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Title: Metabolism of steroids in the adrenal cortex
Author: Griffiths, Keith
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1960
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A. Human Adrenal Gland Studies (i) Homogenates prepared from both fascicular and reticular zones of the adrenal cortex of man showed an equal ability to effect lap-hydroxylation in vitro. (ii) After in vivo administration of corticotrophin, homogenates of both zones showed an increase in 11f- hydroxylating activity. (iii) On incubating slices of both zones, corticotrophin caused a more marked stimulation of corticoid secretion from the fascicular than from the reticular zone slices. The most pronounced effect was on the production of hydrocortisone. (iv) 11(3 -Hydroxyandrostenedione was secreted by both zones. (v) Reticular tissue from the gland of a patient with Cushing's syndrome was significantly more responsive to corticotrophin in vitro than similar tissue from a 'normal gland'. (vi) A greater proportion of the cholesterol found in the non -stressed adrenal is localized in the fascicular zone in the cholesteryl ester form. The free cholesterol level is approximately the same in both types of tissue. However, the cholesterol depletion observed after stress or following corticotrophin administration appears to be at the expense of the ester form. From these results, aligned with reports of other workers, a mode of action of corticotrophin on the adrenal cortex has been suggested:- (a) A primary effect, which may involve mobilization of storage cholesterol by increased levels of corticotrophin both in the zona reticularis and at the fasciculata -reticularis border, resulting in an elevated presentation of steroid precursor. (b) A secondary effect, possibly as a consequence of an adaptation of enzyme systems to these increased levels of substrate, producing an elevated steroid metabolizing activity. B: Comparative Studies on Adrenals of Various Species (i) The rate of hydroxylation of DOC by adrenal homogenates is generally higher in those glands possessing a non -fatty cortex. (ii) There is no apparent relationship between the rate of 11P- hydroxylation of DOC by the adrenal, and the reported F/B ratio found in the adrenal venous effluent of the various species. (iii) An active 19- hydroxylase enzyme system has been demonstrated in the non -fatty type of adrenal gland, especially that of the golden hamster. 19- Hydroxylation has not yet been detected in the adult human adrenal cortex, although it has been observed with foetal adrenal tissue. (iv) The 19- hydroxylase appears to be associated with the inner regions of the cortex, whereas the 18- hydroxylase is localized exclusively in the zona glomerulosa. (v) SU )4885, known to inhibit 11P- hydroxylation, also inhibited the 19- hydroxylation reaction in the golden hamster adrenal.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available