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Title: The possible significance of dehydroepiandrosterone in cystic fibrosis
Author: Gray, Christina E.
ISNI:       0000 0001 3512 4159
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1973
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The most consistent physical manifestations of cystic fibrosis in the male are abnormalities of the vasa deferentia, epididymes and seminal vesicles. These abnormalities of the male genital tract have been attributed by others to a failure in differentiation of the mesonephric duct at about the 10th to 12th foetal week. From the literatures incubation studies employing human-foetal testicular material have demonstrated dehydroepiandrosterone (DHA) to be an important pre-hormone of testosterone at this time. Thus DHA must be regarded as important in the maintenance of an androgenic environment necessary for the stabilisation of the mesonephric duct and its derivatives in the male foetus. It is accented that DHA and testosterone advance bone maturation which in children with cystic fibrosis is frequently retarded. Also, androgens are required for the maintenance of normal spermatogenesis. This process is known to be arrested at spermatocyte and spermatid stages in children with cystic fibrosis. DHA, then, is an important precursor of androgens (the 5 pathway being important during foetal development) and on its own account has widespread metabolic activity. Since tissues from a foetus known to have cystic fibrosis were not obtained, a study of dehydroeuiandrosterone production prenatally was not possible, However, a study of DHA in urine and blood samples collected from 48 children (from 1 to 20 years old) with cystic fibrosis was undertaken. R-51 Following addition of DHAS for recovery purposes, aliquots of urine from 24-hour collections were submitted to 6 hours hot hydrolysis at neutral pH (Fotherby, 1959), This hydrolytic method is specific for A'-3B-hydroxysteroid sulphates. This conjugated with glucuronic acid in urine was hydrolysed by a 24 hour incubation with p-glucuronidase (1,000 F.u. per ml urine) at 37°C employing a sulphatase inhibitor (potassium dihydrogen orthophosphate). Following extraction, purification by column chromatography and t.l.c. was effected. The dried residues were derivatised with benzenerheptafluorobutyric anhydride (1:1, v/v) for 30 minutes at 70°C and quantitation of the DHA ester was made by electron capture detection on a Pye 104 g.l.c. system. A correction was made according to the recovery of DHA added initially to urine samples. Group estimations of 17-oxosteroids, 17-oxogenic steroids and total 17-hydroxycorticosteroids were also made on the urine samples when sufficient urine was available. Plasma DBAS was estimated in 36 children (3 to 16 years of age) with cystic fibrosis according to the method of Brownsey et al. (l972). Levels of total 17-hydroxycorticosteroids excreted by children with cystic fibrosis, as presented in this thesis, are not significantly different from those of normal children and are thus in agreement with the findings of Chodos et al. (1965). The 17-oxosteroid excretion in affected patients from 1 to 10 years did not differ significantly from that of corresponding normal children. However, patients with cystic fibrosis in the 11 to 17 years age group had a significantly lower excretion of 17-oxosteroids than normal. DHA was detected in the urine of some children as young as 4 years of age and was found to be within the normal range in children up to 11 years of age. Excretion of DHA in the older age group (ll to 20 years) was subnormal in the majority of children with cystic fibrosis (in 8 of 11 boys and 6 of 7 girls). Circulating levels of DHAS were also significantly lower than normal in both males and females in the 11 to 15 years age range. From these results it is apparent that the increase in 17-oxosteroid excretion and the increase in plasma DHAS associated with normal puberty does not take place in the adolescent with cystic fibrosis even though clinical puberty may be well established, albeit at a later than average time. These findings reflect a failure in the maturation of the adrenal cortex and possibly also of the teste in the male.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available