Investigations into the mechanism of action of oestradiol-17beta

Billing, Ronald J (1969) Investigations into the mechanism of action of oestradiol-17beta. PhD thesis, University of Glasgow.

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Cells proliferated from explants of immature rat Uterus when the latter were placed in a specific culture medium. Although most of the cells died after 8 or 9 days auto-radiographic studies showed that at earlier times the cello were synthesising both RNA and DNA. Therer was no detectable change in the growth pattern when oestrogen was added to the culture medium, but increased growth occurred when the hormone was administered to the rat before death. Autoradiographic localisation Of 3H oestraiol-17beta showed that in the cultured cells the hormone was spread throughout the cells, but in smeared Uterine cells taken directly from the animal there was evidence of localisation in the nucleus. This is in agreement with other workers who have found that oestradiol-17beta is preferentially bound to a nuclear fraction of uterus. This system of cell culture of uterus proved very limited, and as a result all farther, experiments on the mechanism of oestrogen action were performed in vivo on whole animals. After administration of a single, dose of oestradiol or the synthetic oestrogen diethylstilboestrol the uterine content of the following parameters beg a to increase at the following times after hormone treatment; water 2 hr.; RNA, 7 hr.; peotein, 14 hr.; DNA, 28 hr. This the order that would be expected from current ideas of protein synthesis and cell division. The type of RNA synthesised over the early period of oestrogen action was analysed by chromatography on columns of kieselguhr coated with methylated albumin, This Method, which accounts for all the species of RNA, showed ,that the ai.at6 o synthesis of ribosomal RNA and transfer RNA were increased after hormonal stimulation but DNA-like RNA was not. One interpretation of these, results is that there is no increase in messenger RNA following oestrogen stimulation, Another and perhaps more plausible interpretation is that DNA-like RNA is a precursor of another form of messenger RWA which is eluted from the column with the ribosomal RNA fraction. This would mean that all the major species of RNA were increased after hormone stimulation. The rapid turnover rate of DNA-like RNA supports this latter interpretation. The change in rate of RNA synthesis was measured by the amounts of incorporation of labelled precursors into RNA. When changes in the specific activity of the ribonucleotide pool were taken into account it was found that the rate of synthesis of RNA did not increase until 5 to 6 hr. after administration of oestradiol. This is in agreement with the increased amount of RNA in the uterus about 7 hr. after hormone administration. It was found that 1.5- 2 hr. after hormone administration there was a 5 fold Increase in the transport of labelled RNA precursors into the uterus, and that this corresponded to a large increase in water uptake into the uterus. This explains the increased incorporation of precursors into RNA at this time which other workers in the field have interpreted as increases in RNA synthesis. Two sites of action of oestradiol on the uterus have been proposed. One site is located at the periphery of the cell causing an increased transport of water and small pre-cursor molecules into the uterus at 1.5-2 hr. after hormone. administration. The other site is located in the nucleus causing an increasing RNA synthesis about 5 - 6 hr after hormone administration.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Endocrinology
Date of Award: 1969
Depositing User: Enlighten Team
Unique ID: glathesis:1969-72725
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 11 Jun 2019 11:06

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