G-protein coupled estrogen receptor, estrogen receptor α, and progesterone receptor immunohistochemistry in the hypothalamus of aging female rhesus macaques given long-term estradiol treatment

Journal of Experimental Zoology Part A: Ecological Genetics and Physiology

Volumn 321, Issue 7, 2014, Pages 399-414

  Naugle, Michelle M ^a   Nguyen, Long T ^a   Merceron, Tyler K ^a   Filardo, Edward ^b   Janssen, William G M ^c   Morrison, John H ^c   Rapp, Peter R ^d   Gore, Andrea C ^a  

^a UNIVERSITY OF TEXAS AT AUSTIN   (United States)

^b BROWN UNIVERSITY   (United States)

^c MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^d NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ESTRADIOL; ESTROGEN; ESTROGEN RECEPTOR ALPHA; G PROTEIN COUPLED RECEPTOR; PROGESTERONE RECEPTOR;

AGING; ANIMAL; DRUG ADMINISTRATION; FEMALE; GENETICS; IMMUNOHISTOCHEMISTRY; METABOLISM; RHESUS MONKEY;

AGING; ANIMALS; DRUG ADMINISTRATION SCHEDULE; ESTRADIOL; ESTROGEN RECEPTOR ALPHA; ESTROGENS; FEMALE; IMMUNOHISTOCHEMISTRY; MACACA MULATTA; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, PROGESTERONE;

EID: 84903764582     PISSN: 19325223     EISSN: 19325231     Source Type: Journal    
DOI: 10.1002/jez.1871     Document Type: Article

References (115)

1. Abel TYW, Rance NE. 1999. Proopiomelanocortin gene expression is decreased in the infundibular nucleus of postmenopausal women. Brain Res Mol Brain Res 69:202-208.
2. Abrahám IM, Han SK, Todman MG, Korach KS, Herbison AE. 2003. Estrogen receptor beta mediates rapid estrogen actions on gonadotropin-releasing hormone neurons in vivo. J Neurosci 23:5771-5777.
3. Adams MM, Fink SE, Shah RA, Janssen WGM, Hayashi S, Milner TA, McEwen BS, Morrison JH. 2002. Estrogen and aging affect the subcellular distribution of estrogen receptor alpha in the hippocampus of female rats. J Neurosci 22:3608-3614.
4. Archer DF. 2004. Role of the nonhuman primate for research related to women's health. ILAR J 45:212-219.
5. Baulieu EE, Robel P. 1990. Neurosteroids: a new brain function? J Steroid Biochem Mol Biol 37:395-403.
6. Benjamini Y, Hochberg Y. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc Series B (Methodological) 57:289-300.
7. Bethea CL, Fahrenbach WH. 1992. Immunocytochemical localization of progestin receptors in monkey hypothalamus: effect of estrogen and progestin. Endocrinology 130:895-905.
8. Bethea CL, Brown NA, Kohama SG. 1996. Steroid regulation of estrogen and progestin receptor messenger ribonucleic acid in monkey hypothalamus and pituitary. Endocrinology 137:4372-4383.
9. Blaustein JD. 1993. Estrogen receptor immunoreactivity in rat brain: rapid effects of estradiol injection. Endocrinology 132:1218-1224.
10. Blaustein JD, Turcotte JC. 1989. Estradiol-induced progestin receptor immunoreactivity is found only in estrogen receptor-immunoreactive cells in guinea pig brain. Neuroendocrinology 49:454-461.
11. Bleier R. 1984. Hypothalamus of the rhesus monkey: a cytoarchitectonic atlas. Madison, WI: University of Wisconsin Press.
12. Blurton-Jones MM, Roberts JA, Tuszynski MH. 1999. Estrogen receptor immunoreactivity in the adult primate brain: neuronal distribution and association with p75, trkA, and choline acetyltransferase. J Comp Neurol 405:529-542.
13. Brailoiu E, Dun SL, Brailoiu GC, Mizuo K, Sklar LA, Oprea TI, Prossnitz ER, Dun NJ. 2007. Distribution and characterization of estrogen receptor G protein-coupled receptor 30 in the rat central nervous system. J Endocrinol 193:311-321.
14. Burger HG, Dudley EC, Robertson DM, Dennerstein L. 2002. Hormonal changes in the menopause transition. Recent Prog Horm Res 57:257-275.
15. Canonaco M, Giusi G, Madeo A, Facciolo RM, Lappano R, Canonaco A, Maggiolini M. 2008. A sexually dimorphic distribution pattern of the novel estrogen receptor G-protein-coupled receptor 30 in some brain areas of the hamster. J Endocrinol 196:131-138.
16. Canonico M, Plu-Bureau G, Lowe GDO, Scarabin P-Y. 2008. Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis. Br Med J 336:1227-1231.
17. Castellanoa JM, Bentsend AH, Mikkelsend JD, Tena-Sempere M. 2010. Kisspeptins: bridging energy homeostasis and reproduction. Brain Res 1364:129-138.
18. Chakraborty TR, Gore AC. 2004. Aging-related changes in ovarian hormones, their receptors, and neuroendocrine function. Exp Biol Med 229:977-987.
19. Chakraborty T, Hof P, Ng L, Gore AC. 2003. Stereologic analysis of estrogen receptor alpha (ERα) expression in rat hypothalamus and its regulation by aging and estrogen. J Comp Neurol 466:409-421.
20. Dorling AA, Todman MG, Korach KS, Herbison AE. 2003. Critical role for estrogen receptor alpha in negative feedback regulation of gonadotropin-releasing hormone mRNA expression in the female mouse. Neuroendocrinology 78:204-209.
21. Downs JL, Wise PM. 2009. The role of the brain in female reproductive aging. Mol Cell Endocrinol 299:32-38.
22. Filardo EJ, Thomas P. 2012. Minireview: G protein-coupled estrogen receptor-1, GPER-1: its mechanism of action and role in female reproductive cancer, renal and vascular physiology. Endocrinology 153:2953-2962.
23. Filardo EJ, Quinn JA, Bland KL, Frackelton AR. 2000. 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 14:1649-1660.
24. Filardo EJ, Quinn JA, Frackelton AR, Bland KI. 2002. Estrogen action via the G protein-coupled receptor, GPR30: stimulation of adenylyl cyclase and cAMP-mediated attenuation of the epidermal growth factor receptor-to-MAPK signaling axis. Mol Endocrinol 16:70-84.
25. Filardo EJ, Quinn J, Pang Y, Graeber C, Shaw S, Dong J, Thomas P. 2007. Activation of the novel estrogen receptor G protein-coupled receptor 30 (GPR30) at the plasma membrane. Endocrinology 148:3236-3245.
26. Fitzpatrick LA, Pace C, Wiita B. 2000. Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey. J Womens Health Gend Based Med 9:381-387.
27. Fox J, Weisberg S. 2011. An {R} companion to applied regression. Thousand Oaks, CA: Sage Publishers.
28. Funabashi T, Kleopoulos SP, Brooks PJ, Kimura F, Pfaff DW, Shinohara K, Mobbs CV. 2000. Changes in estrogenic regulation of estrogen receptor a mRNA and progesterone receptor mRNA in the female rat hypothalamus during aging: an in situ hybridization study. Neurosci Res 38:85-92.
29. Furuta M, Fukushima A, Chiba S, Sano A, Akema T, Kimura F, Funabashi T. 2010. Progesterone receptor immunoreactivity in the brains of ovariectomized aged rats. Neuroreport 21:777-781.
30. Fuxjager MJ, Forbes-Lorman RM, Coss DJ, Auger CJ, Auger AP, Marler CA. 2010. Winning territorial disputes selectively enhances androgen sensitivity in neural pathways related to motivation and social aggression. Proc Natl Acad Sci USA 107:12393-12398.
31. Gilardi KV, Shideler SE, Valverde CR, Roberts JA, Lasley BL. 1997. Characterization of the onset of menopause in the rhesus macaque. Biol Reprod 57:335-340.
32. Gill S, Lavoie HB, Bo-Abbas Y, Hall JE. 2002a. Negative feedback effects of gonadal steroids are preserved with aging in postmenopausal women. J Clin Endocrinol Metab 87:2297-2302.
33. Gill S, Sharpless JL, Rado K, Hall JE. 2002b. Evidence that GnRH decreases with gonadal steroid feedback but increases with age in postmenopausal women. J Clin Endocrinol Metab 87:2290-2296.
34. Glaser EM, Wilson PD. 1998. The coefficient of error of optical fractionator population size estimates: a computer simulation comparing three estimators. J Microsc 192:163-171.
35. Glidewell-Kenney C, Hurley LA, Pfaff L, Weiss J, Levine JE, Jameson JL. 2007. Nonclassical estrogen receptor alpha signaling mediates negative feedback in the female mouse reproductive axis. Proc Natl Acad Sci USA 104:8173-8177.
36. Gore AC, Oung T, Yung S, Flagg RA, Woller MJ. 2000. Neuroendocrine mechanisms for reproductive senescence in the rat: gonadotropin-releasing hormone neurons. Endocrinology 13:315-323.
37. Gore AC, Windsor-Engnell BM, Terasawa E. 2004. Menopausal increases in pulsatile gonadotropin-releasing hormone release in a nonhuman primate (Macaca mulatta). Endocrinology 145:4653-4659.
38. Gorosito SV, Lorenzo AG, Cambiasso MJ. 2008. Estrogen receptor alpha is expressed on the cell-surface of embryonic hypothalamic neurons. Neuroscience 154:1173-1177.
39. Gougeon A, Ecochard R, Thalabard JC. 1994. Age-related changes of the population of human ovarian follicles: increase in the disappearance rate of non-growing and early-growing follicles in aging women. Biol Reprod 50:653-663.
40. Gundersen HJG, Jensen EB. 1987. The efficiency of systematic sampling in stereology and its prediction. J Microsc 147:229-263.
41. Gundersen HJG, Bagger P, Bendtsen TF, Evans SM, Korbo L, Marcussen N, Møller A, Nielsen K, Nyengaard JR, Pakken-Berg B, Sørensen AFB, Vesterby A, West MJ. 1988. The new stereological tools: disector, fractionator, nucleator and point sample intercepts and their use in pathological research and diagnosis. APMIS 96:857-881.
42. Gundlah C, Kohama SG, Mirkes SJ, Garyfallou VT, Urbanski HF, Bethea CL. 2000. 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 76:191-204.
43. Hall JE. 2007. Neuroendocrine changes with reproductive aging in women. Semin Reprod Med 25:344-351.
44. Hammond R, Nelson D, Gibbs RB. 2011. GPR30 co-localizes with cholinergic neurons in the basal forebrain and enhances potassium-stimulated acetylcholine release in the hippocampus. Psychoneuroendocrinology 36:182-192.
45. Hao J, Janssen WG, Tang Y, Roberts JA, McKay H, Lasley B, Allen PB, Greengard P, Rapp PR, Kordower JH, Hof PR, Morrison JH. 2003. Estrogen increases the number of spinophilin-immunoreactive spines in the hippocampus of young and aged female rhesus monkeys. J Comp Neurol 465:540-550.
46. Hao J, Rapp PR, Leffler AE, Leffler SR, Janssen WGM, Lou W, McKay H, Roberts JA, Wearne SL, Hof PR, Morrison JH. 2006. Estrogen alters spine number and morphology in prefrontal cortex of aged female rhesus monkeys. J Neurosci 26:2571-2578.
47. Hao J, Rapp PR, Janssen WGM, Lou W, Lasley BL, Hof PR, Morrison JH. 2007. Interactive effects of age and estrogen on cognition and pyramidal neurons in monkey prefrontal cortex. Proc Natl Acad Sci USA 104:11465-11470.
48. Hazell G, Yao S, Roper J, Prossnitz E, O'Carroll A, Lolait S. 2009. Localisation of GPR30, a novel G protein-coupled oestrogen receptor, suggests multiple functions in rodent brain and peripheral tissues. J Endocrinol 202:223-236.
49. Herrinton LJ, Weiss NS. 1993. Postmenopausal unopposed estrogens characteristics of use in relation to the risk of endometrial carcinoma. Ann Epidemiol 3:308-318.
50. Hochberg Y, Benjamini Y. 1990. More powerful procedures for multiple significance testing. Stat Med 9:811-818.
51. Hofman M. 1997. Lifespan changes in the human hypothalamus. Exp Gerontol 32:559-575.
52. Hrabovszky E, Steinhauser A, Barabás K, Shughrue PJ, Petersen SL, Merchenthaler I, Liposits Z. 2001. Estrogen receptor-beta immunoreactivity in luteinizing hormone-releasing hormone neurons of the rat brain. Endocrinology 142:3261-3264.
53. Inoue T. 2002. Progesterone production and actions in the human central nervous system and neurogenic tumors. J Clin Endocrinol Metab 87:5325-5331.
54. Kaplan JR. 2004. Modeling women's health with nonhuman primates and other animals. ILAR J 45:83-88.
55. Kenealy BP, Keen KL, Ronnekleiv OK, Terasawa E. 2011a. STX, a novel nonsteroidal estrogenic compound, induces rapid action in primate GnRH neuronal calcium dynamics and peptide release. Endocrinology 152:3182-3191.
56. Kenealy BP, Keen KL, Terasawa E. 2011b. Rapid action of estradiol in primate GnRH neurons: the role of estrogen receptor alpha and estrogen receptor beta. Steroids 76:861-866.
57. Kermath BA, Gore AC. 2012. Neuroendocrine control of the natural transition to reproductive senescence. Neuroendocrinology 96:1-12.
58. Korbo L, Andersen BB. 1995. The distributions of Purkinje cell perikaryon and nuclear volume in human and rat cerebellum with the nucleator method. Neuroscience 69:151-158.
59. Krey LC, Butler WR, Knobil E. 1975. Surgical disconnection of the medial basal hypothalamus and pituitary function in the rhesus monkey. I Gonadotropin secretion. ILAR J 96:1073-1087.
60. Kruskal W, Wallis WA. 1952. Use of ranks in one-criterion variance analysis. J Am Stat Assoc 47:582-621.
61. Kurnick NB. 1950. Methyl green-pyronin; basis of selective staining of nucleic acids. J Gen Physiol 33:243-264.
62. Lauber AH, Mobbs CV, Muramatsu M, Pfaff DW. 1991. Estrogen receptor messenger RNA expression in rat hypothalamus as a function of genetic sex and estrogen dose. Endocrinology 129:3180-3186.
63. Liu JH, Yen SS. 1983. Induction of midcycle gonadotropin surge by ovarian steroids in women: a critical evaluation. J Clin Endocrinol Metab 57:797-802.
64. Long X, Nephew KP. 2006. Fulvestrant (ICI 182, 780)-dependent interacting proteins mediate immobilization and degradation of estrogen receptor-alpha. J Biol Chem 281:9607-9615.
65. Lubahn DB, Moyer JS, Golding TS, Couse JF, Korach KS, Smithies O. 1993. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci USA 90:11162-11166.
66. Lydon JP, DeMayo FJ, Conneely OM, O'Malley BW. 1996. Reproductive phenotypes of the progesterone receptor null mutant mouse. J Steroid Biochem Mol Biol 56:67-77.
67. Maffucci JA, Gore AC. 2006. Age-related changes in hormones and their receptors in animal models of female reproductive senescence. In: Conn PM, editor. Handbook of models for human aging. New York, NY: Academic Press/Elsevier. p 533-552.
68. Manson JE, Chlebowski RT, Stefanick ML, Aragaki AK, Rossouw JE, Prentice RL, Anderson G, Howard BV, Thomson CA, LaCroix AZ, Wactawski-Wende J, Jackson RD, Limacher M, Margolis KL, Wassertheil-Smoller S, Beresford SA, Cauley JA, Eaton CB, Gass M, Hsia J, Johnson KC, Kooperberg C, Kuller LH, Lewis CE, Liu S, Martin LW, Ockene JK, O'Sullivan MJ, Powell LH, Simon MS, Van Horn L, Vitolins MZ, Wallace RB. 2013. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA 310:1353-1368.
69. McEwen BS. 2002. Estrogen actions throughout the brain. Recent Prog Horm Res 57:357-384.
70. Michael RP, Clancy AN, Zumpe D. 2005. Mating activates estrogen receptor-containing neurons in the female monkey brain. Physiol Behav 85:404-413.
71. Mills RH, Romeo HE, Lu JKH, Micevych PE. 2002. Site-specific decrease of progesterone receptor mRNA expression in the hypothalamus of middle-aged persistently estrus rats. Brain Res 955:200-206.
72. Mittelman-Smith MA, Williams H, Krajewski-Hall SJ, McMullen NT, Rance NE. 2012. Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature. Proc Natl Acad Sci USA 109:19846-19851.
73. Noel SD, Keen KL, Baumann DI, Filardo EJ, Terasawa E. 2009. Involvement of G protein-coupled receptor 30 (GPR30) in rapid action of estrogen in primate LHRH neurons. Mol Endocrinol 23:349-359.
74. Olster DH. 1998. Lordosis-enhancing medial preoptic area lesions do not alter hypothalamic estrogen receptor- or progestin receptor-immunoreactivity in prepubertal female guinea pigs. Brain Res 790:254-263.
75. Oriowo MA, Landgren BM, Stenstrom B, Diczfalusy E. 1980. A comparison of the pharmacokinetic properties of three estradiol esters. Contraception 21:415-424.
76. Pau CY, Pau KY, Spies HG. 1998. Putative estrogen receptor beta and alpha mRNA expression in male and female rhesus macaques. Mol Cell Endocrinol 146:59-68.
77. Paxinos G, Huang X-F, Toga A. 1990. The rhesus monkey brain in stereotaxic coordinates. San Diego, CA: Academic Press.
78. Petersen SL, Ottem EN, Carpenter CD. 2003. Direct and indirect regulation of gonadotropin-releasing hormone neurons by estradiol. Biol Reprod 69:1771-1778.
79. Prentice RL, Manson JE, Langer RD, Anderson GL, Pettinger M, Jackson RD, Johnson KC, Kuller LH, Lane DS, Wactawski-Wende J, Brzyski R, Allison M, Ockene J, Sarto G, Rossouw JE. 2009. Benefits and risks of postmenopausal hormone therapy when it is initiated soon after menopause. Am J Epidemiol 170:12-23.
80. Prossnitz ER, Barton M. 2011. The G-protein-coupled estrogen receptor GPER in health and disease. Nat Rev Endocrinol 7:715-726.
81. Quadros PS, Wagner CK. 2008. Regulation of progesterone receptor expression by estradiol is dependent on age, sex and region in the rat brain. Endocrinology 149:3054-3061.
82. Quadros PS, Schlueter LJ, Wagner CK. 2008. Distribution of progesterone receptor immunoreactivity in the midbrain and hindbrain of postnatal rats. Dev Neurobiol 68:1378-1390.
83. R Development Core Team. 2012. R: A language and environment for statistical computing. Vienna, Austria.
84. Rahimy MH, Ryan KK, Hopkins NK. 1999. Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension): steady-state pharmokinetics of MPA and E2 in surgically sterile women. Contraception 60:209-214.
85. Rance NE. 2009. Menopause and the human hypothalamus: evidence for the role of kisspeptin/neurokinin B neurons in the regulation of estrogen negative feedback. Peptides 30:111-122.
86. Rance NE, McMullen NT, Smiaek JE, Price DL, Young WS III. 1990. Postmenopausal hypertrophy of neurons expressing the estrogen receptor gene in the human hypothalamus. J Clin Endocrinol Metab 71:79-85.
87. Rapp PR, Morrison JH, Roberts JA. 2003. Cyclic estrogen replacement improves cognitive function in aged ovariectomized rhesus monkeys. J Neurosci 23:5708-5714.
88. Richardson SJ, Senikas V, Nelson JF. 1987. Follicular depletion during the menopausal transition: evidence for accelerated loss and ultimate exhaustion. J Clin Endocrinol Metab 65:1231-1237.
89. Roberts DE, Killiany RJ, Rosene DL. 2012. Neuron numbers in the hypothalamus of the normal aging rhesus monkey: stability across the adult lifespan and between the sexes. J Comp Neurol 520:1181-1197.
90. Rometo AM, Rance NE. 2008. Changes in prodynorphin gene expression and neuronal morphology in the hypothalamus of postmenopausal women. J Neuroendocrinol 20:1376-1381.
91. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J, Writing Group for the Women's Health Initiative Investigators. 2002. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 288:321-333.
92. Shapiro SS, Wilk MB. 1965. An analysis of variance test for normality (complete samples). Biometrika 52:591-611.
93. Sharma G, Prossnitz ER. 2011. Mechanisms of estradiol-induced insulin secretion by the G protein-coupled estrogen receptor GPR30/GPER in pancreatic beta-cells. Endocrinology 152:3030-3039.
94. Shaw ND, Srouji SS, Histed N, Hall JE. 2011. Differential effects of aging on estrogen negative and positive feedback. Am J Physiol Endocrinol Metab 301:351-355.
95. Shideler SE, Gee NA, Chen J, Laughlin LS, Rapp PR, Morrison JH, Roberst JA, Moran FM, Lasley BL. 2003. Contribution of ovarian steroid production to urinary estrone conjugate concentrations in Macaca mulatta. Am J Primatol 61:111-121.
96. Shughrue PJ, Bushnell CD, Dorsa DM. 1992. Estrogen receptor messenger ribonucleic acid in female rat brain during the estrous cycle: a comparison with ovariectomized females and intact males. Endocrinology 131:381-388.
97. Skinner DC, Evans NP, Delaleu B, Goodman RL, Bouchard P, Caraty A. 1998. The negative feedback actions of progesterone on gonadotropin-releasing hormone secretion are transduced by the classical progesterone receptor. Proc Natl Acad Sci USA 95:10978-10983.
98. Snyder MA, Smejkalova T, Forlano PM, Woolley CS. 2010. Multiple ER(beta) antisera label in ER(beta) knockout and null mouse tissues. J Neurosci Methods 188:226-234.
99. Sullivan KA, Witkin JW, Ferin M, Silverman AJ. 1995. Gonadotropin-releasing hormone neurons in the rhesus macaque are not immunoreactive for the estrogen receptor. Brain Res 685:198-200.
100. Talboom JS, Williams BJ, Baxley ER, West SG, Bimonte-Nelson HA. 2008. Higher levels of estradiol replacement correlate with better spatial memory in surgically menopausal young and middle-aged rats. Neurobiol Learn Mem 90:155-163.
101. Terasawa E. 1995. Control of luteinizing hormone-releasing hormone pulse generation in nonhuman primates. Cell Mol Neurobiol 15:141-164.
102. Terauchi M, Honjo H, Mizunuma H, Aso T. 2012. Effects of oral estradiol and levonorgestrel on cardiovascular risk markers in postmenopausal women. Arch Gynecol Obstet 285:1647-1656.
103. Trévoux R, De Brux J, Castanier M, Nahoul K, Soule JP, Scholler R. 1986. Endometrium and plasma hormone profile in the peri-menopause and post-menopause. Maturitas 8:309-326.
104. Tsai H-W, LaPolt PS, Olcott AP, Lu JKH. 2004. Temporal changes occur in the neuroendocrine control of gonadotropin secretion in aging female rats: role of progesterone. Biol Reprod 71:845-852.
105. Ule G, Schwechheimer K, Tschahargane C. 1983. Morphological feedback effect on neurons of the nucl. arcuatus (sive infundibularis) and nucl. subventricularis hypothalami due to gonadal atrophy. Virchows Arch A Pathol Anat Histopathol 400:297-308.
106. Van Look PF, Lothian H, Hunter WM, Michie EA, Baird DT. 1977. Hypothalamic-pituitary-ovarian function in perimenopausal women. Clin Endocrinol (Oxf) 7:13-31.
107. Wang C, Dehghani B, Magrisso IJ, Rick EA, Bonhomme E, Cody DB, Elenich LA, Subramanian S, Murphy SJ, Kelly MJ, Rosenbaum JS, Vandenbark AA, Offner H. 2008. GPR30 contributes to estrogen-induced thymic atrophy. Mol Endocrinol 22:636-648.
108. Wang AC, Hara Y, Janssen WG, Rapp PR, Morrison JH. 2010. Synaptic estrogen receptor-alpha levels in prefrontal cortex in female rhesus monkeys and their correlation with cognitive performance. J Neurosci 30:12770-12776.
109. Weiss G, Skurnick JH, Goldsmith LT, Santoro NF, Park SJ. 2004. Menopause and hypothalamic-pituitary sensitivity to estrogen. JAMA 292:2991-2996.
110. West MJ, Slomianka L, Gundersen HJ. 1991. Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231:482-497.
111. Wiegand SJ, Terasawa E. 1982. Discrete lesions reveal functional heterogeneity of suprachiasmatic structures in regulation of gonadotropin secretion in the female rat. Neuroendocrinology 34:395-404.
112. Wilcoxon F. 1945. Individual comparisons by ranking methods. Biometrics 1:80-83.
113. Wilson ME, Rosewell KL, Kashon ML, Shughrue PJ, Merchenthaler I, Wise PM. 2002. Age differentially influences estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta) gene expression in specific regions of the rat brain. Mech Ageing Dev 123:593-601.
114. Wise PM. 1984. Estradiol-induced daily luteinizing hormone and prolactin surges in young and middle-aged rats: correlations with age-related changes in pituitary responsiveness and catecholamine turnover rates in microdissected brain areas. Endocrine 115:801-809.
115. Wise PM, Ratner A. 1980. Effect of ovariectomy on plasma LH, FSH, estradiol and progesterone and medial basal hypothalamic LHRH concentrations in old and young rats. Neuroendocrinology 30:15-19.