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. Author manuscript; available in PMC: 2016 Aug 15.
Published in final edited form as: Biol Psychiatry. 2015 Jan 14;78(4):259–269. doi: 10.1016/j.biopsych.2014.12.024

Table 1.

Significantly enriched KEGG pathways for genes uniquely regulated by testosterone replacement, estradiol replacement, or commonly regulated by both treatments.
Term Fold Enrichment Gene Count Genes Fisher Exact p-Value
Commonly Regulated Cytokine-cytokine receptor interaction 2.5322 34 Loc678883, Csf2, Rgd1561292, Rgd1565911, Il9r, Il6st, Ctf1, Tnfsf14, Kitlg, Il13, Il11, Lif, Rgd1565225, Il12rb1, Cxcr5, Loc691874, Csf2rb, Epo, Il4, Il3, Flt3, Rgd1559932, Tnfrsf13c, Tnfrsf14, Edar, Osm, Ccr8, Loc500598, Ccr6, Tnfsf13b, Il20ra, Cd40lg, Cxcl13, Ccr4, Ifna11, Loc678867, Il12b, Ngfr <0.00001
Neuroactive ligand-receptor interaction 1.9040 34 Cckar, Taar7e, Grik2, Drd4, F2rl1, Ppyr1, Bdkrb1, Adrb3, Ptgir, Hrh1, P2ry4, Ltb4r, S1pr4, Galr2, Mcpt8l2, Mc5r, Mc3r, Taar4, Taar3, Gpr156, Ptger4, Gabra3, Ptgdrl, Npbwr1, Htr4, Mcpt8, Ntsr1, Sstr5, Gpr35, Rgd1565970, Ltb4r2, Ptgdr, Gpr50, Uts2r, Tshr, Glp1r, Ctsg 0.0002
MAPK signaling pathway 1.5444 28 Fgfr2, Fgf6, Fgf5, Fgf8, Fgf17, Rgd1561394, Map4k1, Hspa1a, Hspa1b, Casp3, Rasgrp3, Map3k2, Pla2g12b, Dusp16, Sos2, Pla2g1b, Fgf1, Traf6, Fgf3, Ntf4, Pla2g10, Chp2, Raf1, Cacng1, Cacna2d2, Cacna2d4, Hspb1, Pla2g2d, Pla2g2f 0.0130
Jak-STAT signaling pathway 2.5333 24 Csf2, Rgd1561292, Rgd1565911, Il9r, Loc685840, Il6st, Loc687396, Ctf1, Il13, Il11, Lif, Il12rb1, Rgd1565225, Sos2, Csf2rb, Epo, Il4, Il3, Socs2, Rgd1559932, Il24, Osm, Cblc, Il20ra, Ifna11, Il12b 0.0000
Regulation of actin cytoskeleton 1.6848 24 Fgfr2, Fgf6, Myl7, Fgf5, Fgf8, Arhgef7, Limk1, Arhgef6, Diaph2, Fgf17, Abi2, Itga10, Raf1, Bdkrb1, Iqgap1, Vcl, Itgb7, Sos2, Itgad, Mylc2pl, Ins2, Fgf1, Pip4k2c, Fgf3 0.0077
Cell adhesion molecules (CAMs) 1.9827 20 Cldn7, Selp, Cldn18, Mpz, Cldn4, Cldn6, Rt1-M2, Cdh1, Rt1-Ec2, Rt1-Da, Pdcd1, Pdcd1lg2, Cldn23, Sdc3, Cd40lg, Itgb7, Rt1-T18, Cd2, Cd22, Spn 0.0023
Vascular smooth muscle contraction 2.0774 16 Pla2g10, Prkch, Raf1, Prkcd, Kcnmb1, Itpr1, Ptgir, Plcb4, Gnaq, Calml3, Pla2g12b, Pla2g1b, Calm4, Plcb1, Pla2g2d, Pla2g2f 0.0039
Tight junction 1.8058 16 Myl7, Cldn7, Cldn18, Cldn4, Cldn6, Myh3, Rgd1561394, Prkci, Prkch, Prkcd, Cldn23, Tjp1, Ash1l, Exoc4, Mylc2pl, Myh7b 0.0150
GnRH signaling pathway 2.3413 15 Pla2g10, Raf1, Prkcd, Itpr1, Plcb4, Gnaq, Map3k2, Calml3, Pla2g12b, Sos2, Pla2g1b, Calm4, Plcb1, Pla2g2d, Pla2g2f 0.0016
Hematopoietic cell lineage 2.6334 14 Il4, Il3, Csf2, Il9r, Flt3, Fcer2, Kitlg, Rt1-Da, Il11, Cd19, Tfrc, Cd2, Cd22, Epo 0.0007
Melanogenesis 2.2327 14 Kitlg, Lef1, Raf1, Fzd7, Loc679869, Plcb4, Gnaq, Loc683733, Calml3, Calm4, Creb3l4, Wnt9a, Wnt6, Plcb1, Wnt8a 0.0035
Long-term depression 2.6278 12 Plcb4, Gnaq, Pla2g10, Pla2g12b, Pla2g1b, Raf1, Prkg2, Plcb1, Gsbs, Pla2g2d, Itpr1, Pla2g2f 0.0016
Fc epsilon RI signaling pathway 2.3166 12 Il4, Il3, Csf2, Pla2g10, Sos2, Pla2g12b, Pla2g1b, Raf1, Il13, Prkcd, Pla2g2d, Pla2g2f 0.0049
Autoimmune thyroid disease 2.6458 11 Il4, Prf1, Rgd1565911, Rgd1565225, Cd40lg, Rgd1559932, Rt1-T18, Rt1-M2, Ifna11, Rt1-Ec2, Tshr, Rt1-Da 0.0024
Glycerophospholipid metabolism 2.3664 10 Pla2g10, Dgkg, Pla2g12b, Pla2g1b, Pemt, Lycat, Pcyt1b, Pla2g2d, Chat, Pla2g2f 0.0085
VEGF signaling pathway 1.9827 10 Sh2d2a, Ptgs2, Pla2g10, Pla2g12b, Pla2g1b, Chp2, Raf1, Hspb1, Pla2g2d, Pla2g2f 0.0270
B cell receptor signaling pathway 1.9563 10 Loc688112, Bcl10, Loc690948, Chp2, Raf1, Loc687079, Loc683446, Pira2, Lilrb3l, Cd19, Rasgrp3, Lilrb3, Sos2, Cd22, Cd79b, Cd79a, Ddah1 0.0300
Gap junction 1.8113 10 Tjp1, Plcb4, Loc679312, Gnaq, Map3k2, Sos2, Raf1, Prkg2, Plcb1, Itpr1 0.0470
Melanoma 1.9137 9 Fgf6, Fgf5, Fgf8, Cdkn2a, Fgf17, Raf1, Cdh1, Fgf1, Fgf3 0.0430
Maturity onset diabetes of the young 4.5144 8 Onecut1, Gck, Hnf4a, Foxa2, Bhlha15, Pdx1, Neurog3, Ins2 0.0002
Steroid hormone biosynthesis 2.7297 8 Hsd17b2, Cyp11a1, Cyp11b1, Cyp11b2, Cyp21a1, Ugt1a1, Ugt1a6, Ugt1a9, Cyp17a1, Ugt1a8, Ugt1a7c, Ugt1a3, Ugt1a2, Ugt1a5, Ugt2a1 0.0076
Allograft rejection 2.2146 8 Il4, Prf1, Cd40lg, Rt1-T18, Rt1-M2, Il12b, Rt1-Ec2, Rt1-Da 0.0260
Arginine and proline metabolism 2.2146 8 Pycr1, Abp1, Ckm, Prodh2, Dao, Aldh1a7, Agmat, Aldh3a2 0.0260
Glycerolipid metabolism 2.3342 7 Cel, Dgkg, Lipg, Lycat, Aldh1a7, Lipc, Aldh3a2 0.0280
Asthma 3.8275 6 Il4, Il3, Cd40lg, Prg2, Il13, Rt1-Da 0.0036
Primary immunodeficiency 2.5892 6 Cd19, Cd40lg, Tnfrsf13c, Aire, Rag1, Cd79a, Loc687079 0.0250
Ether lipid metabolism 2.5892 6 Pla2g10, Pla2g12b, Pla2g1b, Lycat, Pla2g2d, Pla2g2f 0.0250
alpha-Linolenic acid metabolism 4.3153 5 Pla2g10, Pla2g12b, Pla2g1b, Pla2g2d, Pla2g2f 0.0045
Histidine metabolism 3.0566 5 Abp1, Ftcd, Aldh1a7, Uroc1, Aldh3a2 0.0210
Testosterone Only Pathways in cancer 1.4751 22 Wnt5a, Fgf14, Wnt1, Max, Ptk2, Stat4, Lamb2, Sos1, Pik3ca, Egf, Pik3r1, Loc685653, Loc685590, Bmp4, Loc499735, Crebbp, Rxrg, Hgf, Stat1, Rad51, Fzd6, Wnt2b, Cdkn1a, Ncoa4, Loc685605, Crk, Loc685626 0.0420
Neuroactive ligand-receptor interaction 1.7036 21 Rgd1308470, Tspo, Drd3, Tacr2, Gabrb2, Npy2r, Bdkrb2, Gabbr2, Gcgr, Grid2, Mcpt8l2, Mcpt8l3, C5ar1, Pth2r, Gabra4, Gzma, Gabra6, Mcpt8, Mcpt10, Crhr2, Prlr, Chrm3, Rgd1565970, Drd1a, Glp1r 0.0110
Focal adhesion 1.6350 15 Rgd1563410, Loc295810, Itga1, Mylk2, Hgf, Itga4, Vav2, Actg1, Ptk2, Lamb2, Sos1, Pik3ca, Loc680688, Egf, Loc685605, Crk, Rapgef1, Loc685653, Loc685626, Pik3r1, Loc685590, Thbs4 0.0400
Insulin signaling pathway 2.0933 13 Socs3, Phkb, Phka1, Fbp1, Mknk2, Eif4ebp1, Hk3, Sos1, Pik3ca, Prkaa1, Loc685605, Crk, Rapgef1, Pik3r1, Loc685626, Loc685653, Loc685590 0.0088
ErbB signaling pathway 2.7506 11 Nrg3, Erbb4, Ptk2, Cdkn1a, Eif4ebp1, Sos1, Camk2d, Pik3ca, Loc685605, Egf, Crk, Pik3r1, Loc685626, Loc685653, Loc685590 0.0019
TGF-beta signaling pathway 2.2243 9 Bmp4, Rgd1309707, Loc684620, Loc679119, Loc690504, Gdf6, Rbl1, Smad5, Crebbp, Bmp7, Thbs4 0.0190
Progesterone-mediated oocyte maturation 2.1988 9 Anapc1, Loc499735, Cpeb1, Cdc25c, Rps6ka6, Mapk13, Pik3ca, Anapc7, Loc685605, Pik3r1, Loc685626, Loc685653, Loc685590 0.0200
Inositol phosphate metabolism 3.2700 8 Pip5k3, Aldh6a1, Plce1, Pik3c2a, Synj1, Pik3c3, Pik3ca, Ocrl, Loc685605, Loc685653, Loc685626, Loc685590 0.0027
Phosphatidylinositol signaling system 2.4291 8 Pip5k3, Plce1, Pik3c2a, Synj1, Pik3c3, Pik3ca, Ocrl, Loc685605, Loc685653, Loc685626, Pik3r1, Loc685590 0.0160
Hematopoietic cell lineage 2.1800 8 Il1r1, Dntt, Cd3e, Rt1-Db1, Fcer2, Itga1, Mme, Itga4 0.0290
Retinol metabolism 2.5218 7 Cyp1a2, Ugt1a1, Rdh5, Rdh12, Ugt1a6, Cyp4x1, Ugt1a9, Rdh7, Ugt1a8, Ugt1a7c, Ugt1a3, Ugt1a2, Ugt1a5, Cyp4a8, Retsat 0.0200
Sphingolipid metabolism 3.0364 6 Sgpl1, Pomt2, Sptlc2, Acer1, Galc, Sgms1, Asah2 0.0130
Intestinal immune network for IgA production 2.8340 6 Rt1-Db1, Madcam1, Itga4, Pigr, Il10, Loc688090, Rt1-Bb 0.0180
Hedgehog signaling pathway 2.4525 6 Bmp4, Wnt5a, Wnt1, Loc679119, Bmp7, Wnt2b 0.0340
Renin-angiotensin system 5.3137 5 Ren, Rgd1565970, Mcpt8l2, Mme, Mcpt8l3, Cma1, Mcpt8, Mcpt10 0.0019
Taurine and hypotaurine metabolism 6.3764 3 Gad2, Baat, Gad1 0.0097
Estradiol Only Neuroactive ligand-receptor interaction 1.8553 16 Taar7a, Taar8c, Prss1, Oxtr, Lpar2, Nr3c1, Ptgfr, Gh1, Taar9, Nmur1, Galr3, Avpr1b, F2, Glp2r, Htr2c, Htr1f 0.0120
Endocytosis 1.9649 13 Rgd1309707, Loc684620, Rt1-M4, Dnm3, Il2rb, Ret, Loc690504, Cbl, Rufy1, Rgd1561176, Zfyve20, Chmp2b, Rab22a, Rab11b, Smurf2, Pdcd6ip 0.0150
Jak-STAT signaling pathway 2.6228 12 Il2rb, Il23r, Il5, Cbl, Stat1, Ptpn11, Il20, Gh1, Ifna2, Stat4, Ifna1, Rgd1565225, Il20rb, Ccnd2, Ifna11 0.0020
Calcium signaling pathway 1.8362 11 Loc497963, Slc8a2, Gna11, Ppp3r2, Oxtr, Sae1, Ptgfr, Avpr1b, Gnas, Cacna1e, Cacna1f, Nos2, Loc678722, Htr2c 0.0370
Ubiquitin mediated proteolysis 2.1700 9 Loc691436, Rgd1309707, Loc684620, Loc690504, Ube2z, Slc8a2, Loc499959, Cbl, Sae1, Ube2c, Cul5, Wwp2, Smurf2, Loc678722, Ube2s 0.0220
Insulin signaling pathway 2.0714 9 Ppp1r3c, G6pc, Ppp1r3b, Sorbs1, Pklr, Cbl, Acaca, Pde3b, Ins1 0.0290
Retinol metabolism 4.1194 8 Rdh8, Cyp4a2, Cyp4a3, Adh1, Cyp2c7, Cyp2c23, Dhrs9, Adh7, Cyp2a1 0.0006
Natural killer cell mediated cytotoxicity 2.4304 8 Ifna2, Ifna1, Rgd1565225, Tnfrsf10b, Ifna11, Ppp3r2, Gzmb, Nfatc3, Hcst, Ptpn11 0.0170
Autoimmune thyroid disease 3.4863 7 Tg, Rt1-M4, Ifna2, Ifna1, Rgd1565225, Il5, Rt1-Ha, Ifna11, Gzmb 0.0036
Drug metabolism 2.9537 7 Adh1, Aldh1a3, Cyp2c7, Cyp2c23, Adh7, Cyp2d3, Cyp2a1 0.0090
Antigen processing and presentation 2.4166 7 Rt1-M4, Ifna2, Ifna1, Rgd1565225, Cd8a, Rfx5, Rt1-Ha, Ifna11, Nfyc 0.0250
PPAR signaling pathway 2.5674 6 Plin, Cyp4a2, Sorbs1, Cyp4a3, Scd, Loc301444, Cyp8b1, Dbi 0.0290
Notch signaling pathway 3.1000 5 Dtx2-Ps1, Psen1, Rbpsuh, Dtx2, Skiip, Rbpj, Ptcra 0.0220
Tyrosine metabolism 3.5742 4 Adh1, Aldh1a3, Adh7, Aoc3 0.0240