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Title: Steroid pre-receptor signalling in human endometrium
Author: McDonald, Sarah E.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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This work has shown that 11βHSD-1 mRNA is present at highest levels in the menstrual phase of the cycle and in first trimester deciduas, the times when an inflammatory response is evident. 11βHSD-2 mRNA and protein are present at all stages of the cycle, and also in first trimester deciduas. GR mRNA and protein are highly expressed throughout the cycle. MR mRNA expression varies across the cycle in a pattern similar to progesterone expression. 11βHSD-1 mRNA expression is increased in response to IL-1α and cortisol, and GR mRNA shows a similar trend. 11βHSD-1 and MR expression are not altered by IL-1α or cortisol.3βHSD-1 mRNA has been shown to be present only in first trimester deciduas; 3βHSD-1 is not detectable by these methods. Immunohistochemistry using an antibody which detects both 3βHSD-1 and -2 has shown low levels of protein in the tissues studied. AKR1C1-3 mRNAs are expressed throughout the menstrual cycle; all three enzymes are predominantly expressed in the secretory phase. AKR1C3 is localised to the glandular and surface epithelial cells, and vascular endothelium. AKR1C4 mRNA is not detectable in the endometrium at any stage of the menstrual cycle. Expression of steroid-metabolising enzymes is perturbed in the endometrium of users of a Levonorgestrel intra-uterine system, and also the following GnRH antagonist treatment for sub-fertility. These studies have shown that the endometrium has the ability to precisely regulate its balance of steroid hormone availability at a local level, and that this balance may be altered following administration of exogenous steroids. Further functional studies such as knockout or knockdown of these enzymes would expand this knowledge and fully elucidate steroid hormone metabolism and pre-receptor signalling.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available