Leptin, the product of the obese (ob) gene, is a potential regulator of development in primate gestation. During pregnancy, maternal serum leptin levels increase prior to changes in body mass and decline rapidly post-delivery, indicating that factors other than adiposity regulate leptin biosynthesis. Therefore, it is hypothesized that maternal hyperleptinemia may be due to enhanced leptin production by adipose tissue under the influence of elevated estrogen levels inherent to primate pregnancy We utilized the baboon (Papio anubis/cynocephalus ), an established model for the study of human pregnancy, to examine the effects of estrogen on leptin biosynthesis during primate pregnancy. Maternal serum leptin levels were highly elevated during pregnancy (P < 0.01) and increased with advancing gestation (P < 0.005). Ob mRNA transcripts and leptin were expressed in placenta and two types of maternal adipose tissue, and both were modulated by estrogen. Thus, leptin production was higher in pregnancy (P < 0.02) and increased with advancing gestation (P < 0.04) in adipose tissue. Conversely, placental ob mRNA transcripts declined from early to late gestation (P < 0.02). Effects were reversed by estrogen withdrawal, as ob mRNA and leptin were higher in placental villous tissue and lower (P < 0.05) in adipose tissue in fetectomized baboons. However, maternal leptin levels were unchanged in fetectomized baboons, suggesting that non-estrogen dependent mechanisms have the potential for maintaining serum levels To examine the molecular mechanism of estrogen action on leptin biosynthesis, in vitro reporter gene assays were employed. MCF-7 breast cancer or JEG-3 choriocarcinoma cells were transfected with a leptin-luciferase construct and treated with estradiol. Although estradiol did not stimulate activity in MCF-7 cells, leptin-luciferase was stimulated by estradiol (P < 0.05) in JEG-3 cells co-transfected with estrogen receptor alpha. Intriguingly, anti-estrogens stimulated leptin-luciferase activity (P < 0.05) in JEG-3 cells co-transfected with estrogen receptor beta, implying that ob promoter activation may be cell specific and dependent upon estrogen receptor expression Results suggest that estrogen modulates leptin biosynthesis in a tissue-specific manner via transcriptional and post-transcriptional mechanisms. Furthermore, results indicate that activation of the ob promoter is cell-specific and dependent upon estrogen receptor expression. Collectively, results suggest that estrogen is a permissive regulator of leptin biosynthesis and that non-estrogen dependent mechanisms and the interplay between leptin and other gestational hormones may be imperative to the regulation of leptin biosynthesis during primate pregnancy / acase@tulane.edu
| Identifer | oai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_27326 |
| Date | January 2000 |
| Contributors | O'Neil, Jennifer Alice Snyder (Author), Henson, Michael C (Thesis advisor) |
| Publisher | Tulane University |
| Source Sets | Tulane University |
| Language | English |
| Detected Language | English |
| Rights | Access requires a license to the Dissertations and Theses (ProQuest) database., Copyright is in accordance with U.S. Copyright law |
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