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Title: Steroid metabolism in normal and rheumatoid arthritic human subjects
Author: Somerville, Ian Ferguson
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1950
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The nature of the quantitative relationship between progesterone secretion and urinary pregnanediol excretion had been investigated by the quantitative determination of the metabolite after continued daily administration of progesterone to normal post-menopausal women, normal men, hysterectomised-ovariectomised women and hysterectomised post-menopausal women. These experiments prove that when the human body is subjected to the influence of progesterone for more than a few days, a progressive change in the relationship of hormone to metabolite occurs so that an increasing proportion of the administered hormone is recovered from the urine as the metabolite. This progesterone "priming" phenomenon has been shown to be attributable to a role of the uterus in the metabolism of progesterone. Pregnane -3a,20a-diol has been administered to post-menopausal women and the biochemical mechanism and clinical implications of these findings have been discussed. (2) The claim by de datteville et al. (1948) that pre-treatment with a-tocopherol augments the conversion of administered progesterone to urinary pregnanediol has been investigated. An identical experimental procedure has been adopted but normal human subjects have been studied in place of patients with carcinoma of the uterus or breast and the method of Sommerville, Gough and Marrian (1948) has been used instead of the modified method of Huber (1947). The results clearly indicate that a-tocopherol does not have the effect observed by de Watteville et al. when normal subjects are studied by the former method. Explanations are offered for these contradictory results. (3) A synthetic orally active progestogen-ethinyltestosterone - has been administered to normal men and the urine investigated for the presence of pregnanediol. Significant amounts of pregnanediol were not recovered from the urine but large amounts of an unidentified crystalline precipitate were observed. Excretion of this substance - which may be metabolite of ethinyltestosterone - as a glucuronide would account for the results obtained by Allen, Viergiver and Soule (1944) . The clinical implications of a progestogen which is not metabolised to pregnanediol have been discussed. (4) The excretion of urinary pregnanediol has been studied during normal pregnancy and the results have been compared with those obtained by less specific methods for the quantitative determination of the steroid. The results emphasise the necessity to establish values of pregnanediol excretion in normal pregnancy. (5) It has been shown that the method of Sommerville, Gough and Marrian (1948) is applicable to the determination of small amounts of pregnanediol in rabbit urine. The accuracy of the method when used for this purpose has been assessed and it is concluded that as little as 0.25 mg. of the steroid can be determined in one half of a twenty -four hour urine specimen. (6) «n analogy has been drawn between the intermediary metabolisms of progesterone and cortisone (17-hydroxy-11-dehydrocorticosterone) and it was anticipated on theoretical grounds that an abnormality of progesterone metabolism might be associated with rheumatoid arthritis. Such an abnormality was demonstrated in a large series of women and men with rheumatoid arthritis, and consisted in the conversion of an abnormally high proportion of administered progesterone to urinary pregnanediol. The abnormality was not observed in a series of patients suffering from diseases which resemble rheumatoid arthritis in one or more of their clinical features. The belief in the possibility that the pathology of rheumatoid arthritis is associated with an abnormality of steroid metabolism rather than with a deficiency of endogenous steroid secretion was strengthened by the observation that the abnormality is not affected by the administration of the adrenocorticotrophic hormone of the anterior pituitary gland. The biochemical mechanism and clinical implications of the abnormality of steroid metabolism have been considered and the rational of attempts to modify this abnormality has been discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available