Dehydroepiandrosterone radioactive

Furthermore Tait and co-workers [322] pointed out the marked difference in the urinary and blood production rates of testosterone obtained in women after injection of radioactive testosterone. He concluded that steroids produced from dehydroepiandrosterone contribute little to the blood production rate of androstenedione and testosterone in normal subjects [403]. According to Tait [324], all the blood production rate of androstenedione in the female and testosterone in the male is due to the same secreted steroid, while the blood production rate of testosterone in the female and androstenedione in the male is due about one-half to the same secreted steroid and one-half to converted precursor. The normal male secretes a ratio of testosterone to androstenedione of about 10 1 and the normal female secretes a ratio of androstenedione to testosterone of about 25 1. 

C]taurocholic acid (201) and [7-3H]dehydroepiandrosterone sulphate (202) in [2H5]glycerol matrix have been used184 to interpret the partial negative ion FAB spectra of these unlabelled compounds and to show that FAB and field desorption mass spetrometry enable one to determine quickly the specific radioactivity and label distribution within highly labelled biochemicals. The minimal specific radioactivities detectable by this method are about 20MBq/mmol and lOGBq/mmol for compounds labelled with 14C and with tritium, respectively, with 1% and 5% accuracy. The use of mass spectrometry minimizes interferences from labelled impurities. 

Roberts et ah (1964) answered part of the question by injecting doubly labeled cholesterol sulfate into the splenic artery (supplying 90% of the blood to an adrenal carcinoma) of a female patient and isolating various steroid sulfates in the urine of the first 24 hours. Of the recovered radioactivity 0.46% was dehydroepiandrosterone sulfate, bearing the same H/ S ratio as the injected compound. Urinary androstenediol-3-monosulfate and 5-pregnene-3/3,17a,20a-triol-3-monosulfate as well as 16a-hydroxydehydroepiandrosterone-3-monosulfate also had the same ratio as the injected cholesterol sulfate, demonstrating that all these compounds have a common sulfated precursor, which could possibly be cholesterol sulfate. 

Data obtained in vivo (Baulieu et al, 1965) have shown (Fig. 9) that after an injection of radioactive dehydroepiandrosterone and dehydroe-piandrosterone sulfate, the free compound is transformed more rapidly and more eflBciently into androsterone and etiocholanolone than the sulfo conjugate, the latter being apparently protected from rapid liver catabolism. 

Fig. 9. Urinary radioactive androsterone and SjS ndrosterone after injection of C-dehydroepiandrosterone (above) and H-dehydroepiandrosterone sulfate (below) (percentage of the injected radioadtivity).

After an injection of radioactive dehydroepiandrosterone sulfate, a small proportion is recovered as such in urine. However, if the double-labeled compound H-dehydroepiandrosterone sulfate- S is injected and its disappearance from the blood is observed, one finds different half-lives for H-dehydroepiandrosterone sulfate and for dehydroepiandrosterone sulfate- S (Fig. 10). This shows that there is a constant hydrolysis of the sulfo conjugate followed by a resulfation with sulfate from a large unlabeled pool (Fig. 3). In other words, the steroid moiety of dehydroepiandrosterone sulfate has a half-life of 9 hours, whereas the sulfate moiety has a shorter half-life of 6 hours, since the sulfate moiety is... 

Testosterone sulfate does not seem to be hydrolyzed in the organism, but its direct metabolites have not been identified, as only 3.5% of the radioactivity was found in urine after radioactive testosterone sulfate administration. Unlike dehydroepiandrosterone sulfate, testosterone sulfate is not transformed by indirect metabolism into estrogens during pregnancy (Dray, 1963). 

When radioactive tracers of dehydroepiandrosterone and dehydroepiandrosterone glucuronide are injected intravenously, the conversion of both compounds to dehydroepiandrosterone sulfate is nearly equivalent (contribution dehydroepiandrosterone glucuronide/ contribution dehydroepiandrosterone = 0.8). On the other hand, dehydroepiandrosterone glucuronide gives only 10% of the amount of androsterone obtained... 

In the fetal compartment dehydroepiandrosterone is largely converted into its 3 (J-.sulfate. After fetal perfusion with labeled dehydroepiandrosterone, 60-80% of the radioactivity of the adrenal tissues was present as dehydroC[)iandrosteroiie sulfate. These value.s dropped to 30-50% in the other fetal tissues (Boltb et at., 1966 Wengle, 1964, 1966). 

Fetal brain tissues also possess very active sulfokinases for dehydro-epjandro.steronc, and after incubation of tritium dehydroepiandrosterone with minced brain tissue from a human fetus in the twelfth week of gestation, 6% of the radioactive material consisted of ester sulfates (principally dehydroejnandrostcrone and androstenetriol sulfates). Moreover, the free fraction was largely metabolized to androstenediol, androstenetriol, and 16-ketoandrostenediol (Kiiapstein et al., 1968). 

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