Neurotensin drives theca cell migration during ovulation in primates†.

Area of Science:

• Reproductive Biology
• Endocrinology
• Cell Biology

Background:

• Theca cells are crucial for ovarian steroidogenesis and follicle development.
• Ovulation involves the coordinated migration of theca cells into the granulosa layer, a process influenced by hormonal surges like luteinizing hormone (LH) or human chorionic gonadotropin (hCG).
• Neurotensin (NTS) is a peptide mediator produced by granulosa cells following hCG stimulation, potentially regulating ovulation-related events.

Purpose of the Study:

• To investigate the role of hCG-stimulated NTS in regulating theca cell relocation during ovulation.
• To determine if NTS directly influences theca cell migration and proliferation.
• To identify the specific NTS receptors involved in mediating these effects on theca cells.

Main Methods:

• Ovarian follicles from macaques were analyzed before and after hCG administration.
• Intrafollicular injections of NTS receptor antagonists were administered to assess their impact on theca cell migration in vivo.
• Theca cell migration and proliferation were evaluated in vitro using conventional and 3D assays.
• The influence of extracellular matrix components on NTS-stimulated theca cell migration was examined.

Main Results:

• HCG administration led to increased theca cell abundance in the granulosa cell layer and ovarian stroma.
• Inhibition of NTS receptors (general, NTSR1, or SORT1) significantly reduced theca cell migration into the granulosa layer post-hCG.
• NTS exposure in vitro stimulated macaque theca cell migration and proliferation.
• NTS-induced theca cell migration was modulated by ovarian extracellular matrix, with laminin showing an inhibitory effect.
• NTS receptor antagonists blocked NTS-stimulated theca cell migration in vitro.

Conclusions:

• HCG-stimulated NTS directly targets theca cells via NTSR1 and SORT1 to promote their migration during ovulation.
• NTS plays a critical role in the relocation of theca cells from the follicle periphery to the granulosa layer.
• These findings elucidate a novel signaling pathway regulating theca cell dynamics essential for the transformation of the ovulatory follicle into the corpus luteum.