Steroidal studies in vascular disease

Duffy, Thomas (1969) Steroidal studies in vascular disease. PhD thesis, University of Glasgow.

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Abstract

A method is described for determining the 11-deoxy-17-oxosteroids (D.17-0S), dehydroepiandrosterone (DHA), aetiocholanolone (E), androsterone (A) and epiandrosterone (epiA) in the sulphate (S) and glucuronide (G) fractions of urine. Internal standards pregnenolone and pregnenolone sulphate were added to separate aliquots of urine and the steroid corepgates isolated and cleaved separately. The steroid extracts were purified by alumina column chromatography, then the steroids were separated and quantitated by gas-liquid chromatography as their trimethylsilyl either derivatives. Absolute and relative recoveries for the method were satisfactory. The method was specific and reproducable and sufficiently sensitive to determine 0.1 mugm of steroid/25 ml of urine. 2. Thirty-seven normal males (22) and females (15) were studied. Their urinary steroid levels were:- [table] The above values for males compare favourably with those for other investigators whereas those for the females are low. The study revealed hitherto unrecognised correlations between individual urinary D.17-0S. Therefore, understandably, the urinary excretion of steroid conjugates showed definite patterns:- [table] The E.S/A.S, E.G/A.G and E.(S+G)/A.(S+G) ratios were significantly higher for females. Possible reasons for the above differences were discussed. 3. Thirty-two hypertensive males (15) and females (17) were studied. The hypertensive males excreted significantly less epiA.S (P = 0.056), DHA.S (P = 0.067) and A.G (P = 0.028), than normal controls. They also showed significantly higher ratios for epiA.S/A.S (P = 0.0008), DHA.S/E.S (P = 0.0001), A.S/E.S (P = 0.0004), E.G/A.G (P = 0.00004). As with normal males the individual D.17-0S were highly intercorrelated, but no set pattern for steroid sulphate excretion arose, that for glucuronide conjugates was E.G>A.G>DHA.G. The urinary steroid levels for the hypertensive females showed no significant differences compared with normal controls. On the basis of the present results together with those for previous investigations a theory to explain the abnormal urinary D.17-0S patterns in hypertension is presented. The theory also attempts to accommodate the other steroid abnormalities presented in hypertension. 4. Incubation studies on the effect of DHA on steroid hydroxylation in human adrenal tissue demonstrated an inhibitory action by DHA. 14C-progesterone and 3H-DOC were metabolised to a much lesser extent by incubations containing DHA than those without. The results supported the increased steroid hydroxy-lation found in hypertension. 5. Studies on the effect of varying salt intake on the excretion of D.17-0S conjugates were carried out. The results of 4 of the 6 subjects demonstrated a relationship between salt and D.17-0S metabolism. One subject showed a marked increase in D.17-0S excretion after increasing his salt intake and in 2 other subjects there was a very dramatic drop in D.17-0S sulphate excretion on decreasing their salt intake. The hypertensive female showed significant decreases in the excretion of D.17-0S sulphates after decreasing her salt intake and significant increases after increasing her salt intake. Intravenous saline infusion resulted in increased salt excretion concomitant with increased excretion of D.17-0S. These results were interpreted in terms of a "salt-losing" steroid and its possible role in hypertensive disease.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: J N Davidson
Keywords: Endocrinology
Date of Award: 1969
Depositing User: Enlighten Team
Unique ID: glathesis:1969-72968
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 11 Jun 2019 11:06
URI: http://theses.gla.ac.uk/id/eprint/72968

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