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Title: Inhibins in normal and Down's Syndrome pregnancies
Author: Wallace, Euan Morrison
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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This thesis describes a series of clinical and laboratory studies examining the value of inhibins as novel prenatal markers of Down's syndrome. Inhibins are a family of glycoprotein proteins identified in gonadal tissue but known to be secreted by the placenta in pregnancy. The ontogeny of inhibin secretion in early pregnancy is described in detail comparing various pregnancy compartments in both normal and Down's syndrome pregnancies. It is shown that maternal serum levels of inhibin-A, one of two possible full processed inhibin dimers, are significantly elevated in Down's syndrome in both the first and second trimesters of pregnancy. Furthermore, mathematical modelling studies with other established prenatal markers (maternal age, human chorionic gonadotrophin and alpha fetoprotein) suggests that inhibin-A could increase second trimester detection rates by as much as 20%. Studies on amniotic fluid revealed that, unlike maternal serum in which only inhibin-A is detectable, both dimers, inhibin-A and inhibin-B, were present raising the possibility that the fetal membranes secrete significant amounts of inhibin. The lack of relationship between inhibin-A levels in paired serum and amniotic fluid samples supported this hypothesis, representing a significant re-appraisal of the previous understanding of inhibin biology in pregnancy. Studies of the amniotic fluid inhibin levels in Down's syndrome showed that inhibin-A levels are significantly lower than normal, the opposite of serum. This suggests that the fetal membranes not only secrete different inhibins from the placenta but that the secretion is differentially controlled. These studies have therefore described, in detail, the biology of specific inhibin forms in normal and aneuploid pregnancy demonstrating inhibin-A to be the second most valuable serum marker of Down's syndrome. Novel insights into normal placental endocrinology have also been afforded by the studies with the promise of new initiatives in Down's syndrome screening and conditions with related endocrinology.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available