Chronic administration of androgens with actions at estrogen receptor beta have anti-anxiety and cognitive-enhancing effects in male rats.
Androgen levels decline with aging. Some androgens may exert anti-anxiety and cognitive-enhancing effects; however, determining which androgens have anxiolytic-like and/or mnemonic effects is of interest given the different mechanisms that may underlie some of their effects. For example, the 5 alpha-reduced metabolite of testosterone (T), dihydrotesterone, can be further converted to 5 alpha-androstane,17beta-diol-3 alpha-diol (3 alpha-diol) and 5 alpha-androstane,17beta-diol-3beta-diol (3beta-diol), both of which bind with high affinity to the beta isomer of the intracellular estrogen receptor beta (ER beta). However, androsterone, another metabolite of T, does not bind well to ER beta. To investigate the effects of T metabolites, male rats were subjected to gonadectomy then implanted with silastic capsules of 3 alpha-diol, 3beta-diol, androsterone, or oil control. After recovery, the rats were tested in elevated plus maze (EPM), light/dark transition (LD), and Morris water maze (MWM). 3 alpha-diol both decreased anxiety-like behavior in the EPM and LD, and increased cognition in MWM, while 3beta-diol improved cognition in MWM, but had no effects on anxiety behavior, compared to vehicle or androsterone. These data suggest that the actions of 3 alpha-diol and 3beta-diol at ER beta may be responsible for some of testosterone's anti-anxiety and cognitive-enhancing effects.
Osborne
Danielle M
DM
Department of Psychology, The University at Albany-SUNY, Albany, NY 12222, USA.
Edinger
Kassandra
K
Frye
Cheryl A
CA
JAMA. 2006 Nov 15;296(19):2351-61
17105798
Pharmacol Biochem Behav. 2004 Jul;78(3):523-9
15251261
Psychoneuroendocrinology. 2005 Jun;30(5):418-30
15721054
J Clin Endocrinol Metab. 1983 Jan;56(1):113-20
6183286
Horm Behav. 2006 Aug;50(2):216-22
16631174
Clin Cornerstone. 2005;7 Suppl 4:S8-12
16651207
Horm Behav. 1998 Apr;33(2):85-94
9647934
Behav Neurosci. 2004 Dec;118(6):1352-64
15598144
Neuroscience. 2006;138(3):1015-20
16310318
Psychoneuroendocrinology. 1998 May;23(4):385-99
9695138
Psychopharmacology (Berl). 2007 May;191(4):867-77
17211649
BJU Int. 2003 Aug;92(3):226-31
12887472
Cancer Res. 2005 Jun 15;65(12):5445-53
15958594
Neurobiol Learn Mem. 2007 Jan;87(1):78-85
16904920
Physiol Behav. 2007 Oct 22;92(3):443-53
17544460
Brain Res. 2002 May 10;935(1-2):73-80
12062475
Behav Brain Res. 2009 Jan 23;196(2):254-60
18926853
Horm Behav. 2008 May;53(5):741-52
18067894
Psychooncology. 2009 Mar;18(3):237-47
18636420
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3996-4001
11891272
Rev Urol. 2003;5 Suppl 1:S16-21
16985938
Pharmacol Biochem Behav. 2003 May;75(2):473-9
12873640
J Neurosci Methods. 1984 May;11(1):47-60
6471907
Cogn Affect Behav Neurosci. 2001 Dec;1(4):371-81
12467088
Psychiatr Dev. 1987 Spring;5(1):1-23
3601929
Behav Brain Res. 2002 Apr 15;132(1):85-93
11853861
Mol Cell Neurosci. 1994 Dec;5(6):549-55
7704428
Pharmacol Biochem Behav. 2000 Nov;67(3):587-96
11164090
Horm Behav. 1998 Oct;34(2):126-39
9799623
Endocrinology. 1990 Feb;126(2):1165-72
2298157
Curr Drug Targets CNS Neurol Disord. 2003 Aug;2(4):233-9
12871033
J Steroid Biochem. 1983 Feb;18(2):121-5
6843115
Psychoneuroendocrinology. 2005 Sep;30(8):762-70
15919582
Horm Res. 2001;56 Suppl 1:86-92
11786693
Behav Neurosci. 2008 Oct;122(5):974-81
18823154
Horm Behav. 1993 Dec;27(4):568-83
8294123
Psychopharmacology (Berl). 2007 Mar;191(1):119-25
17096081
J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):261-6
17113983
Best Pract Res Clin Endocrinol Metab. 2008 Apr;22(2):389-402
18471794
Behav Neurosci. 1994 Apr;108(2):325-32
8037876
Fertil Steril. 2008 Jul;90(1):165-73
18001721
Psychoneuroendocrinology. 1991;16(4):323-34
1745699
Neurotoxicol Teratol. 2009 Jan-Feb;31(1):1-10
18930132
Neuropsychopharmacology. 2005 Sep;30(9):1598-609
15798780
Psychoneuroendocrinology. 2003 Oct;28(7):863-74
12892654
Aging Male. 2002 Mar;5(1):47-51
12040975
Mol Neurobiol. 1988 Winter;2(4):291-317
2855977
Behav Brain Res. 2001 Aug 27;123(1):65-76
11377730
Cancer Epidemiol Biomarkers Prev. 2005 Sep;14(9):2257-60
16172240
Biol Reprod. 1987 Oct;37(3):628-33
3676409
Pharmacol Biochem Behav. 2004 Jul;78(3):559-68
15251265
Pharmacol Biochem Behav. 1999 Dec;64(4):777-85
10593201
Curr Med Chem. 2007;14(25):2680-701
17979718
Neuropsychopharmacology. 2008 Apr;33(5):1049-61
17625503