title: Diverse roles for sex hormone-binding globulin in reproduction.
abstract: Sex hormone-binding globulin (SHBG) transports androgens and estrogens in blood and regulates their access to target tissues. Hepatic production of SHBG fluctuates throughout the life cycle and is influenced primarily by metabolic and hormonal factors. Genetic differences also contribute to interindividual variations in plasma SHBG levels. In addition to controlling the plasma distribution, metabolic clearance, and bioavailability of sex steroids, SHBG accumulates in the extravascular compartments of some tissues and in the cytoplasm of specific epithelial cells, where it exerts novel effects on androgen and estrogen action. In mammals, the gene-encoding SHBG is expressed primarily in the liver but also at low levels in other tissues, including the testis. In subprimate species, Shbg expression in Sertoli cells is under the control of follicle-stimulating hormone and produces the androgen-binding protein that influences androgen actions in the seminiferous tubules and epididymis. In humans, the SHBG gene is not expressed in Sertoli cells, but its expression in germ cells produces an SHBG isoform that accumulates in the acrosome. In fish, Shbg is produced by the liver but has a unique function in the gill as a portal for natural steroids and xenobiotics, including synthetic steroids. However, salmon have retained a second, poorly conserved Shbg gene that is expressed only in ovary, muscle, and gill and that likely exerts specialized functions in these tissues. The present review compares the production and functions of SHBG in different species and its diverse effects on reproduction.
authors: Child & Family Research Institute and Department of Obstetrics & Gynecology, University of British Columbia, Vancouver, British Columbia, Canada. ghammond@cw.bc.ca
authors: Geoffrey L
authors: GL
authors: Hammond
references: J Steroid Biochem. 1978 Aug;9(8):791-4
references: 568696
references: Biochemistry. 1994 Sep 6;33(35):10622-9
references: 8075062
references: Mol Endocrinol. 2011 Feb;25(2):269-81
references: 21193555
references: Endocr Rev. 2009 Dec;30(7):883-925
references: 19887492
references: J Biol Chem. 1991 Jan 5;266(1):143-54
references: 1702422
references: J Clin Endocrinol Metab. 2005 May;90(5):2618-23
references: 15687322
references: EMBO J. 2000 Feb 15;19(4):504-12
references: 10675319
references: J Mol Endocrinol. 2009 Jul;43(1):19-27
references: 19336534
references: Clin Endocrinol (Oxf). 1986 May;24(5):571-6
references: 3791651
references: Nat Clin Pract Endocrinol Metab. 2007 May;3(5):414-21
references: 17452968
references: Science. 1978 Apr 7;200(4337):65-6
references: 635573
references: J Clin Invest. 2002 Apr;109(7):973-81
references: 11927624
references: Endocrinology. 1990 Dec;127(6):3124-30
references: 1701136
references: Trends Biochem Sci. 2001 Jun;26(6):363-8
references: 11406409
references: J Biol Chem. 2002 Jul 19;277(29):26618-22
references: 12015315
references: Clin Endocrinol (Oxf). 1974 Jan;3(1):69-96
references: 4134992
references: J Clin Endocrinol Metab. 2006 Dec;91(12):5029-37
references: 16926255
references: Obstet Gynecol Clin North Am. 2002 Sep;29(3):411-23
references: 12353665
references: Monogr Endocrinol. 1986;27:1-603
references: 2421156
references: Endocrine. 2006 Oct;30(2):185-90
references: 17322577
references: J Steroid Biochem. 1989 Feb;32(2):327-34
references: 2646476
references: J Clin Endocrinol Metab. 1990 Nov;71(5):1147-50
references: 2229277
references: J Biol Chem. 2000 Aug 25;275(34):25920-5
references: 10859323
references: J Endocrinol. 2002 Oct;175(1):121-7
references: 12379496
references: J Clin Endocrinol Metab. 1986 Aug;63(2):510-2
references: 3722336
references: J Clin Endocrinol Metab. 1981 Jul;53(1):58-68
references: 7195404
references: Endocrinology. 2008 Sep;149(9):4269-75
references: 18483148
references: Curr Drug Metab. 2009 Jun;10(5):508-19
references: 19689247
references: Mol Cell Endocrinol. 2010 Mar 5;316(1):53-9
references: 19786070
references: Nat Neurosci. 2006 Feb;9(2):220-6
references: 16388309
references: J Steroid Biochem Mol Biol. 1992 Oct;43(5):423-9
references: 1327074
references: Endocrinology. 2009 Jan;150(1):366-75
references: 18703621
references: Baillieres Clin Obstet Gynaecol. 1990 Sep;4(3):419-39
references: 2282736
references: FEBS Lett. 1997 May 26;408(3):306-10
references: 9188782
references: J Clin Endocrinol Metab. 1988 Aug;67(2):234-7
references: 3392161
references: J Androl. 1998 Jan-Feb;19(1):81-91
references: 9537295
references: J Biol Chem. 2001 Sep 28;276(39):36383-90
references: 11473114
references: Mol Endocrinol. 2006 Nov;20(11):2613-29
references: 16543404
references: Maturitas. 2006 Jul 20;54(4):363-71
references: 16725287
references: Mol Cell Endocrinol. 2005 Jan 14;229(1-2):21-9
references: 15607525
references: Gen Comp Endocrinol. 2005 Feb;140(3):164-75
references: 15639144
references: Horm Res. 1999;51(5):238-41
references: 10559668
references: FASEB J. 1992 Apr;6(7):2477-81
references: 1532944
references: Biol Reprod. 1997 Jan;56(1):14-20
references: 9002628
references: Endocrinology. 1981 Mar;108(3):925-31
references: 7007029
references: Mol Cell Endocrinol. 2007 Sep 30;276(1-2):55-62
references: 17719171
references: Hum Mol Genet. 2009 Oct 1;18(19):3749-57
references: 19574343
references: Mol Endocrinol. 2004 Aug;18(8):1975-87
references: 15155787
references: Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1999 Jul;123(3):233-9
references: 10530895
references: J Clin Invest. 1976 Nov;58(5):1061-8
references: 825531
references: Pediatrics. 2008 Feb;121 Suppl 3:S208-17
references: 18245513
references: Cancer Epidemiol Biomarkers Prev. 2005 May;14(5):1096-101
references: 15894658
references: Physiol Res. 2008;57 Suppl 1:S91-S98
references: 18271688
references: J Biol Chem. 2006 Jun 9;281(23):15853-61
references: 16601122
references: Biol Reprod. 1980 Feb;22(1):9-17
references: 6991014
references: J Androl. 1998 Sep-Oct;19(5):527-41
references: 9796612
references: Toxicol Appl Pharmacol. 2009 Jan 1;234(1):47-57
references: 18725242
references: N Engl J Med. 2001 Sep 27;345(13):971-80
references: 11575290
references: Biol Reprod. 2002 Apr;66(4):877-85
references: 11906904
references: J Clin Endocrinol Metab. 1998 Jan;83(1):235-40
references: 9435448
references: J Biol Chem. 2002 Nov 22;277(47):45219-25
references: 12228253
references: J Clin Endocrinol Metab. 2005 Nov;90(11):6275-82
references: 16131577
references: Mol Endocrinol. 1998 Jan;12(1):123-36
references: 9440816
references: Biol Chem. 2000 Mar;381(3):199-209
references: 10782991
references: Int J Androl. 1985 Feb;8(1):21-7
references: 3922901
references: Science. 1981 Mar 20;211(4488):1285-94
references: 7010603
references: Endocr Rev. 2003 Jun;24(3):313-40
references: 12788802
references: Proc Natl Acad Sci U S A. 1987 Jan;84(2):339-43
references: 2432609
references: Mol Endocrinol. 1988 Jan;2(1):3-13
references: 2840566
references: Fertil Steril. 1984 Jul;42(1):44-51
references: 6233179
references: J Clin Endocrinol Metab. 2009 Dec;94(12):4793-800
references: 19850695
references: Mol Cell Endocrinol. 2010 Mar 5;316(1):60-5
references: 19733622
references: Climacteric. 2008;11 Suppl 1:41-6
references: 18464022
references: J Clin Invest. 2007 Dec;117(12):3979-87
references: 17992261
references: Toxicol Lett. 1998 Dec 28;102-103:337-42
references: 10022275
references: N Engl J Med. 2009 Sep 17;361(12):1152-63
references: 19657112
references: J Mol Biol. 2002 May 3;318(3):621-6
references: 12054810
references: Vitam Horm. 2011;85:149-84
references: 21353880
references: J Steroid Biochem Mol Biol. 1999 Apr-Jun;69(1-6):481-5
references: 10419028
references: J Biol Chem. 1998 Dec 18;273(51):34105-14
references: 9852068
references: Biol Reprod. 1998 Feb;58(2):520-5
references: 9475409
references: Horm Behav. 2010 Apr;57(4-5):434-40
references: 20109458
references: Vitam Horm. 1994;49:197-280
references: 7810071
references: J Biol Chem. 2005 Feb 11;280(6):4462-8
references: 15574421
references: Horm Res. 1996;45(3-5):197-201
references: 8964583
references: J Clin Endocrinol Metab. 2005 Jul;90(7):3847-53
references: 15827095
references: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12865-70
references: 12297623
references: J Clin Endocrinol Metab. 1992 Oct;75(4):1066-70
references: 1400872
references: Mol Endocrinol. 1989 Nov;3(11):1869-76
references: 2608061
references: Baillieres Clin Endocrinol Metab. 1989 Nov;3(3):723-53
references: 2698153
references: Clin Endocrinol (Oxf). 1983 Apr;18(4):377-84
references: 6683603
references: Trends Genet. 2008 Jan;24(1):41-7
references: 18063438
references: Cell. 2005 Sep 9;122(5):751-62
references: 16143106
references: Endocrinology. 2004 Nov;145(11):5221-30
references: 15284198
references: Endocrinology. 2008 Jun;149(6):2980-9
references: 18339711
references: Fertil Steril. 1998 Feb;69(2):324-8
references: 9496349
references: Endocrinology. 1999 Sep;140(9):4166-74
references: 10465289
references: J Neuroendocrinol. 2009 Mar;21(4):421-6
references: 19207815
references: Mol Cell Endocrinol. 2010 Mar 5;316(1):13-23
references: 19748550
references: Horm Metab Res. 2006 Apr;38(4):230-5
references: 16700003
references: Endocrinology. 2008 May;149(5):2333-40
references: 18202134
references: Endocrinology. 2010 Nov;151(11):5165-73
references: 20843997
references: J Biol Chem. 2002 Nov 22;277(47):45291-8
references: 12235141
references: Steroids. 1996 Jul;61(7):392-400
references: 8837290
references: Endocrinology. 2005 Apr;146(4):1965-72
references: 15625245
references: Reproduction. 2010 Sep;140(3):399-410
references: 20802107
references: Endocrinology. 1994 Mar;134(3):1515-27
references: 8119194
references: Am J Physiol Endocrinol Metab. 2010 Nov;299(5):E741-51
references: 20682841
references: BMC Mol Biol. 2009 Jun 17;10:59
references: 19534810
references: J Biol Chem. 2002 Aug 30;277(35):32086-93
references: 12065592
references: Treat Endocrinol. 2002;1(6):372-86
references: 15832490
references: Endocrinology. 2010 Feb;151(2):595-605
references: 19966179
references: Endocrinology. 2009 May;150(5):2183-9
references: 19179433
references: Biochem J. 2006 Jul 1;397(1):159-68
references: 16584384