Linked Life Data

7556779

Source:http://linkedlifedata.com/resource/pubmed/id/7556779

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1995-11-8
pubmed:abstractText
TZP-4238 suppresses plasma testosterone in humans, but its action on the androgen biosynthesis pathway has not been established. Therefore, we researched the testicular testosterone level and the testosterone biosynthesis pathway in vitro in rats before and after receiving a single or continuous oral dose of TZP-4238. The total testosterone fell to 60% of the basal level within 3-8 hr (p < 0.05) and then returned to the control concentration by 24 hr after a single administration of 32 mg/kg. The alteration of the plasma testosterone level correlated well with that of the intratesticular level, which was decreased to 50% at 3-8 hr and recovered to the control level by 24 hr. However, the decrement of the plasma LH level at 3-8 hr after a single oral administration was slight and it then returned to the original level at 12 hr. During the 8 weeks of daily administration of 0.5 mg/kg of TZP-4238 or chlormadinone acetate to dogs, the plasma testosterone levels were slightly lower than the basal extent. In vitro experiments were conducted on the rat testis using the exogenous precursor steroids 20 alpha-hydroxycholesterol, pregnenolone and progesterone, in various steps leading to the biosynthesis of testosterone. Trilostane acted at 3 beta-hydroxysteroid dehydrogenase (50% inhibition concentration, IC50 was 1 microM), ketoconazole inhibited the 17 alpha-hydroxylase, and C20, 22- and C17, 20-lyase activities, with an IC50 of 1-50 microM. Cyproterone acetate inhibited both the 3 beta-hydroxysteroid dehydrogenase (IC50;50 microM) and C17, 20-lyase. On the other hand, TZP-4238 exhibited a weaker inhibition of 3 beta-hydroxysteroid dehydrogenase (IC50; 100 microM) than cyproterone acetate, but not of hydroxylase and lyase. Though TZP-4238 did not inhibit the increased testosterone level induced by hCG, trilostane markedly inhibited the effect induced by hCG.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
jpn
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0029-0661
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
679-94
pubmed:dateRevised
2011-7-27
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
[The effects of antiandrogen TZP-4238 on plasma testosterone and LH and steroidogenesis in rat and canine testis].
pubmed:affiliation
Pharmacokinetics Research Department, Teikoku Hormone Mfg. Co. LTD, Kawasaki, Japan.
pubmed:publicationType
Journal Article, In Vitro, English Abstract