DHEA and the Intracrine Formation of Androgens and Estrogens in Peripheral Target Tissues: Its Role during Aging

@article{Labrie1998DHEAAT,
  title={DHEA and the Intracrine Formation of Androgens and Estrogens in Peripheral Target Tissues: Its Role during Aging},
  author={Fernand Labrie and Alain Bélanger and Van Luu‐The and Claude Labrie and Jacques Simard and L{\'e}onello Cusan and Jos{\'e}-Luis Gomez and Bernard Candas},
  journal={Steroids},
  year={1998},
  volume={63},
  pages={322-328}
}
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Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease.
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The last and key step in the formation of all estrogens and androgens is catalyzed by members of the family of 17beta-hydroxysteroid dehydrogenases (17 beta-HSDs), which provide each cell with the means of precisely controlling the intracellular concentration of each sex steroid according to local needs.
Minireview: Aromatase and the Regulation of Estrogen Biosynthesis-Some New Perspectives.
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C(19)-5-ene steroids in nature.
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An overview of the current understanding of the intracrine action of steroid hormones, which depends on the availability of the steroid precursors and transmembrane transporters for precursor uptake, and the enzymes involved in the E2-generating pathways in cancers of the endometrium and ovary are provided.
Dehydroepiandrosterone: A neuroactive steroid
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Local synthesis and effect of sex steroids in human skin and the hair follicle and hormonal effects on the wound healing response
TLDR
Results indicate an important role for local synthesis of E2 in skin from the circulating precursor DHEAS and expression of its action in the wound healing process as well as up-regulation of genes involved in inflammation, cell proliferation and differentiation and structural functions.
Aromatase--a brief overview.
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In principle, it should be possible to develop selective aromatase modulators (SAMs) that block aromat enzyme expression in breast, but allow unimpaired estrogen synthesis in other tissues such as bone.
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References

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Despite the fact that the concentration of dehydroepiandrosterone sulfate (DHEAS) in the circulation of adult men and women is higher than that of any other steroid, except cholesterol, the biologic
Physiological changes in dehydroepiandrosterone are not reflected by serum levels of active androgens and estrogens but of their metabolites: intracrinology.
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The present study demonstrates that the serum concentrations of testosterone, DHT, E1, and E2 are poor indicators of total androgenic and estrogenic activity, and the esterified metabolites of DHT appear as reliable markers of the total androgens pool.
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Repairing DHEA and DS to young adult levels in men and women of advancing age induced an increase in the bioavailability of IGF-I, as reflected by an increases in IGF- I and a decrease in IGFBP-1 levels.
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In the rat, a species having no significant secretion of adrenal androgens, plasma concentrations of DHEA and delta 4-dione maintained within the range of those found in adult men are efficiently converted into DHT and act as potent androgenic stimuli in prostatic tissue.
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TLDR
Blockade of DHT synthesized by these enzymes, with a pure antiandrogen of the class of flutamide, prolongs life in advanced prostate cancer, the effect being much more important when a small number of metastases is present.
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Evidence is presented that critical steps in the initiation process (mixed-function oxidase activation of a carcinogen) and promotion process (enhanced rates of cell proliferation and superoxide formation) all require NADPH and may be inhibited by DHEA and structural analogs as a result of a lowering of the NADPH cellular pool.
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