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  • Title: 5alpha-Dihydrotestosterone (DHT) receptors in rat brain and pituitary cell nuclei.
    Author: Lieberburg I, Maclusky NJ, McEwen BS.
    Journal: Endocrinology; 1977 Feb; 100(2):598-607. PubMed ID: 832639.
    Abstract:
    Gonadectomized-adrenalectomized (GX-ADX) adult male rats were injected iv with 2-4 mug/kg [1,2-3H]DHT and sacrificed 2 h later. Whole tissue homogenates and purified cell nuclear fractions were prepared from various brain regions and the pituitary and analyzed for radioactivity. Cell nuclei from pituitary and most limbic-hypothalamic regions (but not cerebral cortex) concentrated radioactivity (per unit protein) over whole tissue levels. The highest levels of nuclear-associated radioactivity were present in pituitary, hypothalamic and septal tissues. Analysis of radioactivity by double isotope dilution, chromatography, and recrystallization revealed that unmetabolized DHT represented 96 and 95% of the nuclear-associated radioactivity in pituitary and pooled limbic-hypothalamic structures, respectively. Simultaneously administered 100-fold molar excesses of unlabeled 5betaDHT, progesterone or corticosterone did not reduce nuclear-retained [3H]DHT, while unlabeled 5alphaDHT competed strongly. The anti-androgen, cyproterone acetate, competed at doses capable of of blocking androgen-mediated neuroendocrine effects. Levels of nuclear-retained [3H]DHT were negligible in intact males, but rose markedly 24 h after castration-adrenalectomy, remaining stable for 2 weeks post-operatively. Density gradient centrifugation of pituitary or brain cell nuclear salt extracts (0.4M KCl) revealed the [3H]DHT bound to a macromolecule sedimenting at 3--4S. The characteristics of DHT brain and pituitary cell nuclear binding are compared with the respective characteristics of neural cytosol and ventral prostate nuclear androgen binding components. These preliminary data suggest the existence of the functional, steroid-specific, stereospecific cell nuclear androgen receptor in the adult rat brain and pituitary.
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