The effect of oestradiol-17beta on RNA synthesis in the uterus of the immature rat

Knowler, John Terry (1972) The effect of oestradiol-17beta on RNA synthesis in the uterus of the immature rat. PhD thesis, University of Glasgow.

Abstract

1) The action of oestradiol at a molecular level, together with the current concepts of INA synthesis, maturation and transport are reviewed, IINA synthesis is investigated and characterized in the uterus of 18-21 day old rats responding to oestradiol-17beta. 2) The observed stimulation of RNA synthesis, in the uterus of rats treated with oestradiol-17beta is markedly dependent on the route of injection of precursor. After intraperitoneal administration of radioactive precursors, response is low and variable. Conversely, intravenous injection of precursor gives rise to a marked stimulation of RNA synthesis which is far in excess of the stimulated uptake into the acid-soluble pools and indicates that the increased uptake into RNA represents a real stimulation in RNA synthesis. Subcutaneous injection of precursor gives an intermediate response. 3) 18-21 day old rats respond maximally to a dose of 0.3?g/rat or more of oestradiol-17beta, the degree of response being dependent on the weight of the animals within the age range, 4) In vitro synthesis of ISIA, in uteri excised from oestrogen-treated rats, is only slightly stimulated and the increase can be accounted for by hormone-activated uptake of precursor. 5) The purification and separation of uterine RNA on polyacrylamide gels, agarose gels and sucrose density gradients is described. 6) The earliest detected effect of oestradiol is the stimulated synthesis of a very-high molecular weight RNA from approximately 30min after the administration of oestrndiol-17beta. The rapid synthesis and decay of this species, together with its nuclear location, absence of methylation and its base composition, permits its identification as heterogeneous nuclear RNA. The HnRNA made in response to oestradiol varies considerably in size. 7) Since evidence is accummulating that HnRNA contains polynucleotide sequences which ultimately become messengers, it is suggested that the stimulated production of this species in the uterus of oestrogen-treated rats may reflect hormone-induced rRNA synthesis and the translation of the messengers into protein may be a necessary prerequisite for stimulated rRNA synthesis and subsequent hormone augmented differentiation. 8) A striking change in the uteri of rats exposed to oestradiol is the stimulated synthesis of ribosomal RNA. When purified RNA is separated on 2.7% polyacrylamide gels, synthesis can he followed from the 45S precursor, through the 32S precursor and into the ribosomal submit species. Synthesis is first stimulated at, or shortly after, 1h of oestrogen treatment and is greatly increased 2 and 4h after hormone administration. Some evidence is presented that, in addition to increasing the rate of transcription of rRNA, oestradiol may also stimulate the rate of rRNA maturation together with its transport into the cytoplasm. 9) The fate of newly-synthesized ribosomes in oestrogen-treated uterine cells is investigated. As a consequence of hormone administration, pre-existing and newly-synthesized ribosomes appear to aggregate into polysomes but there are few membrane-bound ribosomes either before or after hormone treatment. The features of the induced production of ribosomes in immature rat uteri are discussed in relation to the current concepts of their involvement in hormone action. 10) Oestrogen-induced synthesis of tRNA may precede slightly the increase in rRNA synthesis, since the labelling of 45 RNA is clearly elevated 1h after hormone administration. Synthesis of both 45 and 55 RNA is strongly stimulated after 2 and 4h of oestrogen treatment. 11) The increased synthesis of rRNA in response to oestrodiol-17beta is acre strongly inhibited by actinomycin D than the synthesis of other RNA species. Cycloheximide, depending on the time of administration and dosage, inhibits either RNA synthesis or the maturation of rRNA.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: R MS Smellie
• Keywords: Endocrinology
• Date of Award: 1972
• Depositing User: Enlighten Team
• Unique ID: glathesis:1972-73252
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jun 2019 08:56
• Last Modified: 14 Jun 2019 08:56
• URI: https://theses.gla.ac.uk/id/eprint/73252