RESUMO
Rat adrenal gland preparations were incubated with 23,24-dinor-5-cholen-3 beta-ol (Guneribol), a proposed intermediate in the sesterterpene pathway for steroid biosynthesis. Steroids were isolated, purified by thin layer and high-performance liquid chromatographies and crystallized to constant specific activity. These preparations converted the substrate to 23,24-dinor-4-cholen-3-one. Radioactive 23,24-dinor-4-cholen-3-one was synthesised and incubated with further tissue preparations and shown to be converted to corticosteroids. These findings suggest that 23,24-dinor-4-cholen-3-one is an intermediate on the sesterterpene pathway for steroidogenesis.
Assuntos
Corticosteroides/biossíntese , Glândulas Suprarrenais/metabolismo , Pregnenos/metabolismo , Terpenos/metabolismo , Corticosteroides/isolamento & purificação , Animais , Radioisótopos de Carbono , Colesterol/metabolismo , Microssomos/metabolismo , Técnica de Diluição de Radioisótopos , Ratos , Sesterterpenos , TrítioRESUMO
Rat and human adrenal gland preparations were incubated with radioactive cholesterol and 23,24-dinor-5-cholen-3 beta-ol, the latter being a proposed intermediate in the sesterterpene pathway for steroid biosynthesis. Steroids were isolated, purified by TLC and crystallised to constant specific activity. It was found that rat and human adrenal glands can utilise 23,24-dinor-5-cholen-3 beta-ol to produce androstenedione and dehydroepiandrosterone. Also, it was found that the conversion of 23,24-dinor-5-cholen-3 beta-ol to androgens occurs in the microsomal fraction. It was concluded that the sesterterpene pathway for steroid biosynthesis can function in the rat and human adrenal glands to produce androgens and that the intermediates are converted to androgens in the microsomal fraction.
Assuntos
Neoplasias das Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/metabolismo , Androgênios/biossíntese , Animais , Biotransformação , Humanos , Microssomos/metabolismo , Mitocôndrias/metabolismo , Ratos , Terpenos/metabolismoRESUMO
Rat and rabbit testis preparations were incubated with [4-14C]cholesterol and 23,24-dinor-[7 alpha-3H]5-cholen-3 beta-ol, the latter being a proposed intermediate in the sesterterpene pathway for steroid biosynthesis. Steroids were isolated, purified by thin-layer chromatography and crystallised to constant specific activity. It was found that rat and rabbit testis can utilise 23,24-dinor-5-cholen-3 beta-ol to produce testosterone. The tritium/carbon-14 ratios in the testosterone and androstenedione isolated indicated that these tissues differentiated between the two substrates. This finding is supported by the observation that, on stimulation with HCG, the tritium/carbon-14 ratios in the testosterone isolated were increased compared to the controls. The results of further experiments implied that, while the biosynthesis of testosterone from cholesterol occurred in the rat testis mitochondrial fraction, its biosynthesis from 23,24-dinor-5-cholen-3 beta-ol occurred in the microsomal fraction.
Assuntos
Androstenodiona/biossíntese , Testículo/metabolismo , Testosterona/biossíntese , Animais , Colesterol/metabolismo , Masculino , Microssomos/metabolismo , Mitocôndrias/metabolismo , Pregnenolona/análogos & derivados , Pregnenolona/metabolismo , Coelhos , Ratos , Sesterterpenos , Terpenos/metabolismoRESUMO
Horse fetal gonadal tissue was incubated with 3 beta-hydroxy-5,7-pregnadien-20-one and 5,7-cholestadien-3 beta-ol and it was shown that both substrates were converted to 3 beta-hydroxy-5,7-androstadien-17-one. These findings support the proposal that in this tissue there is a 5,7-diene pathway producing 3 beta-hydroxy-5,7-androstadien-17-one, the putative precursor of equilin in the placenta.
Assuntos
Androstadienos/biossíntese , Gônadas/embriologia , Animais , Cromatografia Líquida de Alta Pressão , Desidrocolesteróis/metabolismo , Feminino , Gônadas/metabolismo , Cavalos , Pregnadienos/metabolismo , GravidezRESUMO
Rat adrenal gland preparations were incubated with radioactive cholesterol and 23,24-dinor-5-cholen-3 beta-ol. Steroids were isolated, purified by thin-layer and high performance liquid chromatography and crystallised to constant specific activity. It was found that the rat adrenal gland can utilise 23,24-dinor-5-cholen-3 beta-ol to produce corticosterone. Also, in contrast to the conversion of cholesterol to corticosterone which occurs in the mitochondrial fraction, the conversion of 23,24-dinor-5-cholen-3 beta-ol to corticosterone occurs in the microsomal fraction. It was concluded that the sesterterpene pathway for steroid biosynthesis can function in the rat adrenal gland and that the intermediates are converted to steroid hormones in the microsomal fraction.
Assuntos
Glândulas Suprarrenais/metabolismo , Esteroides/biossíntese , Animais , Fenômenos Químicos , Química , Colesterol/metabolismo , Corticosterona/biossíntese , Hidroxilação , Técnicas In Vitro , Microssomos/metabolismo , Mitocôndrias/metabolismo , RatosRESUMO
The production of equilin and the other ring B-unsaturated estrogens by the pregnant mare is anomalous in that they are biosynthesised by a cholesterol-independent pathway. Fetal horse gonads were incubated with tritiated sodium acetate and radiochemically pure 3 beta-hydroxy-5,7-pregnadien-20-one and 3 beta-hydroxy-5,7-androstadien-17-one were isolated. A fetal gonad--placental system is proposed for equilin production, 3 beta-hydroxy-5,7-pregnadien-20-one being a precursor for 3 beta-hydroxy-5,7-androstadien-17-one in the fetal gonad and the latter being the precursor of equilin in the placenta. The nature of the possible precursor of 3 beta-hydroxy-5,7-pregnadien-20-one is discussed.
