Sex hormone regulation (SHBG)

Sex hormone-binding globulin is a steroid-binding protein that is affected by various factors such as age and can serve as an indicator of endocrine disorders or metabolic diseases.

The female sex hormones are estrogen and progesterone, whose main functions are the development and maintenance of female sexual characteristics, as well as participating in the development of the menstrual cycle, fertility, preparation of the reproductive system for the reception of sperm and gestation. The most important estrogen synthesized by the ovary is estradiol, while progesterone is the most important hormone of the gestagens or pregnancy hormones.

Sex hormone binding globulin (SHBG), produced by the liver, is a circulating steroid transport protein. It is produced by hepatocytes and binds to biologically active androgens and estrogens, thereby regulating their plasma levels and bioavailability.

In addition to controlling plasma distribution, intrinsic metabolic clearance (the ability of hepatocytes to eliminate a substance without influence from the bloodstream) and bioavailability, it also controls the metabolic intrinsic clearance (the ability of hepatocytes to eliminate a substance without influence from the bloodstream) and bioavailability.neo) and the bioavailability of sex steroids, SHBG accumulates in the extravascular compartments of some tissues and in the cytoplasm of specific epithelial cells, where it exerts further effects on the action of androgens and estrogens.

Since the liver is the central metabolic organ in which it is produced, certain metabolic diseases cause changes in serum SHBG levels. SHBG levels can also vary due to endocrine disorders, thus SHBG stands as one of the mediators between various endocrine tissues and definitely contributes its own pathophysiological role in diseases such as: obesity, metabolic syndrome, polycystic ovary syndrome, osteoporosis, breast and prostate cancer.

It is estimated that approximately 50% of the variation in SHBG concentrations in the bloodstream is inherited from the parents, suggesting that SHBG levels are under significant genetic control.

Number of observed variants

13.5 million variants

Number of loci analyzed

553 loci

Genes analyzed

AADAT ABCA1 ABCA6 ABCA8 ABCB6 ABCC6 ABCC8 ABI3BP ABO ACTG1 ACTRT3 ADAM9 ADAR ADCY5 ADGRD1 ADGRV1 ADH4 AES AKNA AKR1C4 AKT1 ALG13 AMD1 ANKS1B ANO3 ANXA9 APOC1 APOC1P1 APOH APOL6 ARFGEF2 ARHGAP10 ARHGAP22 ARHGEF19 ARHGEF28 ARHGEF39 ARID2 ARID4B ARID5B ARL15 ARL6IP5 ARMC2 ARNTL ARSE AS3MT ASB9 ATF1 ATF7 ATG4C ATP5D ATPAF2 AUH AUTS2 BANP BCAS3 BCKDHB BCL2 BCL2L11 BCORL1 BEND3 BICD2 BICDL1 BLMH BMF BMP7 BMP8A BORCS7-ASMT BRD3 BRI3 BRWD1 C10orf11 C11orf80 C15orf54 C22orf24 C2orf42 C4orf45 C5orf56 C5orf67 CACNA2D1 CAND1 CARS CARS2 CASC21 CASC8 CATSPER2P1 CBLB CBX6 CBX8 CCDC107 CCDC153 CCDC157 CCDC66 CCDC77 CCND2 CCND2-AS1 CCT2 CD163 CD276 CD34 CDK6 CDK8 CDKAL1 CDKN1A CDKN2B-AS1 CDRT15P1 CEACAM16 CEP120 CEP68 CFAP61 CFL2 CHCHD7 CHD2 CHEK2 CIC CLDN25 CLEC16A CMIP CNOT4 COBLL1 COL15A1 COL4A2 COLEC11 COQ8A COX19 CPEB4 CPS1 CREB1 CRY2 CSF3 CSRNP1 CTDSP1 CTSS CUX1 CUX2 CXCR5 CXorf56 CYB5A CYFIP2 CYHR1 CYP19A1 CYP26A1 CYP7A1 D DANT2 DCAF6 DCBLD2 DDB2 DGCR8 DGKD DGKQ DHX35 DICER1 DLEU1 DLEU2 DLG5 DMRTA1 DMTN DNAJC13 DNM3 DNMT3A DOCK11 DOCK4 DPH6-AS1 DPM1 DSTYK E2F7 EBF1 EDEM3 EFL1 EGR1 ELMSAN1 EMILIN2 EML4 EML6 ENTPD1-AS1 EPB41 EPHA1 EPHX1 ERLIN1 ERN1 ETS1 EXOC4 EYA1 EYA2 FAM13A FAM47E FAM47E-STBD1 FAM76B FAM8A1 FBXW2 FCGRT FGF17 FGF9 FKBP1AP1 FKBP4 FLJ26245 FLJ41200 FMO3 FNIP1 FOSL2 FOXN2 FOXN3 FOXP1 FSTL3 FZD9 GAB1 GAB2 GATAD2A GBAS GCK GHR GLDC GLIS3 GLTSCR1 GPAM GREB1 GSTM1 GSTT2B GTF2A2 H1FX-AS1 HDGFRP2 HECTD4 HELZ HERC4 HGF HGFAC HHIP HIVEP3 HLA-B HLX HMCN2 HMGA2 HN1 HNF1A HNF1B HNF4A HNRNPD HORMAD1 HPN HPN-AS1 HPRT1 HSD17B13 ICAM4 ID4 IFITM2 IGF1 IGF2BP2 IGFALS IL17REL IL32 IMP3 INS-IGF2 INSR IP6K1 IPO11 IRF2 IRF2BP1 IRS1 ISCA1 ITCH ITFG1 ITIH1 ITPR2 JADE2 JARID2 JAZF1 JMJD1C JUND KALRN KANSL2 KAT5 KCNIP2 KCNIP2-AS1 KCNJ2 KCNT2 KCNU1 KDM6A KIAA1656 KLF12 KLF13 KLF14 KLHL24 KRAS L3MBTL3 LAG3 LARP1B LCORL LHX3 LHX9 LIN9 LINC00094 LINC00261 LINC00513 LINC00536 LINC00862 LINC00924 LINC01091 LINC01101 LINC01184 LINC01214 LINC01230 LINC01258 LINC01271 LINC01488 LINC01544 LINC01605 LINC01625 LINC02101 LOC100506127 LOC100507053 LOC100507065 LOC100507144 LOC101060091 LOC101927636 LOC101927770 LOC101928306 LOC101928728 LOC101928994 LOC101929058 LOC102723886 LOC102724084 LOC102724152 LOC102724301 LOC102724596 LOC105374960 LOC105376360 LOC105377480 LOC157273 LOC284788 LOC285889 LOC340357 LOC401324 LOC643339 LOC646736 LOC730338 LPIN3 LRP5 LSM12 M2-AS1 MAD1L1 MAFTRR MANEA MAP2K7 MAPK10 MAPKAP1 MAPRE3 MAPT MCC MCM9 MEOX2-AS MET METAP2 METTL21A MGRN1 MICAL3 MIER3 MIR17HG MIR203A MIR22HG MIR4421 MIR4435-2HG MIR4738 MIR5189 MIR5705 MIR588 MIR600HG MIR6129 MIR99AHG MLX MPDU1 MRAS MSL2 MTF2 MTOR MYEOV MYH10 MYO5A MYOZ2 MYRF NAB1 NADK2 NCEH1 NCOA2 NCOR1 NDRG4 NEAT1 NEURL3 NF1 NFE2L2 NFIA NFIB NFIC NFIX NINJ2 NKX2-6 NPEPPS NPPA-AS1 NR1D1 NR1H4 NR2F2-AS1 NR2F6 NR3C1 NRBF2 NSL1 NT5C1B-RDH14 NUDCD2 NUDT3 NWD2 NYNRIN OASL OIT3 ONECUT1 ONECUT2 OPTC ORC4 OSGIN1 OSMR-AS1 OVOL1 PACRG-AS1 PALM3 PAM PAPPA PARP15 PDE3A PDGFC PDXDC1 PEPD PHF8 PIK3R1 PIM3 PKN3 PLA2G12A PLCE1 PLEC PNPLA3 POLG2 PPARA PPARG PPARGC1A PPP4R3A PRKAA2 PRKAG3 PRMT6 PRMT7 PRODH PROX1 PROX1-AS1 PTEN PTGES3 PTMS PTPRF PUM1 PXK PXMP4 PYY2 QSER1 R3HDM2 RAB24 RAB29 RABEP1 RAPGEF4 RASA3 REPS1 RGS6 RHOBTB2 RIC1 RIT1 RMI1 RNASEH2C RNF212B RNU6ATAC RORA RPS6KA3 RPSAP52 RREB1 RSBN1L RSF1 RXRA SALL1 SBNO2 SCAF4 SCAP SDC1 SEPHS1 SERPINA1 SERTAD2 SETD9 SGK1 SGPP2 SHBG SLC17A3 SLC20A2 SLC22A3 SLC25A37 SLC30A8 SLC38A4 SLC45A3 SLC7A10 SLCO1B1 SMAD7 SMARCA2 SMCHD1 SMCO1 SMOX SMYD2 SNX10 SNX13 SNX17 SNX5 SOCS2 SOS1 SOS2 SOX5 SOX6 SP1 SP100 SPATA20 SPDL1 SPPL2A SRD5A3-AS1 SRPX SRRT SSBP3 SSU72 STC2 STN1 STX3 SULT1E1 SV2A SVEP1 SYAP1 TADA1 TAT TBL1X TCEA3 TCF15 TDGF1P3 TERT TEX22 TFEB TGDS THEM4 THOC2 THOP1 THRB TJP3 TKTL1 TLE1 TMEM163 TMEM176A TMEM176B TMEM212 TMEM243 TMEM57 TMOD1 TNFSF10 TNKS2 TNP1 TNPO1 TRAM2 TRH TRIM2 TRIM49B TRIM5 TRIM69 TRIOBP TSEN15 TSPAN8 TTL TUSC8 TXN TXNDC11 UBASH3B UBE2D3 UBE2K UBE2L3 UBE4B UBN1 UGT1A10 UGT1A6 UGT1A7 UGT1A8 UGT1A9 UGT2B15 UGT2B17 UHRF2 UPF3A USE1 USP15 USP3 USP34 USP43 USP51 VEGFA VGLL2 VGLL3 VPS13C WARS WDR11 WDR41 WDR72 WDR78 WDR81 WNT2B XRN1 YAP1 YIPF4 ZBTB10 ZBTB2 ZBTB41 ZBTB45 ZC3HC1 ZCCHC2 ZEB1-AS1 ZFPM1 ZFX-AS1 ZFYVE21 ZGPAT ZMIZ1 ZMIZ2 ZMYM4 ZMYND8 ZNF217 ZNF316 ZNF385B ZNF423 ZNF573 ZNF638 ZNF644 ZNF664 ZNF664-RFLNA ZNF678 ZNF770 ZNF787 ZNF799 ZNF845 ZSCAN25 ZWILCH

Bibliography

Ruth K.S., Day F.R., et al. Using human genetics to understand the disease impacts of testosterone in men and women. Nature Medicine, 10 Feb 2020, 26(2):252-258

Hammond G.L. Diverse Roles for Sex Hormone-Binding Globulin in Reproduction. Biol Reprod. 2011 Sep; 85(3): 431–441.

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