Neurotensin Regulates Primate Ovulation Via Multiple Neurotensin Receptors
Andrew C Pearson1, Jessica S Miller1, Hannah J Jensen1
1Department of Basic and Translational Sciences, Eastern Virginia Medical School, Old Dominion University, Norfolk, VA 23501, USA.
Endocrinology
|March 4, 2025
Summary
Neurotensin (NTS) receptor antagonists NTSR1 and SORT1 block ovulation by disrupting follicle rupture, luteinization, and blood vessel formation in primate ovaries.
Area of Science:
- Reproductive Biology
- Endocrinology
- Molecular Medicine
Background:
- Neurotensin (NTS) is a neuropeptide involved in ovulation.
- NTS mRNA is expressed by granulosa cells, and its receptors are in ovulatory follicles.
Purpose of the Study:
- To investigate the roles of NTS receptors NTSR1 and SORT1 in primate ovulation in vivo.
- To determine the effects of specific antagonists on ovulatory events.
Main Methods:
- Cynomolgus macaque dominant follicles were injected with NTS receptor antagonists (SR142948, SR48692, AF38469) or vehicle control.
- hCG was administered to induce ovulation.
- Follicles were analyzed histologically for rupture, vascularization, and luteinization.
- In vitro studies assessed NTS effects on ovarian microvascular endothelial cell (mOMEC) migration and permeability.
Main Results:
- NTS receptor antagonists reduced or abolished follicle rupture.
- Antagonist treatment led to increased red blood cell extravasation and impaired capillary formation.
- Luteinization of granulosa cells was reduced in antagonist-treated follicles.
- In vitro, NTS promoted mOMEC migration and decreased permeability, effects blocked by NTSR1 or SORT1 antagonists/siRNA.
Conclusions:
- Both NTSR1 and SORT1 are critical for NTS-mediated ovulation, luteinization, and angiogenesis.
- Targeting these receptors may offer new strategies for ovulation control.
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