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Bi-modal anti-Müllerian hormone signalling in the ovary.

48 months
Approved budget:
Dr Michael Pankhurst
Health issue:
Reproduction/fertility/sexual health
Proposal type:
Sir Charles Hercus Fellowship
Lay summary
Anti-Müllerian hormone (AMH) is an ovarian regulator of egg development and appears to contribute to conditions of infertility. Most of the AMH secreted in the ovary is inactive but my research has shown the majority is activated by the time it reaches circulation. This project will determine if extracellular activation of AMH is the key mechanism that enables it to signal at two distinct locations in the ovary. The active and inactive forms will be specifically quantified at multiple sites in the human ovary using microdialysis. Fluorescent biomarkers and multiphoton live-imaging will reveal the anatomical location(s) of the AMH-activating enzymes. Electron-microscopy will determine how the protein structure of AMH defines its bioactivity. Dysregulation of AMH affects fertility but its precise role in the ovary remains unclear. Elucidating the relevant signalling mechanisms will reveal potential therapeutic targets providing a platform for a career in translational fertility research and reproductive endocrinology.