ORCID
0000-0002-7112-5164 (Sage), 0000-0001-9345-2740 (Duffy)
Document Type
Article
Publication Date
2025
DOI
10.1093/biolre/ioaf218
Publication Title
Biology of Reproduction
Volume
Advance online publication
Pages
ioaf218 (1-16)
Abstract
Theca cells are a critical steroidogenic cell type of the ovarian follicle and corpus luteum. The ovulatory luteinizing hormone (LH) surge (or human chorionic gonadotropin (hCG)) stimulates theca cell relocation from the stroma surrounding the dominant follicle to full integration into the developing corpus luteum. Luteinizing hormone/human chorionic gonadotropin also stimulates granulosa cells to produce local mediators of ovulation, including the peptide neurotensin (NTS). To determine if hCG-stimulated NTS regulates theca cell relocation within the ovulatory follicle, vehicle or an NTS receptor antagonist was injected into a macaque dominant follicle, and ovaries were removed 48 h after hCG administration. Additional ovaries with dominant follicles were collected without administration of hCG (pre-hCG). Theca cells were sparse in the ovarian stroma surrounding pre-hCG follicles, while theca cells were abundant in the stroma and granulosa cell layer of recently-ovulated, hCG-treated follicles. Intrafollicular injection of a general NTS receptor antagonist or antagonist selective for a specific NTS receptor (NTSR1 or SORT1) reduced theca migration into the granulosa cell layer after hCG. In vitro, NTS stimulated macaque theca cell migration in conventional and 3-dimensional migration assays, and NTS receptor antagonists blocked NTS-stimulated migration. Neurotensin-stimulated theca cell migration in vitro was influenced by ovarian extracellular matrix components, with laminin reducing theca cell migration. NTS also increased theca cell number in vivo and stimulated theca cell proliferation in vitro. In summary, hCG-stimulated NTS acts directly at theca cells via NTSR1 and SORT1 to stimulate theca cell migration during ovulation and transformation of the ovulatory follicle into the corpus luteum.
Rights
© The Authors 2025.
This is an Open Access Article Distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) License, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited
Data Availability
Article states: "All data are included in the manuscript."
Original Publication Citation
Miller, J. S., Sage, M. A. G., Curry, T. E., Jr., & Duffy, D. M. (2025). Neurotensin drives theca cell migration during ovulation in primates. Biology of Reproduction. Advance online publication. https://doi.org/10.1093/biolre/ioaf218
Repository Citation
Miller, J. S., Sage, M. A. G., Curry, T. E., Jr., & Duffy, D. M. (2025). Neurotensin drives theca cell migration during ovulation in primates. Biology of Reproduction. Advance online publication. https://doi.org/10.1093/biolre/ioaf218
Supplementary data- jpeg file
migration_laminin_dose_response_diane_ioaf218.pdf (193 kB)
Supplementary data-jpeg file
supplemental_figure_legends_ioaf218.pdf (118 kB)
Supplemental data-docx file
Included in
Cells Commons, Obstetrics and Gynecology Commons, Urogenital System Commons, Women's Health Commons