Actions of corticotrophin on the human adrenal cortex

Studzinski, George Prezemyslav (1962) Actions of corticotrophin on the human adrenal cortex. PhD thesis, University of Glasgow.

Abstract

Studies made on the adrenal cortex of glands removed by operation on women with breast carcinoma indicate that the effects of preoperative administration of corticotrophin depend to a large extent on the degree of purity of the corticotrophin preparation used. Crude preparations of corticotrophin cause a marked increase in adrenal weight and mitotio activity and result in the striking alteration of histological appearances of the adrenal cortex previously described by Symington et al., (1956). On the other hand, administration of corticotrophin concentrated by oxycellulose adsorption and further purified by column chromatography leads to a slight increase in adrenal weight and mitotic activity and causes less alteration in histological appearances of the adrenal cortex. These findings appear to support the view of Stack-Dunne and Young (1954) that there may be more than one pituitary factor with effects on the adrenal cortex. Measurements of the weight of 30 adrenal glands removed by operation from those patients gave a mean weight of 4.0 g. This is the first reported series of observations on the weight of adrenal gland in living subjects who were not preoperatively treated by corticotrophin or cortisone. Administration of all types of corticotrophin to patients who were adrenalectomised four days later show a marked increase in activity of an enzyme of the pentose phosphate cycle, (the glucose-6-phosphate dehydrogenase). Other dehydrogenases which reduce nico-tinamide-adenine dinucleotide phosphate were also studied but do not show significant increases in man, though they do increase in activity after corticotrophin administration in the rat and the guinea pig adrenal cortex. The increase in gluoose-6-phoaphate dehydrogenase noted in the human adrenal cortex is of the same magnitude whether adrenal growth is slight or intense, and is maximal in the region of the cortex which corresponds to the interface between the "clear" and "compact'' cells. These cells normally are typical of the zona fasciculata and zona reticularis, respectively. The above findings are discussed in relation to the theory of the mechanism of corticotrophin action proposed by Haynes, and are taken to give this theory further support. The in vitro response to corticotrophin of slices of human adrenal cortex removed by operation was also studied, and some properties previously found to characterise the adrenal tissue of the rat under in vitro conditions are found to apply to human adrenal tissue. In particular, it was demonstrated that adenosine-3',5'-cyclic mono-phosphate can stimulate corticosteroid output to the same extent as corticotrophin. Human adrenal tissue, however, was found to be 1000 times more sensitive to corticotrophin than rat adrenal tissue. It was also noted that in-vitro incubation does not ensure complete cell survival in the adrenal slices; clear cells are more vulnerable than compact cells. Slices obtained from adrenal glands removed from patients with Cushing's Syndrome or from patients receiving corticotrophin pre-operatively, responded to corticotrophin less well than those from normal glands. On the other hand, slices out from the so called non-functioning nodules found in the adrenals of patients with no endocrine symptoms, responded in vitro to corticotrophin with higher corticosteroid production than was observed when slices from normal glands were so treated. It is concluded that secretion of steroids by human adrenal cortex in vitro in response to corticotrophin, does not represent the truly physiological process taking place under the normal conditions, but depends entirely on the conversion of easily convertible stored precursors, and the magnitude of the response depends entirely on the quantity of the precursors which happen to be present in the cells at the time of the removal from the body.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: J K Grant
• Keywords: Endocrinology, Pharmacology
• Date of Award: 1962
• Depositing User: Enlighten Team
• Unique ID: glathesis:1962-72063
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 17 May 2019 13:09
• Last Modified: 17 May 2019 13:09
• URI: https://theses.gla.ac.uk/id/eprint/72063