Androgens

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An androgen is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. The major androgen in males is testosterone. It is the primary sex hormone and anabolic steroid in males. It is a steroid from the androstane class. It exerts its action through binding to and activation of the androgen receptor.

  • Androgen receptor. Ligand binding domain (LBD) containing an active site which binds intramolecularly the N-terminal FXXFL motif or coactivators with the same motif.[1] Water molecules are shown as red spheres. Human androgen receptor bound to testosterone (2ylo).
  • Heat shock factor (HSF) are transcriptional activators of heat shock genes. HSF bind to heat shock sequence elements throughout the genome with a consensus array of three oppositely oriented sequence AGGAN and activate transcription. Each HSF monomer contains one C-terminal and 3 N-terminal leucine zippers. Two sequences flanking the N-terminal leucine zippers contain the consensus nuclear localization signal (NLS). The DNA-binding domain (DBD residues 193-281) of HSF lies in the N-terminal of the first NLS region[2]. Depletion of HSF-1 is associated with accumulation of pathogenic androgen receptor in neurodegenerative diseases[3].
  • Cellular retinoic acid-binding protein (CRABP); Epididymal RABP (ERABP) is an androgen-dependent RABP present in the lumen of the epididymis believed to be involved in sperm maturation. ERABP binds specifically all-trans- and 9-cis-RA.
  • Aromatase. The primary function of aromatase is to produce estrogens by aromatizing androgens. Aromatase is the only known enzyme in vertebrates capable of catalyzing the aromatization of a six-membered ring[4].
  • Student Project 1 for UMass Chemistry 423 Spring 2015. Protein kinase C related kinase 1 (PRK1) is a component of Rho-GTPase, histone demethylase, androgen receptor, and histone demethylase signaling pathways and is involved in ovary and prostate cancer. A lot of PRK1 is expressed in cases of ovarian serous carcinoma.
  • Finasteride
  • Zolinza (Vorinostat)
  • Hydroxysteroid dehydrogenase, 17-β HSD is involved in the conversion of androstenedione to testosterone.
  • Aromatase converts androstenedione to estrogen and testosterone to estradiol.
  • Lipids: structure and classification
  • Cytochrome P450 3A4 (CYP3A4)


Human androgen receptor ligand-binding domain complex with modulator (PDB code 3b5r)

Drag the structure with the mouse to rotate

References

  1. ↑ Bohl CE, Wu Z, Chen J, Mohler ML, Yang J, Hwang DJ, Mustafa S, Miller DD, Bell CE, Dalton JT. Effect of B-ring substitution pattern on binding mode of propionamide selective androgen receptor modulators. Bioorg Med Chem Lett. 2008 Oct 15;18(20):5567-70. Epub 2008 Sep 5. PMID:18805694 doi:10.1016/j.bmcl.2008.09.002
  2. ↑ Sarge KD, Murphy SP, Morimoto RI. Activation of heat shock gene transcription by heat shock factor 1 involves oligomerization, acquisition of DNA-binding activity, and nuclear localization and can occur in the absence of stress. Mol Cell Biol. 1993 Mar;13(3):1392-407. PMID:8441385
  3. ↑ Kondo N, Katsuno M, Adachi H, Minamiyama M, Doi H, Matsumoto S, Miyazaki Y, Iida M, Tohnai G, Nakatsuji H, Ishigaki S, Fujioka Y, Watanabe H, Tanaka F, Nakai A, Sobue G. Heat shock factor-1 influences pathological lesion distribution of polyglutamine-induced neurodegeneration. Nat Commun. 2013;4:1405. doi: 10.1038/ncomms2417. PMID:23360996 doi:http://dx.doi.org/10.1038/ncomms2417
  4. ↑ Ghosh, D., Griswold, J., Erman, M., Pangborn, W. " X-ray Structure of Human Aromatase Reveals An Androgen-Specific Active Site" Journal of Steroid Biochemistry and Molecular Biology. [Online] 2010,Vol. 118, Issue 4-5, p197-202[1]

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