Purification of androgen receptors in human sebocytes and hair.
University of Miami School of Medicine, Department of Dermatology and Cutaneous Surgery, FL 33101.
J Invest Dermatol, 1992 Jun, 98:6 Suppl, 92S-96S
Human sebaceous glands (SG) and hair follicles (HF) are target structures in the skin for androgen action. They contain steroid enzymes, capable of transforming weak androgens into the target-tissue-active androgens testosterone (T) and dihydrotestosterone (DHT), which bind to the androgen receptor (AR) to regulate cellular transcription. The AR from HF and SG from human scalp tissue has been purified greater than 86,000 times by phenyl-sepharose, DEAE-sephacel, gel filtration chromatography, and ultrafiltration. Sucrose density gradient analysis and non-denaturing gradient polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate (SDS)-PAGE revealed two molecular species of AR, an active form called monomer, capable of binding DHT with great specificity (4S, m = 62,000 Da, Kd = 0.6 nM, Bmax 8260 fmol/micrograms protein), and the other, an inactive form of the monomer called tetramer (10.8S, m = 252,000 Da, Kd = 2.9 nM). The two species are interconvertible, and after purification each appeared as a single band on SDS-PAGE. The conversion of the monomer to the tetramer AR form is influenced by reduced and oxidized glutathione, and possibly by an endogenous disulfide converting factor (DCF). Furthermore, biochemical events in the androgenic signal transduction sequence were shown to be stimulated by androgens via the AR. These include the total nuclear AR content, chromatin binding of AR complexes, and stimulation of RNA polymerase II, thus influencing gene expression, which is important in understanding regulation of HF growth and SG proliferation.
There are enzymes in within the follicle and the sebaceous glands that turn weak androgens into tissue-specific androgens such as DHT. One enzyme I refer to is one form of 5-alpha-reductase. Then there are the androgen receptors which react when these androgens are present. Still with me ? :)
These people purified the androgen receptors AND found out that there are two species of them which are interconvertible: they are called the monomer AR and the tetramer AR. Monomer receptor is ,for us, the EVIL one. Its the active form of the receptor and the one that responds to stuff like DHT. Tetramer is a passive androgen receptor which does not react to DHT. So androgen receptors in the tetramer mode would be great news for guys with MPB.
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