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Title: Gene expression during fetal gonadal development
Author: Majdic, Gregor
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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In the first part of the thesis, temporal and spatial localisation of several different proteins has been studied using immunocytochemistry. Novel results regarding localisation of androgen receptor and inhibin subunits are reported which demonstrate differences in their patterns of expression in fetal and adult Leydig cells. Specifically, in contrast to their adult counterparts, fetal cells do not express androgen receptor, suggesting that the negative feedback loop of testosterone on its own production, established in adult testis via the androgen receptor, is not functional in the fetus. Inhibin α and βB subunits were localised to Leydig cells from days 14.5 and 16.5 of gestation respectively. In addition, functional differentiation of fetal Leydig cells has been studied by examining the expression of two steroidogenic enzymes 17α-hydroxylase/17,20-lyase (P450c17) and 3β-hydroxysteroid dehydrogenase (3β-HSD) and two orphan nuclear receptors, steroidogenic factor-1 (SF-1) and DAX-1. As expected 3β-HSD and P450c17 immunolocalised exclusively to fetal Leydig cells. Data on immunoexpression of DAX-1 has not been reported previously; DAX-1 protein was first detectable in the fetal rat testis on day 15.5 in the interstitial cells, simultaneously with the onset of testosterone production. Co-localisation of SF-1 and DAX-1 in the fetal testis demonstrated that both proteins are not exclusively co-localised in the same cell types, a finding at odds with suggestions that SF-1 regulates expression of DAX-1. The second part of the thesis describes experiments designed to elucidate potential mechanisms underlying the influence of oestrogens on the developing fetal testis. A significant decrease in mRNA expression and enzyme activity of P450c17 occurred in fetuses of mothers treated with DES or the environmental oestrogen octylphenol (OP) but this was not mirrored by an obvious reduction in 3β-HSD immunostaining.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available