Acidic steroid metabolites: Evidence for the excretion of C-21-carboxylic acid metabolites of progesterone in rabbit urine

Senciall, Ian R.; Dey, Arun C.

doi:10.1016/0022-4731(76)90147-3

Cited by 19 publications

(4 citation statements)

References 23 publications

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“…The liver, due to it large size, is undoubtedly the major site of steroid acid synthesis in the rabbit. C21-steroid carboxylic acids are also the major excretory products of progesterone metabolism in this species (18,19). The rabbit kidney possesses the enzymes to metabolize progesterone in vitro to a variety of reduced and polar neutral metabolites (56), comparable with those produced by liver homogenate (57).…”

Section: Discussionmentioning

confidence: 99%

“…Conversion of progesterone to DOC (14) and further oxidation of the a-ketol side chain to C21 and C20 carboxylic acids was also shown to occur with the rabbit liver microsomal fraction (15)(16)(17). The metabolism of progesterone to C21 carboxylic acids is a major metabolic pathway in the rabbit (18,19). Steroid acids have dso been identified as metabolites of adrenocorticoids in several other species, including man (20), and could represent important alternative metabolic pathways.…”

Section: Introductionmentioning

confidence: 90%

“…[4-14c]~regnenoic acid and nonlabelled pregnenoic acid were synthesized from [ 4 -l 4~] -~0 c and nonlabelled DOC, respectively, and purified as previously described (32,33). Nonlabelled steroids were purchased from Steraloids (Wilton, NH) and other supplies were obtained from previously reported sources (14)(15)(16)(17)(18)(19).…”

Section: Steroidsmentioning

confidence: 99%

“…identified in endocrine, hepatic, and other tissues and their participation in the metabolism of a wide variety of endogenous and xenobiotic substrates have been investigated (9,18). The adrenal cytockrome P-450 specific for steroid C21 hydroxylation has also recently been purified from bovine adrenocortical microsomes (1 1, 12).…”

Section: Introductionmentioning

confidence: 99%

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Progesterone C21 hydroxylation and steroid carboxylic acid biosynthesis in the rabbit. In vitro studies with endocrine, metabolic, and potential target tissues

Senciall¹,

Bullock²,

Rahal³

1983

Can. J. Biochem. Cell Biol.

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Progesterone C21-hydroxylase activity has been demonstrated with rabbit kidney microsomes for the first time and the formation of 21-hydroxy-4-pregnen-3,20-dione (DOC) by rabbit liver and kidney microsomes has been quantitated. Considerable intraspecies variability in enzyme activity occurred with both tissues. The liver enzyme (Vmax = 1.28-38.0 nmol/mg protein per 30 min of incubation) was significantly more active than the kidney enzyme (Vmax = 0.028-0.28 nmol/mg protein per 30 min of incubation). Apparent KM values were 1.39 and 0.8 microM, respectively. Cytochrome c (10(-5)M), potassium ferricyanide (10(-3)M), and 2-methyl-1,2-di-3-pyridyl-1-propanone (metyrapone; 10(-3)M) were strongly inhibitory with both tissues, whereas the liver microsomal system was less sensitive than the kidney to CO-air (90:10 v/v) inhibition. Metabolism of [14C]DOC to 4-pregnen-3,20-dione-21-oic (pregnenoic) and 4-androsten-3-one-17 beta-carboxylic (etienic) acids by liver microsomes and adrenal and ovary homogenates was differentially affected by several factors. CO-air (90:10 v/v), cytochrome c (10(-5)M), and metyrapone (10(-3)M) inhibited pregnenoic acid synthesis to a greater extent than etienic acid. Sodium cyanide had a stimulatory effect on the synthesis of pregnenoic acid by the liver but less consistent effects with other tissues. These results suggest that one or more cytochrome P-450 systems may be involved in the oxidation of progesterone through to pregnenoic acid by rabbit tissues.

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