Abstract
Context: Luteal progesterone is fundamental for reproduction, but the molecular regulation of the corpus luteum (CL) in women remains unclear. Galectin-1 and galectin-3 bind to the sugar chains on cells to control key biological processes including cell function and fate.
Methods: The expression and localization of LGALS1 and LGALS3 were analyzed by quantitative PCR and histochemical analysis, with special reference to alpha 2,6-sialylation of glycoconjugates in carefully dated human CL collected across the menstrual cycle and after exposure to human chorionic gonadotrophin (hCG) in vivo. The effects of hCG and prostaglandin E-2 on the expression of galectins and an alpha 2,6-sialyltransferase 1 (ST6GAL1) in granulosa lutein cells were analyzed in vitro.
Results: Galectin-1 was predominantly localized to healthy granulosa lutein cells and galectin-3 was localized to macrophages and regressing granulosa lutein cells. Acute exposure to luteotrophic hormones (hCG and prostaglandin E2) up-regulated LGALS1 expression (P <.001). ST6GAL1, which catalyzes alpha 2,6-sialylation to block galectin-1 binding, increased during luteolysis (P <.05) as did LGALS3 (P <.05). Luteotrophic hormones reduced ST6GAL1 and LGALS3 in vivo (P <.05) and in vitro (P <.001). There was an inverse correlation between the expression of ST6GAL1 and HSD3B1 (P <.01) and a distinct cellular relationship among alpha 2,6-sialylation, 3 beta-hydroxysteroid dehydrogenase, and galectin expression.
Conclusions: Galectin-1 is a luteotrophic factor whose binding is inhibited by alpha 2,6-sialylation in the human CL during luteolysis. ST6GAL1 and galectin-3 expression is increased during luteolysis and associated with a loss of progesterone synthesis. Luteotrophic hormones differentially regulate galectin-1 and galectin-3/alpha 2,6-sialylation in granulosa lutein cells, suggesting a novel galectin switch regulated by luteotrophic stimuli during luteolysis and luteal rescue.
Original language | English |
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Pages (from-to) | 4616-4624 |
Number of pages | 9 |
Journal | The Journal of Clinical Endocrinology & Metabolism (JCEM) |
Volume | 99 |
Issue number | 12 |
Early online date | 15 Sept 2014 |
DOIs | |
Publication status | Published - Dec 2014 |
Keywords / Materials (for Non-textual outputs)
- CORPUS-LUTEUM
- DEATH RECEPTOR
- APOPTOSIS
- BINDING
- RECOGNITION
- LUTEOLYSIS
- EXPRESSION
- LOCALIZATION
- SIALYLATION
- PREGNANCY
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Colin Duncan
- Deanery of Clinical Sciences - Personal Chair of Reproductive Medicine and Science
- Edinburgh Imaging
- Centre for Reproductive Health
Person: Academic: Research Active