Age- and Sex-Dependent Biotransformation of Androgens in the Pituitary, Pineal Gland, and Arcuate Nucleus of the Hypothalamus of Rats

Degtiar, W G; Pavlinov, S. A.; Loseva, L. A.; Isachenkov, W. A.

doi:10.1007/978-3-642-66885-2_46

Cited by 2 publications

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“…Androgen metabolites in bone tumor samples were assayed as described elsewhere with minor modification [6]. Bone tumor samples were powdered in liquid nitrogen using a porcelain mortar, and 0.05 M Na-phosphate buffer (pH 7.4) in a volume of 700 pl/ 200 mg tissue was added.…”

Section: Methodsmentioning

confidence: 99%

Synthesis of 5α-dihydrotestosterone in human bone tumors of various histological structure

Degtyar¹,

Babkina²,

Кушлинский³

et al. 1999

Bull Exp Biol Med

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In human primary bone tumors of various histological origins, metabolism of testosterone led to the formation of 5o~-reduced metabolites (mainly 5c~-androstane-3a,17[3-diol, and 5a-androstane-3[3-1713-diol), but not 5o~-dihydrotestosterone. Transformation of 5r testosterone to other metabolites in human primary osteosarcomas is assumed to be associated with its inactivation or involvement of metabolites of this androgen in unknown regulatory mechanisms in bone tumors. Therefore, in vitro evaluation of 5~-reductase activity in human primary osteosarcomas and other tumors by 5o~-dihydrotestosterone formation could yield erroneous results. Key Words: bone tumors; androgens; metabolismPathogenesis of bone tumors is obviously associated with enhanced androgen biosynthesis. On the other hand, these tumors can produce some androgens [1,2,4]. This implies the involvement of androgens in the regulation of some functions in bone tumors and the presence of androgen-metabolizing enzymes in the bone tissues.Metabolism of androgens in various target tissues has long been studied, but the data on bone tissues are contradictory. These tissues were shown to express some enzymes of androgen metabolism [1 1,12].Our recent experiments showed that androgens are metabolized in human primary osteosarcomas containing the main enzymes of androgen metabolism. Activities of 3o~-hydroxysteroid oxidoreductase (3~-HSOR) and 3[3-hydroxysteroid oxidoreductase (313-HSOR) far surpassed those of other enzymes. In spite of relatively high activity of A4steroid:NAD(P)-oxidoreductase (5(z-R) in osteosarcomas, biotransformation of testosterone did not lead to the formation of 5~-dihydrotestosterone (5o~-DHT) in the majority of tumors. However, other 5~-reduced metabolites, 5cz-androstane-3~, -androstane-313,1713-diol (3[3-D) were found in these tumors.Here we compared the formation of 5~-DHT from testosterone in osteosarcoma, chondrosarcoma, and giant cell tumor and benign bone neoplasms. MATERIALS AND METHODSPatients with osteosarcoma (n=19), chondrosarcoma (n=10), giant cell bone tumor (n=7), and benign bone tumor (n=5) were examined.Testosterone androgens 5~-DHT, 3~-D, 313-D, 5~-androstane-3,17-dione, 4-androstene-3,17-dione (A4) were form Sigma, and other reagents from Merck and Beckman. [ 1,2,6,7-3H]-Testosterone (3H-testosterone, specific activity 80-110 Ci/mmol) and 5~-dihydro-[1,2,6,7-3H]-testosterone (3H-DHT, specific activity 80-105 Ci/mmol, Amersham) were used.Silufol plates (15x15 cm) coated with Silica gel (100 ~t) were used for separation of metabolites and purification of 3H-testosterone and 3H-DHT. Chromatography was performed 3 times in benzene:acetone: ethanol system (9:1:0.5 volume ratio). This procedure allowed us to separate not only the main androgen metabolites, but also 3c~-D and 313-D stereoisomers.

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Section: Methodsmentioning

confidence: 99%

Synthesis of 5α-dihydrotestosterone in human bone tumors of various histological structure

Degtyar¹,

Babkina²,

Кушлинский³

et al. 1999

Bull Exp Biol Med

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“…We demonstrated that metabolites produced from 3[3-D are more chromatographically polar compounds than 3[3-D. It was proposed that these compounds possess an additional hydroxyl group [5]. This assumption was confirmed by the data showing that metabolism of 313-D in rat pituitary gland yields 5ct-androstane-3~,6t~, 17[3-triol, 5ct-androstane-3[~,713,17~-triol, and 5~-androstane-3 [3,7t~, 17~-triol [33 ].…”

Section: N N Blokhin Russian Ontological Research Center Russian Amentioning

confidence: 95%

“…Furthermore, neither DHT, nor 3o~-D, but only polar compounds, are in vitro formed from 3~-D in both brain structures [5,20]. Our previous experiments demonstrated the formation of polar compounds from DHT and 3~-D in the pituitary gland and hypothalamus of male and female rats, but in this case polar compounds were not the only metabolites [5,20]. We demonstrated that metabolites produced from 3[3-D are more chromatographically polar compounds than 3[3-D.…”

Section: N N Blokhin Russian Ontological Research Center Russian Amentioning

confidence: 96%

“…It remained unclear, whether or not the scheme of androgen metabolism in the prostate is applicable to this process in rat pituitary gland. We first studied in vitro metabolism of not only testosterone, but also of 5a-dihydrotestosterone (DHT), 5~-androstane-3~, 1713-diol (3cx-D), and 313-D in rat pituitary gland and hypothalamus [5,20]. We revealed some peculiarities of androgen metabolism in these structures of rat brain.…”

Section: N N Blokhin Russian Ontological Research Center Russian Amentioning

confidence: 99%

“…The discovery of androgen metabolism in rat brain in the late 1960s [58] has attracted much attention to this problem. The metabolism of testosterone was found in many brain structures [ 19,23,45,47,51,55,57], in particular in rat pituitary gland. The intensity of testosterone metabolism in the pituitary gland of male rats is 1/5 of that in the prostate, the main androgen target tissue [22].…”

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confidence: 99%

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Metabolism of androgens in rat pituitary gland and hypothalamus: Catabolism of dihydrotestosterone or transformation of androgen signal?

Degtyar

Kushlinskii

2000

Bull Exp Biol Med

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The role of androgen metabolism and individual androgen metabolites in rat pituitary gland and hypothalamus is discussed on the basis of published data and results of our experiments. It is proposed that metabolism of androgens in these structures is aimed at the formation of not only true sex steroids estradiol-17 beta and 5 alpha-dihydrotestosterone, but also of androgens contributing to the regulation of cell processes, i.e. represents modification (transformation) of androgen signal (testosterone) in target pituitary and hypothalamic cells.

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Age- and Sex-Dependent Biotransformation of Androgens in the Pituitary, Pineal Gland, and Arcuate Nucleus of the Hypothalamus of Rats

Cited by 2 publications

References 0 publications

Synthesis of 5α-dihydrotestosterone in human bone tumors of various histological structure

Synthesis of 5α-dihydrotestosterone in human bone tumors of various histological structure

Metabolism of androgens in rat pituitary gland and hypothalamus: Catabolism of dihydrotestosterone or transformation of androgen signal?

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