Testosterone

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Revision as of 05:43, 30 October 2008

Testosterone Pubchem(6013) A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.

KEGG Pathway(C00535,D00075) Androgen and estrogen metabolism Prostate cancer Activity Androgen

MMDB ID: 15896 PDB ID: 1I37 Reference: Sack JS, Kish KF, Wang C, Attar RM, Kiefer SE, An Y, Wu GY, Scheffler JE, Salvati ME, Krystek SR Jr, Weinmann R, Einspahr HMCrystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosteroneProc. Natl. Acad. Sci. U. S. A. v98, p.4904-4909 The structures of the ligand-binding domains (LBD) of the wild-type androgen receptor (AR) and the T877A mutant corresponding to that in LNCaP cells, both bound to dihydrotestosterone, have been refined at 2.0 A resolution. In contrast to the homodimer seen in the retinoid-X receptor and estrogen receptor LBD structures, the AR LBD is monomeric, possibly because of the extended C terminus of AR, which lies in a groove at the dimerization interface....

MMDB ID: 15897 PDB ID: 1I38 Reference: Sack JS, Kish KF, Wang C, Attar RM, Kiefer SE, An Y, Wu GY, Scheffler JE, Salvati ME, Krystek SR Jr, Weinmann R, Einspahr HMCrystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosteroneProc. Natl. Acad. Sci. U. S. A. v98, p.4904-4909 The structures of the ligand-binding domains (LBD) of the wild-type androgen receptor (AR) and the T877A mutant corresponding to that in LNCaP cells, both bound to dihydrotestosterone, have been refined at 2.0 A resolution. In contrast to the homodimer seen in the retinoid-X receptor and estrogen receptor LBD structures, the AR LBD is monomeric, possibly because of the extended C terminus of AR, which lies in a groove at the dimerization interface....

MMDB ID: 18740 PDB ID: 1I9J Reference: Valjakka J, Takkinenz K, Teerinen T, Soderlund H, Rouvinen JStructural insights into steroid hormone binding: the crystal structure of a recombinant anti-testosterone Fab fragment in free and testosterone-bound formsJ. Biol. Chem. v277, p.4183-4190 The monoclonal anti-testosterone antibody (3-C(4)F(5)) has a relatively high affinity (3 x 10(8) m(-1)) with an overall good specificity profile. However, the earlier characterized binding properties have shown that both the affinity and specificity of this antibody must be improved if it is intended for use in clinical immunoassays....

MMDB ID: 19484 PDB ID: 1J96 Reference: Nahoum V, Gangloff A, Legrand P, Zhu DW, Cantin L, Zhorov BS, Luu-The V, Labrie F, Breton R, Lin SXStructure of the human 3alpha-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-A resolutionJ. Biol. Chem. v276, p.42091-42098 The first crystallographic structure of human type 3 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD3, AKR1C2), an enzyme playing a critical role in steroid hormone metabolism, has been determined in complex with testosterone and NADP at 1.25-A resolution. The enzyme"s 17beta-HSD activity was studied in comparison with its 3alpha-HSD activity....

MMDB ID: 30244 PDB ID: 1Q13 Reference: Couture JF, Legrand P, Cantin L, Labrie F, Luu-The V, Breton RLoop relaxation, a mechanism that explains the reduced specificity of rabbit 20alpha-hydroxysteroid dehydrogenase, a member of the aldo-keto reductase superfamilyJ. Mol. Biol. v339, p.89-102 The aldo-keto reductase rabbit 20alpha-hydroxysteroid dehydrogenase (rb20alpha-HSD; AKR1C5) is less selective than other HSDs, since it exerts its activity both on androgens (C19 steroids) and progestins (C21 steroids). In order to identify the molecular determinants responsible for this reduced selectivity, binary (NADPH) and ternary (NADP(+)/testosterone) complex structures were solved to 1.32A and 2.08A resolution, respectively....

MMDB ID: 30428 PDB ID: 1VPO Reference: Valjakka J, Hemminki A, Niemi S, Soderlund H, Takkinen K, Rouvinen JCrystal structure of an in vitro affinity- and specificity-matured anti-testosterone Fab in complex with testosterone. Improved affinity results from small structural changes within the variable domainsJ. Biol. Chem. v277, p.44021-44027 A highly selective, high affinity recombinant anti-testosterone Fab fragment has been generated by stepwise optimization of the complementarity-determining regions (CDRs) by random mutagenesis and phage display selection of a monoclonal antibody (3-C(4)F(5)). The best mutant (77 Fab) was obtained by evaluating the additivity effects of different independently selected CDR mutations....

MMDB ID: 54139 PDB ID: 2Q7I Reference: Askew EB, Gampe RT Jr, Stanley TB, Faggart JL, Wilson EMModulation of androgen receptor activation function 2 by testosterone and dihydrotestosteroneJ. Biol. Chem. v282, p.25801-25816 The androgen receptor (AR) is transcriptionally activated by high affinity binding of testosterone (T) or its 5alpha-reduced metabolite, dihydrotestosterone (DHT), a more potent androgen required for male reproductive tract development. The molecular basis for the weaker activity of T was investigated by determining T-bound ligand binding domain crystal structures of wild-type AR and a prostate cancer somatic mutant complexed with the AR FXXLF or coactivator LXXLL peptide....

MMDB ID: 54140 PDB ID: 2Q7J Reference: Askew EB, Gampe RT Jr, Stanley TB, Faggart JL, Wilson EMModulation of androgen receptor activation function 2 by testosterone and dihydrotestosteroneJ. Biol. Chem. v282, p.25801-25816 The androgen receptor (AR) is transcriptionally activated by high affinity binding of testosterone (T) or its 5alpha-reduced metabolite, dihydrotestosterone (DHT), a more potent androgen required for male reproductive tract development. The molecular basis for the weaker activity of T was investigated by determining T-bound ligand binding domain crystal structures of wild-type AR and a prostate cancer somatic mutant complexed with the AR FXXLF or coactivator LXXLL peptide....

MMDB ID: 54141 PDB ID: 2Q7K Reference: Askew EB, Gampe RT Jr, Stanley TB, Faggart JL, Wilson EMModulation of androgen receptor activation function 2 by testosterone and dihydrotestosteroneJ. Biol. Chem. v282, p.25801-25816 The androgen receptor (AR) is transcriptionally activated by high affinity binding of testosterone (T) or its 5alpha-reduced metabolite, dihydrotestosterone (DHT), a more potent androgen required for male reproductive tract development. The molecular basis for the weaker activity of T was investigated by determining T-bound ligand binding domain crystal structures of wild-type AR and a prostate cancer somatic mutant complexed with the AR FXXLF or coactivator LXXLL peptide....

MMDB ID: 54142 PDB ID: 2Q7L Reference: Askew EB, Gampe RT Jr, Stanley TB, Faggart JL, Wilson EMModulation of androgen receptor activation function 2 by testosterone and dihydrotestosteroneJ. Biol. Chem. v282, p.25801-25816 The androgen receptor (AR) is transcriptionally activated by high affinity binding of testosterone (T) or its 5alpha-reduced metabolite, dihydrotestosterone (DHT), a more potent androgen required for male reproductive tract development. The molecular basis for the weaker activity of T was investigated by determining T-bound ligand binding domain crystal structures of wild-type AR and a prostate cancer somatic mutant complexed with the AR FXXLF or coactivator LXXLL peptide....

MMDB ID: 6729 PDB ID: 1AFS Reference: Bennett MJ, Albert RH, Jez JM, Ma H, Penning TM, Lewis MSteroid recognition and regulation of hormone action: crystal structure of testosterone and NADP+ bound to 3 alpha-hydroxysteroid/dihydrodiol dehydrogenaseStructure v5, p.799-812 BACKGROUND: Mammalian 3 alpha-hydroxysteroid dehydrogenases (3 alpha-HSDs) modulate the activities of steroid hormones by reversibly reducing their C3 ketone groups. In steroid target tissues, 3 alpha-HSDs act on 5 alpha-dihydrotestosterone, a potent male sex hormone (androgen) implicated in benign prostate hyperplasia and prostate cancer....

Physical Property Value Units Temp (deg C) Source Melting Point 155 deg C EXP log P (octanol-water) 3.32 (none) EXP Water Solubility 23.4 mg/L 25 EXP Vapor Pressure 2.23E-08 mm Hg 25 EST Henry's Law Constant 3.53E-09 atm-m3/mole 25 EST Atmospheric OH Rate Constant 1.07E-10 cm3/molecule-sec 25 EST

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source mammal (species unspecified) LD50 oral > 5gm/kg (5000mg/kg) Toksikologicheskii Vestnik. Vol. (2), Pg. 6, 1996. rat LDLo intraperitoneal 326mg/kg (326mg/kg) LUNGS, THORAX, OR RESPIRATION: OTHER CHANGES Proceedings of the Society for Experimental Biology and Medicine. Vol. 46, Pg. 116, 1941.