Functional Alterations of the Pituitary-Adrenal Axis: Morphological Studies in the Rat

Kubba, Mahir Abdul Ghani (1987) Functional Alterations of the Pituitary-Adrenal Axis: Morphological Studies in the Rat. PhD thesis, University of Glasgow.

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The factors involved in the regulation of corticotroph growth and differentiation in the anterior pituitary gland are not well understood. However, alterations in the function of these cells are known to result in changes not only in the morphology of individual cells, but also in the size of the corticotroph population. In the studies included in this thesis specific manipulations of corticotroph function were performed in the Sprague-Dawley rat. Qualitative and quantitative assessment of the morphological changes occurring in corticotrophs was made at light microscopic and ultrastructural levels. Because of sex differences in the pituitary - adrenal axis in the rat, and to allow comparison with previous work in specific areas some of the studies have been performed in both sexes, others in only one. In Chapter one, relevant aspects of the control of corticotroph function are reviewed, concentrating mainly on stimulation by corticotrophin - releasing factor (CRF) and vasopressin (VP) and inhibition by glucocorticoid negative feedback. Current knowledge on the factors controlling corticotroph growth and differentiation is also reviewed. In Chapter two, the quantitative changes in the corticotroph population of the female rat were monitored at 2 and 6 weeks after bilateral adrenalectomy, using the steroleogical measurement, volume density (Vv) . This showed a three-fold increase, which is greater than the two-fold increase previously reported in the male rat. Daily administration of CRF to male rats produced a dose-dependent increase in corticotroph Vv, although this was much lower than that achieved by adrenalectomy. VP produced a further increase in Vv when given with lower doses of CRF, but not with high dose (50mug/Kg). In Chapter three, corticotroph Vv was examined following functional inhibition by the synthetic glucocorticoid, dexamethasone. Daily administration in doses up to 500mug/Kg for six weeks to female rats did not produce a significant fall in corticotroph Vv, despite apparent inhibition of adrenocorticotrophin (ACTH) release. This is discussed in the light of biochemical data on the action of dexamethasone. The effects of long-term (26 weeks) inhibition of function were difficult to interpret because of the non-specific catabolic effects of the steroid. These problems are discussed. In addition, following withdrawal of dexamethasone, the recovery of the axis was followed up to 14 days. In Chapter four, qualitative ultrastructural changes were examined. The reported changes occurring in male rats were confirmed and extended to 6 weeks after adrenalectomy. The changes in females were documented for the first time, and as with the light microscopic studies suggested a more marked response than in the male. The changes following dexamethasone administration were monitored, and showed a general increase in granulation of corticotrophs in both sexes. These findings were different from the changes seen with corticosterone, where there was mainly a decrease in granulation in the male rat, and an increase in the female. The possible reasons for these findings are discussed. Quantitative analysis of cell area was performed in stimulated corticotrophs, to assess the degree of hypertrophy. The results were in keeping with a greater response in the female than in the male, and with a role for CRF in the production of hypertrophy. The subjective assessment of an increase in granule size in stimulated corticotrophs was confirmed. In dexamethasone inhibited corticotrophs, a reduction in granule diameter was demonstrated in both sexes but only in the male after corticosterone. In Chapter five, the mitotic activity was measured in the normal pituitary, and following bilateral adrenalectomy and CRF administration using a metaphase arrest technique. A significant circadian rhythm was demonstrated with a peak at 1100 and a trough at 2300. Following adrenalectomy, a significant increase in general mitotic index was demonstrated only at 7 days, although mitoses in corticotrophs were increased at 2 days. The reasons for this apparent delay are discussed. CRF induced a more marked general increase than adrenalectomy at 2 days and levels were still significantly increased by 7 days. This appeared to be due mainly to an increase in mitoses in a non-corticotroph population. These findings are discussed. Chapter 6 consists of a general discussion of the results.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Neurosciences
Date of Award: 1987
Depositing User: Enlighten Team
Unique ID: glathesis:1987-77481
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 09:07
Last Modified: 14 Jan 2020 09:07

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