title: Androgens and spermatogenesis: lessons from transgenic mouse models.
abstract: Transgenic mouse models have contributed considerably to our understanding of the cellular and molecular mechanisms by which androgens control spermatogenesis. Cell-selective ablation of the androgen receptor (AR) in Sertoli cells (SC) results in a complete block in meiosis and unambiguously identifies the SC as the main cellular mediator of the effects of androgens on spermatogenesis. This conclusion is corroborated by similar knockouts in other potential testicular target cells. Mutations resulting in diminished expression of the AR or in alleles with increased length of the CAG repeat mimick specific human forms of disturbed fertility that are not accompanied by defects in male sexual development. Transcriptional profiling studies in mice with cell-selective and general knockouts of the AR, searching for androgen-regulated genes relevant to the control of spermatogenesis, have identified many candidate target genes. However, with the exception of Rhox5, the identified subsets of genes show little overlap. Genes related to tubular restructuring, cell junction dynamics, the cytoskeleton, solute transportation and vitamin A metabolism are prominently present. Further research will be needed to decide which of these genes are physiologically relevant and to identify genes that can be used as diagnostic tools or targets to modulate the effects of androgens in spermatogenesis.
authors.affiliation: Department of Experimental Medicine, Laboratory for Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. guido.verhoeven@med.kuleuven.be
authors.forename: Guido
authors.initials: G
authors.lastname: Verhoeven
authors.forename: Ariane
authors.initials: A
authors.lastname: Willems
authors.forename: Evi
authors.initials: E
authors.lastname: Denolet
authors.forename: Johannes V
authors.initials: JV
authors.lastname: Swinnen
authors.forename: Karel
authors.initials: K
authors.lastname: De Gendt
mesh_terms: D000728:Androgens / Q000235:genetics / Q000502:physiology*; D000818:Animals; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011944:Receptors, Androgen / Q000502:physiology; D012708:Sertoli Cells / Q000166:cytology / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000502:physiology*
chemical_list: D000728:Androgens; D011944:Receptors, Androgen
references.citation: Gene. 2002 Nov 13;301(1-2):1-11
references.pmid: 12490318
references.citation: Endocrinology. 2000 Aug;141(8):2779-85
references.pmid: 10919263
references.citation: Endocrinology. 1984 Oct;115(4):1248-55
references.pmid: 6090096
references.citation: J Reprod Fertil. 1994 May;101(1):193-8
references.pmid: 8064681
references.citation: Endocrinology. 2001 Jun;142(6):2213-20
references.pmid: 11356665
references.citation: Mol Endocrinol. 2000 Aug;14(8):1162-74
references.pmid: 10935541
references.citation: Endocrinology. 2004 Jan;145(1):318-29
references.pmid: 14551232
references.citation: J Androl. 2009 May-Jun;30(3):338-48
references.pmid: 19136388
references.citation: J Androl. 1999 May-Jun;20(3):399-406
references.pmid: 10386820
references.citation: Hum Reprod Update. 2004 Jul-Aug;10(4):349-69
references.pmid: 15192055
references.citation: Recent Prog Horm Res. 2002;57:149-79
references.pmid: 12017541
references.citation: Biol Reprod. 1976 Apr;14(3):332-8
references.pmid: 1252566
references.citation: J Androl. 1986 Jul-Aug;7(4):240-53
references.pmid: 3745011
references.citation: J Pathol. 2006 Mar;208(4):518-27
references.pmid: 16400621
references.citation: Nature. 1991 Jul 4;352(6330):77-9
references.pmid: 2062380
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1327-32
references.pmid: 14745012
references.citation: Endocrinology. 2005 Sep;146(9):4117-26
references.pmid: 15919750
references.citation: J Clin Invest. 1999 Jun;103(11):1517-25
references.pmid: 10359561
references.citation: Int J Androl. 1983 Jun;6(3):249-60
references.pmid: 6411627
references.citation: Mol Endocrinol. 2006 Feb;20(2):321-34
references.pmid: 16166195
references.citation: Endocrinology. 1994 May;134(5):2307-16
references.pmid: 8156934
references.citation: Endocrinology. 2005 Mar;146(3):1268-84
references.pmid: 15591133
references.citation: J Androl. 1998 Jan-Feb;19(1):21-30
references.pmid: 9537288
references.citation: Mol Endocrinol. 2004 Feb;18(2):422-33
references.pmid: 14605096
references.citation: Endocrinology. 1994 Sep;135(3):1227-34
references.pmid: 8070367
references.citation: Proc Natl Acad Sci U S A. 2004 May 4;101(18):6876-81
references.pmid: 15107499
references.citation: Endocrinology. 1988 Oct;123(4):2100-10
references.pmid: 2458250
references.citation: Biol Reprod. 2004 Nov;71(5):1605-13
references.pmid: 15253923
references.citation: Endocrinology. 1999 Sep;140(9):3938-46
references.pmid: 10465262
references.citation: Endocr Rev. 2007 Dec;28(7):778-808
references.pmid: 17940184
references.citation: Tissue Cell. 1998 Oct;30(5):583-8
references.pmid: 9839481
references.citation: Tissue Cell. 1981;13(2):369-80
references.pmid: 6458924
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3615-20
references.pmid: 17360691
references.citation: J Clin Endocrinol Metab. 2006 Oct;91(10):3962-9
references.pmid: 16895950
references.citation: Endocrinology. 2006 Jul;147(7):3563-70
references.pmid: 16627582
references.citation: Toxicol Sci. 2003 Dec;76(2):418-26
references.pmid: 14514963
references.citation: J Cell Sci. 1991 Nov;100 ( Pt 3):623-33
references.pmid: 1808210
references.citation: Mol Endocrinol. 2007 Apr;21(4):895-907
references.pmid: 17244764
references.citation: Anat Rec. 1993 Apr;235(4):547-59
references.pmid: 8385423
references.citation: J Clin Endocrinol Metab. 2007 Nov;92(11):4319-26
references.pmid: 17684052
references.citation: Endocr Rev. 1991 Feb;12(1):45-77
references.pmid: 2026122
references.citation: Clin Chem Lab Med. 1998 Aug;36(8):663-5
references.pmid: 9806482
references.citation: Ann N Y Acad Sci. 2007 Dec;1120:72-83
references.pmid: 18184911
references.citation: Biol Reprod. 2005 Apr;72(4):1010-9
references.pmid: 15601916
references.citation: Nat Genet. 1997 Feb;15(2):205-6
references.pmid: 9020851
references.citation: Proc Natl Acad Sci U S A. 1985 Jan;82(1):114-8
references.pmid: 3855533
references.citation: Biol Reprod. 1993 Dec;49(6):1215-28
references.pmid: 8286604
references.citation: Biol Reprod. 2003 Apr;68(4):1299-307
references.pmid: 12606480
references.citation: Mol Genet Metab. 2003 Mar;78(3):175-85
references.pmid: 12649062
references.citation: Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13612-7
references.pmid: 9811848
references.citation: Environ Health Perspect. 2008 Mar;116(3):269-77
references.pmid: 18335090
references.citation: Tissue Cell. 1994 Jun;26(3):375-83
references.pmid: 8073417
references.citation: Endocrinology. 2006 Dec;147(12):5624-33
references.pmid: 16973730
references.citation: Fertil Steril. 1977 Aug;28(8):818-22
references.pmid: 407105
references.citation: Endocrinology. 2007 Jun;148(6):2914-24
references.pmid: 17332066
references.citation: Biol Reprod. 2000 Jul;63(1):99-108
references.pmid: 10859247
references.citation: Endocr Rev. 1995 Jun;16(3):271-321
references.pmid: 7671849
references.citation: J Reprod Fertil. 1983 Mar;67(2):359-63
references.pmid: 6834332
references.citation: Anat Rec. 1977 Mar;187(3):347-66
references.pmid: 851237
references.citation: J Clin Endocrinol Metab. 2009 Jan;94(1):277-84
references.pmid: 18840639
references.citation: Int J Androl. 2003 Aug;26(4):195-201
references.pmid: 12846794
references.citation: FASEB J. 2009 Dec;23(12):4218-30
references.pmid: 19692648
references.citation: Endocrinology. 2005 Jun;146(6):2674-83
references.pmid: 15761038
references.citation: Endocrinology. 1995 Dec;136(12):5311-21
references.pmid: 7588276
references.citation: Eur J Endocrinol. 2002 Sep;147(3):425-33
references.pmid: 12213681
references.citation: Mol Endocrinol. 2004 Jul;18(7):1610-9
references.pmid: 15118069
references.citation: J Clin Endocrinol Metab. 2008 Nov;93(11):4408-12
references.pmid: 18713818
references.citation: Int J Gynecol Pathol. 1991;10(2):126-44
references.pmid: 2032766
references.citation: Biol Reprod. 1979 Aug;21(1):241-9
references.pmid: 486641
references.citation: J Clin Endocrinol Metab. 2001 Jun;86(6):2585-90
references.pmid: 11397858
references.citation: FASEB J. 2008 Jun;22(6):1945-59
references.pmid: 18192323
references.citation: Endocrinology. 1994 Dec;135(6):2608-14
references.pmid: 7988449
references.citation: Int Rev Cytol. 1993;147:25-96
references.pmid: 8225836
references.citation: Crit Rev Biochem Mol Biol. 2002;37(1):1-28
references.pmid: 11905545
references.citation: Clin Endocrinol (Oxf). 2002 Nov;57(5):647-55
references.pmid: 12390340
references.citation: Endocrinology. 2005 Mar;146(3):1192-204
references.pmid: 15591141
references.citation: J Clin Endocrinol Metab. 1999 Jan;84(1):350-8
references.pmid: 9920106
references.citation: J Biol Chem. 1988 Feb 25;263(6):2884-90
references.pmid: 3343234
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17718-23
references.pmid: 17095600
references.citation: Biol Reprod. 1998 Dec;59(6):1371-7
references.pmid: 9828180
references.citation: Development. 2004 Jan;131(2):459-67
references.pmid: 14701682
references.citation: Endocrinology. 2000 May;141(5):1795-803
references.pmid: 10803590
references.citation: Endocr Rev. 1982 Fall;3(4):404-17
references.pmid: 6295753
references.citation: Science. 2002 Jun 21;296(5576):2174-6
references.pmid: 12077400
references.citation: Annu Rev Biochem. 1994;63:25-61
references.pmid: 7979239
references.citation: Nat Genet. 2006 Dec;38(12):1362-3
references.pmid: 17133220
references.citation: Proc Soc Exp Biol Med. 1993 Apr;202(4):457-64
references.pmid: 8456111
references.citation: Endocr Rev. 2004 Oct;25(5):747-806
references.pmid: 15466940
references.citation: Endocr Rev. 1999 Jun;20(3):321-44
references.pmid: 10368774
references.citation: Endocr Res. 1996 Aug;22(3):197-219
references.pmid: 8875135
references.citation: Endocr Rev. 1993 Oct;14(5):577-93
references.pmid: 8262007
references.citation: J Clin Endocrinol Metab. 1984 Oct;59(4):785-9
references.pmid: 6480805
references.citation: Acta Endocrinol (Copenh). 1963 Dec;44:536-44
references.pmid: 14082542
references.citation: Biol Reprod. 2009 Dec;81(6):1083-92
references.pmid: 19587329
references.citation: Curr Top Dev Biol. 2005;71:263-96
references.pmid: 16344108
references.citation: Proc Natl Acad Sci U S A. 2002 May 14;99(10):7142-7
references.pmid: 11997476
references.citation: Nucl Recept Signal. 2008 Jun 27;6:e008
references.pmid: 18612376
references.citation: Endocrine. 2007 Aug;32(1):96-106
references.pmid: 17955388
references.citation: Endocrinology. 1996 Sep;137(9):3877-83
references.pmid: 8756560
references.citation: Am J Anat. 1990 May;188(1):3-20
references.pmid: 2161173
references.citation: Biol Reprod. 1996 Oct;55(4):895-901
references.pmid: 8879506
references.citation: Endocr Rev. 2001 Dec;22(6):764-86
references.pmid: 11739331
references.citation: Hum Mol Genet. 2002 Sep 1;11(18):2103-11
references.pmid: 12189162
references.citation: Endocrinology. 2000 Jan;141(1):37-49
references.pmid: 10614621
references.citation: Endocrinology. 2008 Jul;149(7):3279-85
references.pmid: 18403489
references.citation: Int J Androl. 2008 Sep;31(5):462-70
references.pmid: 18637153
references.citation: Endocr Rev. 1994 Feb;15(1):102-15
references.pmid: 8156935
references.citation: Acta Endocrinol (Copenh). 1990 Oct;123(4):416-22
references.pmid: 2173324
references.citation: Genesis. 2002 Jul;33(3):114-8
references.pmid: 12124943
references.citation: Mol Endocrinol. 2001 Jan;15(1):172-83
references.pmid: 11145748
references.citation: J Androl. 1998 May-Jun;19(3):335-40; discussion 341-2
references.pmid: 9639050
references.citation: Biol Reprod. 1975 Jun;12(5):609-17
references.pmid: 1220829
references.citation: J Steroid Biochem Mol Biol. 2006 Feb;98(2-3):164-73
references.pmid: 16388947
references.citation: Nat Genet. 1997 Feb;15(2):201-4
references.pmid: 9020850
references.citation: J Androl. 1992 Mar-Apr;13(2):172-84
references.pmid: 1317835
references.citation: Endocrinology. 1997 Jan;138(1):41-8
references.pmid: 8977383
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):18975-80
references.pmid: 17142319
references.citation: Science. 1995 Jun 16;268(5217):1609-12
references.pmid: 7777858
references.citation: Int J Androl. 2003 Feb;26(1):16-20
references.pmid: 12534933
references.citation: Endocrinology. 2001 Jun;142(6):2405-8
references.pmid: 11356688
references.citation: Dev Biol. 1996 Nov 1;179(2):471-84
references.pmid: 8903361
references.citation: Mol Endocrinol. 2001 Oct;15(10):1803-16
references.pmid: 11579212
references.citation: Endocr Rev. 2001 Jun;22(3):289-318
references.pmid: 11399746
references.citation: J Steroid Biochem Mol Biol. 1999 Jan;68(1-2):1-9
references.pmid: 10215032
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4961-6
references.pmid: 17360365
references.citation: Mol Cell Endocrinol. 1977 Dec;9(2):159-67
references.pmid: 598614
references.citation: J Reprod Fertil. 1986 Jan;76(1):257-66
references.pmid: 3080592
references.citation: Curr Top Dev Biol. 2003;56:25-53
references.pmid: 14584725
references.citation: Baillieres Clin Endocrinol Metab. 1992 Apr;6(2):313-33
references.pmid: 1616447
references.citation: Nature. 1975 Dec 18;258(5536):620-2
references.pmid: 1207739
references.citation: Transgenic Res. 1998 Mar;7(2):105-12
references.pmid: 9608738
references.citation: Am J Pathol. 2006 Jan;168(1):195-204
references.pmid: 16400023
references.citation: Mol Cell Endocrinol. 1999 May 25;151(1-2):205-12
references.pmid: 10411335
references.citation: Cell. 2005 Feb 11;120(3):369-82
references.pmid: 15707895
references.citation: J Endocrinol. 2006 Sep;190(3):759-70
references.pmid: 17003277
references.citation: Physiol Rev. 1971 Jan;51(1):1-22
references.pmid: 4926414
references.citation: Chem Rev. 2005 Sep;105(9):3352-70
references.pmid: 16159155
references.citation: Int J Androl. 2008 Sep;31(5):477-82
references.pmid: 17916185
references.citation: Andrologia. 2000 Jan;32(1):42-5
references.pmid: 10702865
references.citation: J Clin Endocrinol Metab. 2007 Sep;92(9):3604-10
references.pmid: 17579205
references.citation: Int J Androl. 2010 Jun 1;33(3):507-17
references.pmid: 19392831
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16696-700
references.pmid: 16275920
references.citation: Genesis. 2000 Feb;26(2):99-109
references.pmid: 10686599