Disease relevance of NSC 15460

• In castrated chicks, 5 alpha-DHT or 19-nortestosterone (19-NorT) inhibited growth as indicated by body weight, while testosterone and 5 beta-dihydrotestosterone (5 beta-DHT) were without effect [1].
• Induction of anovulatory sterility by neonatal treatment with 5 beta-dihydrotestosterone in female rats [2].

High impact information on NSC 15460

• These results have demonstrated that perinatal treatment with 5beta-dihydrotestosterone can induce such irreversible changes in the mammary glands, pituitary gland, ovaries, and genital tracts as those seen with other biologically active steroid hormones [3].
• The long-term effects on mammary glands of 5beta-dihydrotestosterone, considered to be biologically inactive, were studied in female SHN mice with mammary tumor, virus [3].
• Rises of [Ca2+]i evoked by 50 mm K+ -containing solution were suppressed in a concentration-dependent manner by testosterone (IC50, 3.1 nm) and by the nonaromatizable analog, 5beta-dihydrotestosterone (IC50, 6.9 nm) [4].
• Testosterone had no effect on Tfm/Y erythroid colonies, whereas 5 beta-DHT and 5 alpha-DHT significantly inhibited colony formation [5].
• However, similar in vivo treatment of Tfm/Y mice with testosterone or 5 beta-DHT had no effect on CFU-E colony formation [5].

Biological context of NSC 15460

• In this sense, 5alpha- and 5beta-dihydrotestosterone elicited a rapid positive inotropism in the isolated left atrium of the rat via cAMP-dependent mechanisms that may involve genomic effects [6].
• Stimulatory effects of 5 beta-dihydrotestosterone on the sexual behavior in the domestic chick [7].
• Both 5alpha and 5beta-dihydrotestosterone compounds exhibited less than 2% cross-reaction [8].
• Finally, 5 beta-dihydrotestosterone had also a strong affinity for the binding sites [9].
• The effect of 5 alpha-dihydrotestosterone and 5 beta-dihydrotestosterone on erythropoiesis of the newt, Triturus cristatus carnifex (Laur.) [10].

Anatomical context of NSC 15460

• Testosterone or 5 beta-dihydrotestosterone (5 beta-DHT) treatment (5 mg/kg) of Ta/Y mice in vivo before femoral bone marrow culture resulted in a significant increase in CFU-E colonies [5].
• At day 10, when the brain is particularly sensitive to the differentiating effects of gonadal steroids, formation of 5 alpha-DHT and 5 beta-DHT in the hypothalamus is higher in females than in males [11].
• In this sense, 5 alpha- and 5 beta-dihydrotestosterone-induced an acute positive inotropic effect in isolated left atrium of rat, an effect which may be due to cAMP-dependent mechanisms [12].
• A 1000-fold molar excess of radioinert 5 beta- or 5 alpha-DHT inhibited 5 beta-diol formation from [3H]T by cytosols and increased 5 beta-DHT formation [13].
• Production of 5 beta-dihydrotestosterone, 5 beta-androstane-3 alpha, 17 beta-diol and 5 alpha-dihydrotestosterone by the preoptic area did not differ between birds on long or short days [14].

Associations of NSC 15460 with other chemical compounds

• In wild male song sparrows, we examined the neural distribution of aromatase mRNA and seasonal changes in the activities of aromatase, 5 alpha-, and 5 beta-reductase, enzymes that convert T to 17 beta-estradiol, 5 alpha-dihydrotestosterone (5 alpha-DHT, a potent androgen), or 5 beta-DHT (an inactive metabolite), respectively [15].
• After the incubation of quail pituitary glands for 3 h with labelled testosterone four metabolites could be identified; androst-4-ene-3,17-dione, 5 beta-dihydrotestosterone (5 beta-DHT), 5 beta-androstane-3 alpha, 17 beta-diol and 5 alpha-DHT [16].
• 5 alpha-dihydrotestosterone was the only testosterone metabolite showing some behavioral effectiveness in castrates; estradiol and 5 beta-dihydrotestosterone failed to elicit sex behavior [17].
• Other steroids tested, Ad-dione 3 alpha or 3 beta-androsterone, 5 beta-DHT, epitestosterone, and progesterone had no effect on thymus or bone marrow [18].
• Incubation in the organ bath with an inhibitor of ornithine decarboxylase activity, alpha-difluoromethylornithine 10 mM, significantly decreased the positive inotropism induced by 5alpha- and 5beta-dihydrotestosterone (0.1-100 microM) [6].

Gene context of NSC 15460

• Testosterone or 5 beta-DHT added directly to Ta/Y marrow cultures caused an enhancement of CFU-E colony numbers compared with erythropoietin alone [5].
• The most important metabolites were 5 beta-dihydrotestosterone (5 beta-DHT), 5 beta-androstane-3 alpha, 17 beta-diol (5 beta-3 alpha-diol) and 5 beta-androstane-3 beta, 17 beta-diol [19].
• Furthermore, 6-min exposure to 5alpha- or 5beta-dihydrotestosterone significantly increased the activity of ornithine decarboxylase from 61.81+/-7.53 (control) to 93.28+/-9.45 and 80.28+/-12 pmol/h/mg of protein, respectively [6].
• Inhibitory kinetic constant determination of endogenous androgenic metabolites formed in the brain showed that preoptic aromatase is potently inhibited by 5 alpha-androstanedione(K(i)=6nM) and less strongly by 5 beta-dihydrotestosterone (K(i)=350nM) [20].
• The results are discussed with reference to a direct erythropoietin-independent action of 5 beta-DHT on erythroid stem cells [10].

Analytical, diagnostic and therapeutic context of NSC 15460

• Northern blot analysis showed that 5alpha- and 5beta-dihydrotestosterone did not modify the level of expression of the ornithine decarboxylase gene [6].

References