Serum protein binding characteristics of cyproterone acetate, gestodene, levonorgestrel and norethisterone in rat, rabbit, dog, monkey and man
Identifieur interne : 000998 ( Istex/Curation ); précédent : 000997; suivant : 000999Serum protein binding characteristics of cyproterone acetate, gestodene, levonorgestrel and norethisterone in rat, rabbit, dog, monkey and man
Auteurs : Li Qi-Gui ; M. Hümpel [Allemagne]Source :
- Journal of Steroid Biochemistry [ 0022-4731 ] ; 1989.
Abstract
Protein binding characteristics including percentage of total binding, total binding capacity (pmol/mg protein), degree of specific binding, competition with dihydrotestosterone (DHT) and estradiol (E2) binding sites and dissociation constants (Kd) of low and high affinity binding sites were investigated for the progestins cyproterone acetate (CPA), gestodene (G), norethisterone (NET) and levonorgestrel (LN) in serum or plasma pools from man and four laboratory animal species (rat, rabbit, dog and monkey). Serum pools from animals were constructed from samples obtained either prior to or 1 day after pretreatment with ethinyl estradiol (EE;) (5 μg/kg/day for 7 days). Human plasma pools differed by SHBG levels (normal/induced). All serum pools were characterized by protein content and distribution. Equilibrium dialysis or dextran-coated charcoal (DCC) methods were used to separate bound and free steroids labelled with tritium.All progestins were highly (>80%) bound to proteins in all undiluted samples. Total binding capacity was highest in rat and lowest in moneky. Human plasma showed a capacity of 1.5–2.1 μg steroid/ml. In man, monkey and rabbit LN and G were specifically bound to the same degree as DHT, whereas NET binding was 50% lower. Specific binding of CPA to dog serum was 2–3 times higher than for other steroids. Two (high and low affinity) binding sites were found for LN, G and NET in man, monkey and rabbit and in dog for LN. Kd values for high affinity binding ranged from 3.5 (G in man) to 23 (NET in man) × 10−9 M. Kd values of low affinity binding varied from 0.5 (CPA in dog) to 4 (NET in man) × 10−6 M. E2 and DHT competition experiments confirmed the concept of SHBG as a carrier protein of 19-nor-progestins and DHT and its occurrence in man, monkey and rabbit. A sex hormone binding protein (SBP) in the dog seems to be responsible for the relatively high specific binding of CPA. SHBG is inducible by means of EE2 in man and monkey, but not in rabbit. EE2 may induce SBP in the dog. Comparison of in vitroKds (high affinity binding) and in vivo metabolic clearance rates showed the same rankings for LN, G and NET in man, monkey and rabbit.
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DOI: 10.1016/0022-4731(90)90291-Y
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Li Qi-Gui<affiliation><mods:affiliation>Research Centre of Reproductive Medicine, Tongji Medical University, Wuhan, P.R.C. China</mods:affiliation><wicri:noCountry code="subField">P.R.C. China</wicri:noCountry></affiliation>Le document en format XML
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Hümpel, HD Pharmakokinetik, Schering AG, Müllerstraβe 170-178, D-1000 Berlin 65, F.R.G..</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Author to whom all correspondence should be addressed: Dr M. 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China</mods:affiliation><wicri:noCountry code="subField">P.R.C. China</wicri:noCountry></affiliation></author><author><name sortKey="Humpel, M" sort="Humpel, M" uniqKey="Humpel M" first="M." last="Hümpel">M. Hümpel</name><affiliation wicri:level="1"><mods:affiliation>Author to whom all correspondence should be addressed: Dr M. Hümpel, HD Pharmakokinetik, Schering AG, Müllerstraβe 170-178, D-1000 Berlin 65, F.R.G..</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Author to whom all correspondence should be addressed: Dr M. Hümpel, HD Pharmakokinetik, Schering AG, Müllerstraβe 170-178, D-1000 Berlin 65</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Pharmacokinetics, Schering AG, Berlin/Bergkamen, F.R.G.</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Department of Pharmacokinetics, Schering AG, Berlin/Bergkamen</wicri:regionArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Steroid Biochemistry</title><title level="j" type="abbrev">JSTEB</title><idno type="ISSN">0022-4731</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1989">1989</date><biblScope unit="volume">35</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="319">319</biblScope><biblScope unit="page" to="326">326</biblScope></imprint><idno type="ISSN">0022-4731</idno></series><idno type="istex">6CAF3268A2FE5F9DF842104C64D12F068A472F09</idno><idno type="DOI">10.1016/0022-4731(90)90291-Y</idno><idno type="PII">0022-4731(90)90291-Y</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-4731</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Protein binding characteristics including percentage of total binding, total binding capacity (pmol/mg protein), degree of specific binding, competition with dihydrotestosterone (DHT) and estradiol (E2) binding sites and dissociation constants (Kd) of low and high affinity binding sites were investigated for the progestins cyproterone acetate (CPA), gestodene (G), norethisterone (NET) and levonorgestrel (LN) in serum or plasma pools from man and four laboratory animal species (rat, rabbit, dog and monkey). Serum pools from animals were constructed from samples obtained either prior to or 1 day after pretreatment with ethinyl estradiol (EE;) (5 μg/kg/day for 7 days). Human plasma pools differed by SHBG levels (normal/induced). All serum pools were characterized by protein content and distribution. Equilibrium dialysis or dextran-coated charcoal (DCC) methods were used to separate bound and free steroids labelled with tritium.All progestins were highly (>80%) bound to proteins in all undiluted samples. Total binding capacity was highest in rat and lowest in moneky. Human plasma showed a capacity of 1.5–2.1 μg steroid/ml. In man, monkey and rabbit LN and G were specifically bound to the same degree as DHT, whereas NET binding was 50% lower. Specific binding of CPA to dog serum was 2–3 times higher than for other steroids. Two (high and low affinity) binding sites were found for LN, G and NET in man, monkey and rabbit and in dog for LN. Kd values for high affinity binding ranged from 3.5 (G in man) to 23 (NET in man) × 10−9 M. Kd values of low affinity binding varied from 0.5 (CPA in dog) to 4 (NET in man) × 10−6 M. E2 and DHT competition experiments confirmed the concept of SHBG as a carrier protein of 19-nor-progestins and DHT and its occurrence in man, monkey and rabbit. A sex hormone binding protein (SBP) in the dog seems to be responsible for the relatively high specific binding of CPA. SHBG is inducible by means of EE2 in man and monkey, but not in rabbit. EE2 may induce SBP in the dog. Comparison of in vitroKds (high affinity binding) and in vivo metabolic clearance rates showed the same rankings for LN, G and NET in man, monkey and rabbit.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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