Granulosa cell function in domestic animals: A review on the in vitro effects of FSH, insulin and insulin-like growth factor 1.
Abstract: Ovarian granulosa cells produce a variety of biologically active compounds in addition to steroid hormones that include numerous families of growth factors, cytokines and adipokines. Many of these function as endocrine, paracrine and autocrine hormones to regulate ovarian activity. The goal of this review is to provide an update on the evidence in domestic animals on how FSH, insulin and IGF1 regulate the function of granulosa cells with a focus on ovarian steroidogenesis and cell proliferation with comparisons across six domestic animals: pigs, cattle, horses, water buffalo, goats and sheep. In most species, FSH was not a mitogenic stimulus to granulosa cells whereas insulin and IGF1 were stimulatory to cell proliferation in the species it was evaluated. FSH, insulin and IGF1 were all stimulatory to granulosa cell steroidogenesis in the species it was studied. More research is needed to evaluate the role of insulin in the regulation of cell proliferation and steroidogenesis in water buffalo and goats. The role of IGF1 in regulating granulosa cell function in horses also needs further study. Most granulosa-cell secreted factors have direct effects (either positive or negative) on FSH-, insulin- and IGF1-induced steroid production in ovarian cells, but how they all work together to create a cumulative effect to regulate fertility will require further research.
Copyright © 2025 Elsevier Inc. All rights reserved.
Publication Date: 2025-01-23 PubMed ID: 39879874DOI: 10.1016/j.domaniend.2025.106919Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Review
Summary
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Overview
- This research article reviews how follicle-stimulating hormone (FSH), insulin, and insulin-like growth factor 1 (IGF1) influence the function of ovarian granulosa cells in domestic animals.
- The focus is on how these hormones affect granulosa cell steroid hormone production and cell proliferation across six species: pigs, cattle, horses, water buffalo, goats, and sheep.
Background on Granulosa Cells
- Granulosa cells line the ovarian follicles and play essential roles in reproduction by producing steroid hormones (e.g., estrogen and progesterone).
- Besides steroid hormones, they produce growth factors, cytokines, and adipokines—biologically active compounds that influence ovarian function.
- These secreted factors act through endocrine (bloodstream), paracrine (nearby cells), and autocrine (self-signaling) mechanisms.
- The complex interplay of these molecules helps regulate follicle development, ovulation, and fertility.
Hormonal Regulation: FSH, Insulin, and IGF1
- FSH (Follicle stimulating hormone): A key hormone stimulating ovarian follicle growth and estrogen production.
- Insulin: A metabolic hormone that also influences ovarian function by regulating cell growth and steroid synthesis.
- IGF1 (Insulin-like growth factor 1): A growth factor that has important roles in cell proliferation and differentiation, including within ovarian follicles.
Findings on Cell Proliferation
- In most studied species, FSH alone does not stimulate granulosa cell proliferation (i.e., it is not mitogenic).
- In contrast, insulin and IGF1 generally promote granulosa cell proliferation across species where this was assessed.
- This indicates that metabolic and growth factors may be more influential than FSH in driving granulosa cell multiplication.
- Specific data gaps exist, especially regarding insulin’s role in water buffalo and goats.
Findings on Steroidogenesis (Hormone Production)
- All three hormones—FSH, insulin, and IGF1—stimulate steroid hormone production by granulosa cells across species where investigated.
- This suggests cooperative roles in promoting estrogen and other steroid synthesis necessary for follicle maturation and reproductive function.
- Clarification is needed on IGF1’s influence in horses, as current research is limited.
Interactions with Granulosa Cell Secreted Factors
- Granulosa cells secrete many biologically active substances that can modulate the effects of FSH, insulin, and IGF1.
- These secreted factors may enhance or inhibit steroid production induced by the three hormones.
- The combined, cumulative impact of these factors on ovarian function and fertility is complex and not fully understood.
- Further research is needed to unravel how these numerous signals integrate to ultimately regulate female fertility in various domestic species.
Gaps and Future Directions
- More research is needed to better understand insulin’s role in regulating granulosa cell proliferation and steroidogenesis in water buffalo and goats.
- The role of IGF1 in horse granulosa cell function remains underexplored and requires deeper study.
- Investigations into interactions among granulosa cell secreted factors and hormones will be key to fully deciphering ovarian regulation mechanisms.
- Such insights can inform reproductive management and improve fertility in domestic animal species.
Cite This Article
APA
Spicer LJ, Maylem ERS, Schütz LF.
(2025).
Granulosa cell function in domestic animals: A review on the in vitro effects of FSH, insulin and insulin-like growth factor 1.
Domest Anim Endocrinol, 91, 106919.
https://doi.org/10.1016/j.domaniend.2025.106919 Publication
Researcher Affiliations
- Department of Animal and Food Sciences, Oklahoma State University, Stillwater, OK 74078 USA. Electronic address: leon.spicer@okstate.edu.
- Philippine Carabao Center, National Headquarters and Gene Pool, Science City of Munoz, Nueva Ecija, Philippines.
- Department of Agriculture, Veterinary & Rangeland Sciences, University of Nevada, Reno, NV, 89557 USA.
MeSH Terms
- Animals
- Granulosa Cells / physiology
- Granulosa Cells / drug effects
- Insulin-Like Growth Factor I / pharmacology
- Female
- Follicle Stimulating Hormone / pharmacology
- Insulin / pharmacology
- Animals, Domestic / physiology
- Cell Proliferation
- Insulin-Like Peptides
Citations
This article has been cited 1 times.- Hayashi K, MacLean JA 2nd. RHOX Homeobox Transcription Factor Regulation of Ins2 in Rodent Granulosa Cells.. Cells 2025 Mar 22;14(7).
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