal growth factor receptor-to-MAPK signaling axis. Mol Endocrinol. 2002; 16 70-84
- 104 Kelly M J, Levin E R. Rapid actions of plasma membrane estrogen receptors. Trends Endocrinol Metab. 2001; 12 152-156
- 105 Bi R, Foy M R, Vouimba R M, Thompson R F, Baudry M. Cyclic changes in estradiol regulate synaptic plasticity through the MAP kinase pathway. Proc Natl Acad Sci USA. 2001; 98 13391-13395
- 106 Cato A CB, Nestl A, Mink S. Rapid actions of steroid receptors in cellular signaling pathways. SciSTKE. 2002; Available at: http://www.stke.org/cgi/content/full/sigtrans;2002/138/re9
- 107 Yang S-H, Sharrocks A D, Whitmarsh A J. Transcriptional regulation by the MAP kinase signaling cascades. Gene. 2003; 320 3-21
- 108 Deisseroth K, Mermelstein P G, Xia H, Tsien R W. Signaling from synapse to nucleus: the logic behind the mechanisms. Curr Opin Neurobiol. 2003; 13 354-365
- 109 Bryant D N, Bosch M A, Rønnekleiv O K, Dorsa D M. 17β-estradiol rapidly enhances extracellular signal-regulated kinase 2 phosphorylation in the rat brain. Neuroscience. 2005; 133 343-352
- 110 Zhou Y, Watters J J, Dorsa D M. Estrogen rapidly induces the phosphorylation of the cAMP response element binding protein in rat brain. Endocrinology. 1996; 137 2163-2166
- 111 Gu G, Rojo A A, Zee M C, Yu J, Simerly R B. Hormonal regulation of CREB phosphorylation in the anteroventral periventricular nucleus. J Neurosci. 1996; 16 3035-3044
- 112 Watters J J, Dorsa D M. Transcriptional effects of estrogen on neuronal neurotensin gene expression involve cAMP/protein kinase A-dependent signaling mechanisms. J Neurosci. 1998; 18 6672-6680
- 113 Abraham I M, Todman M G, Korach K S, Herbison A E. Critical in vivo roles for classical estrogen receptors in rapid estrogen actions on intracellular signaling in mouse brain. Endocrinology. 2004; 145 3055-3061
- 114 Honda K, Sawada H, Kihara T et al.. Phosphatidylinositol 3-kinase mediates neuroprotection by estrogen in cultured cortical neurons. J Neurosci Res. 2000; 60 321-327
- 115 Alkayed N J, Goto S, Sugo N et al.. Estrogen and Bcl-2: gene induction and effect of transgene in experimental stroke. J Neurosci. 2001; 21 7543-7550
- 116 Jover T, Tanaka H, Calderone A et al.. Estrogen protects against global ischemia-induced neuronal death and prevents activation of apoptotic signaling cascades in the hippocampal CA1. J Neurosci. 2002; 22 2115-2124
- 117 Rau S W, Dubal D B, Bottner M, Wise P M. Estradiol differentially regulates c-Fos after focal cerebral ischemia. J Neurosci. 2003; 23 10487-10494
- 118 Bushnell C D, Hurn P, Colton C et al.. Advancing the study of stroke in women: summary and recommendations for future research from an NINDS-sponsored multidisciplinary working group. Stroke. 2006; 37 2387-2399
- 119 Dubal D B, Kashon M L, Pettigrew L C et al.. Estradiol protects against ischemic injury. J Cereb Blood Flow Metab. 1998; 18 1253-1258
- 120 Mendez P, Azcoitia I, Garcia-Segura L M. Interdependence of oestrogen and insulin-like growth factor-I in the brain: potential for analysing neuroprotective mechanisms. J Endocrinol. 2005; 185 11-17
- 121 Mannella P, Brinton R D. Estrogen receptor protein interaction with phosphatidylinositol 3-kinase leads to activation of phosphorylated akt and extracellular signal-regulated kinase 1/2 in the same population of cortical neurons: a unified mechanism of estrogen action. J Neurosci. 2006; 26 9439-9447
- 122 Zhao L, Wu T-W, Brinton R D. Estrogen receptor subtypes alpha and beta contribute to neuroprotection and increased Bcl-2 expression in primary hippocampal neurons. Brain Res. 2004; 1010 22-34
- 123 Dubal D B, Rau S W, Shughrue P J et al.. Differential modulation of estrogen receptors (ERs) in ischemic brain injury: a role for ERα in estradiol-mediated protection against delayed cell death. Endocrinology. 2006; 147 3076-3084
- 124 Quesada A, Etgen A M. Insulin-like growth factor-1 regulation of α1-adrenergic receptor signaling is estradiol dependent in the preoptic area and hypothalamus of female rats. Endocrinology. 2001; 142 599-607
- 125 Cardona-Gómez G P, Mendez P, Garcia-Segura L M. Synergistic interaction of estradiol and insulin-like growth factor-I in the activation of PI3K/Akt signaling in the adult rat hypothalamus. Brain Res Mol Brain Res. 2002; 107 80-88
- 126 Mendez P, Azcoitia I, Garcia-Segura L M. Estrogen receptor alpha forms estrogen-dependent multimolecular complexes with insulin-like growth factor receptor and phospatidylinositol 3-kinase in the adult rat brain. Brain Res Mol Brain Res. 2003; 112 170-176
- 127 Quesada A, Etgen A M. Functional interactions between estrogen and insulin-like growth factor-I in the regulation of α1B-Adrenoceptors and female reproductive function. J Neurosci. 2002; 22 2401-2408
- 128 Etgen A M, Acosta-Martinez M. Participation of growth factor signal transduction pathways in estradiol facilitation of female reproductive behavior. Endocrinology. 2003; 144 3828-3835
- 129 Apostolakis E M, Garai J, Lohmann J E, Clark J H, O'Malley B W. Epidermal growth factor activates reproductive behavior independent of ovarian steroids in female rodents. Mol Endocrinol. 2000; 14 1086-1098
- 130 Han S-K, Gottsch M L, Lee K J et al.. Activation of gonadotropin-releasing hormone neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. J Neurosci. 2005; 25 11349-11356
- 131 Smith J T, Popa S M, Clifton D K, Hoffman G E, Steiner R A. Kiss1 neurons in the forebrain as central processors for generating the preovulatory luteinizing hormone surge. J Neurosci. 2006; 26 6687-6694
- 132 Wagner E J, Rønnekleiv O K, Bosch M A, Kelly M J. Estrogen biphasically modifies hypothalamic GABAergic function concomitantly with negative and positive control of luteinizing hormone release. J Neurosci. 2001; 21 2085-2093
- 133 Jackson G L, Kuehl D. Gamma-aminobutyric acid (GABA) regulation of GnRH secretion in sheep. Reproduction. 2002; 59 15-24
- 134 Wintermantel T M, Campbell R E, Porteous R et al.. Definition of estrogen receptor pathway critical for estrogen positive feedback to gonadotropin-releasing hormone neurons and fertility. Neuron. 2006; 52 271-280
- 135 Wagner E J, Rønnekleiv O K, Kelly M J. The noradrenergic inhibition of an apamine-sensitive small conductance Ca2+ -activated K+ channel in hypothalamic γ-aminobutyric acid neurons: pharmacology, estrogen sensitivity and relevance to the control of the reproductive axis. J Pharmacol Exp Ther. 2001; 299 21-30
- 136 Stocker M, Krause M, Pedarzani P. An apamin-sensitive Ca2+-activated K+ current in hippocampal pyramidal neurons. Proc Natl Acad Sci USA. 1999; 96 4662-4667
- 137 Sah P, Davies P. Calcium-activated potassium currents in mammalian neurons. Clin Exp Pharmacol Physiol. 2000; 27 657-663
- 138 Condon T P, Rønnekleiv O K, Kelly M J. Estrogen modulation of the α1-adrenergic response of hypothalamic neurons. Neuroendocrinology. 1989; 50 51-58
- 139 Lagrange A H, Rønnekleiv O K, Kelly M J. Estradiol-17β and μ-opioid peptides rapidly hyperpolarize GnRH neurons: A cellular mechanism of negative feedback?. Endocrinology. 1995; 136 2341-2344
- 140 Kuiper G G, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JÅ. Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA. 1996; 93 5925-5930
- 141 Kallo I, Butler J A, Barkovics-Kallo M, Goubillon M L, Coen C W. Oestrogen receptor beta-immunoreactivity in gonadotropin releasing hormone-expressing neurones: regulation by oestrogen. J Neuroendocrinol. 2001; 13 741-748
- 142 Herbison A E, Pape J R. New evidence for estrogen receptors in gonadotropin-releasing hormone neurons. Front Neuroendocrinol. 2001; 22 292-308
- 143 Spergel D J, Kruth U, Hanley D F, Sprengel R, Seeburg P H. GABA-and glutamate activated channels in green fluorescent protein-tagged gonadotropin-releasing hormone neurons in transgenic mice. J Neurosci. 1999; 19 2037-2050
- 144 Suter K J, Song W J, Sampson T L et al.. Genetic targeting of green fluorescent protein to gonadotropin-releasing hormone neurons: characterization of whole-cell electrophysiological properties and morphology. Endocrinology. 2000; 141 412-419
- 145 Kato M, Ui-Tei K, Watanabe M, Sakuma Y. Characterization of voltage-gated calcium currents in gonadotropin-releasing hormone neurons tagged with green fluorescent protein in rats. Endocrinology. 2003; 144 5118-5125
- 146 Temple J L, Laing E, Sunder A, Wray S. Direct action of estradiol on gonadotropin-releasing hormone-1 neuronal activity via a transcription-dependent mechanism. J Neurosci. 2004; 24 6326-6333
- 147 Temple J L, Wray S. BSA-estrogen compounds differentially alter gonadotropin-releasing hormone-1 neuronal activity. Endocrinology. 2005; 146 558-563
- 148 Krege J H, Hodgin J B, Couse J F et al.. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci USA. 1998; 95 15677-15682
- 149 Dupont S, Krust A, Gansmuller A, Dierich A, Chambon P, Mark M. Effect of single and compound knockouts of estrogen receptors α (ERα) and β (ERβ) on mouse reproductive phenotypes. Development. 2000; 127 4277-4291
- 150 Ogawa S, Eng V, Taylor J, Lubahn D B, Korach K S, Pfaff D W. Roles of estrogen receptor-alpha gene expression in reproduction-related behaviors in female mice. Endocrinology. 1998; 139 5070-5081
- 151 Vasudevan N, Kow L M, Pfaff D W. Early membrane estrogenic effects required for full expression of slower genomic actions in a nerve cell line. Proc Natl Acad Sci USA. 2001; 98 12267-12271
- 152 Kow L M, Pfaff D W. The membrane actions of estrogens can potentiate their lordosis behavior-facilitating genomic actions. Proc Natl Acad Sci USA. 2004; 101 12354-12357
- 153 Milewicz A, Bidzinska B, Mikulski E, Demissie M, Tworowska U. Influence of obesity and menopausal status on serum leptin, cholecystokinin, galanin and neuropeptide Y levels. Gynecol Endocrinol. 2000; 14 196-203
- 154 Geary N. Estradiol, CCK and satiation. Peptides. 2001; 22 1251-1263
- 155 Poehlman E T. Menopause, energy expenditure, and body composition. Acta Obstet Gynecol Scand. 2002; 81 603-611
- 156 Ahdieh H B, Wade G N. Effects of hysterectomy on sexual receptivity, food intake, running wheel activity, and hypothalamic estrogen and progestin receptors in rats. J Comp Physiol Psychol. 1982; 96 886-892
- 157 Colvin G B, Sawyer C H. Induction of running activity by intracerebral implants of estrogen in overiectomized rats. Neuroendocrinology. 1969; 4 309-320
- 158 Shimomura Y, Shimizu H, Takahashi M et al.. The significance of decreased ambulatory activity during the generation by long-term observation of obesity in ovariectomized rats. Physiol Behav. 1990; 47 155-159
- 159 Asarian L, Geary N. Cyclic estradiol treatment normalizes body weight and restores physiological patterns of spontaneous feeding and sexual receptivity in ovariectomized rats. Horm Behav. 2002; 42 461-471
- 160 Czaja J A, Goy R W. Ovarian hormones and food intake in female guinea pigs and rhesus monkeys. Horm Behav. 1975; 6 329-349
- 161 Butera P C, Czaja J A. Intracranial estradiol in ovariectomized guinea pigs: effects on ingestive behaviors and body weight. Brain Res. 1984; 322 41-48
- 162 Czaja J A. Sex differences in the activational effects of gonadal hormones on food intake and body weight. Physiol Behav. 1984; 33 553-558
- 163 McCaffrey T A, Czaja J A. Diverse effects of estradiol-17 beta: concurrent suppression of appetite, blood pressure and vascular reactivity in conscious, unrestrained animals. Physiol Behav. 1989; 45 649-657
- 164 Jones M EE, Thorburn A W, Britt K L et al.. Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. Proc Natl Acad Sci USA. 2000; 97 12735-12740
- 165 Thornton J E, Loose M D, Kelly M J, Rønnekleiv O K. Effects of estrogen on the number of neurons expressing β-endorphin in the medial basal hypothalamus of the female guinea pig. J Comp Neurol. 1994; 341 68-77
- 166 Bethea C L, Hess D L, Widmann A A, Henningfeld J M. Effects of progesterone on prolactin, hypothalamic beta-endorphin, hypothalamic substance P, and midbrain serotonin in guinea pigs. Neuroendocrinology. 1995; 61 695-703
- 167 Leal S, Andrade J P, Paula-Barbosa M M, Madeira M D. Arcuate nucleus of the hypothalamus: effects of age and sex. J Comp Neurol. 1998; 401 65-88
- 168 Shimizu H, Ohtani K, Kato Y, Tanaka Y, Mori M. Withdrawal of [corrected] estrogen increases hypothalamic neuropeptide Y (NPY) mRNA expression in ovariectomized obese rat. Neurosci Lett. 1996; 204 81-84
- 169 Hayward M D, Pintar J E, Low M J. Selective reward deficit in mice lacking β-endorphin and enkephalin. J Neurosci. 2002; 22 8251-8258
- 170 Appleyard S M, Hayward M, Young J I et al.. A role for the endogenous opioid beta-endorphin in energy homeostasis. Endocrinology. 2003; 144 1753-1760
- 171 Loose M D, Rønnekleiv O K, Kelly M J. Membrane properties and response to opioids of identified dopamine neurons in the guinea pig hypothalamus. J Neurosci. 1990; 10 3627-3634
- 172 Kelly M J, Loose M D, Rønnekleiv O K. Estrogen suppresses μ-opioid and GABAB-mediated hyperpolarization of hypothalamic arcuate neurons. J Neurosci. 1992; 12 2745-2750
- 173 Lagrange A H, Rønnekleiv O K, Kelly M J. The potency of μ-opioid hyperpolarization of hypothalamic arcuate neurons is rapidly attenuated by 17β-estradiol. J Neurosci. 1994; 14 6196-6204
- 174 Lagrange A H, Wagner E J, Rønnekleiv O K, Kelly M J. Estrogen rapidly attenuates a GABAB response in hypothalamic neurons. Neuroendocrinology. 1996; 64 114-123
Oline K RønnekleivPh.D.
Department of Physiology and Pharmacology, L334 Oregon Health & Science University
3181 S.W. Sam Jackson Park Road, Portland, OR 97239-3098
eMail: ronnekle@ohsu.edu