Date of Award

2002

Degree Type

Thesis

Degree Name

Bachelor of Science Honours

Faculty

Faculty of Communications, Health and Science

First Advisor

Dr Peter Roberts

Second Advisor

Dr Peter Burton

Abstract

Leptin is a 16kDa peptide hormone that has recently been implicated in human reproductive processes. Like other hormones, leptin exerts its influence through its receptor. Of the three major isoforms of the receptor (OB-Ra, OB-Rb, and 0B-Re), OB-Ra (the dominant short form) has been implicated in transport processes within rat and human placentas, suggesting a role for it in implantation and pregnancy maintenance. The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that are a subfamily of nuclear hormone receptors. PPARs form heterodimers with another nuclear hormone receptor, RXRα, before binding to PPAR response elements (PPREs). Recently PPARϒ/RXRα heterodimers have been implicated in trophoblast differentiation, thus playing a key role in human implantation and placentation. The present study used Western Blot analysis to quantify the presence of Ob-R and PPARϒ protein in human placental tissue from first and second trimesters, and at term (n=9, n=10, n=12 respectively). PPARϒ and OB-Ra were found at all stages of pregnancy. Levels of OB-Ra were significantly lower in second trimester than in first trimester or at term (p<0.01, one-way ANOVA). Interestingly, two different molecular weight (MW) protein bands of PPARϒ were found, one at ~55kDa and another at ~80kDa. The 80kDa PPARϒ protein decreased from first to second trimester and then increased to maximal levels at term (F=14.437, p<0.0001, one-way ANOVA), and the 55kDa PPARϒ protein was maximal in first trimester, fell in the second trimester, and remained at this level until term (F=3. 793394, p<0.05, one-way ANOVA). Furthermore, the 80kDa protein was greater than the 55kDa at all stages of pregnancy (first trimester p<0.005, second trimester p<0.0001, term p<0.0001). The presence of OB-Ra and PPARϒ over the three stages of human pregnancy demonstrates they are important in implantation and pregnancy maintenance, and this may aid in our understanding pathological conditions such as miscarriage and intrauterine growth retardation (IUGR).

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