Sphingosine-1-phosphate regulation of luteinising hormone-induced steroidogenesis and proliferation of bovine theca cells in vitro
Zaire B. Medina-Moctezuma A § , Cyndi G. Hernández-Coronado B § , Lydia Marín-López C , Adrián Guzmán B , David González-Aretia A , Carlos G. Gutiérrez D and Ana Ma. Rosales-Torres
B *
+ Author Affiliations
- Author Affiliations
A Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Ciudad de México, México.
B Departamento Producción Agrícola y Animal, Universidad Autónoma Metropolitana-Xochimilco, Ciudad de México 04960, México.
C Maestría en Ciencias de la Producción y de la Salud Animal, Universidad Nacional Autónoma de México, Ciudad de México 04510, México.
D Departamento de Reproducción, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad de México 04510, México.
* Correspondence to: anamexico@gmail.com, anamaria@correo.xoc.uam.mx
Handling Editor: Geraldine Hartshorne
Reproduction, Fertility and Development 35(9) 518-526 https://doi.org/10.1071/RD22289
Published online: 25 May 2023
© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing
Abstract
Context: Sphingosine-1-phosphate (S1P) is synthesised by follicle granulosa cells under the influence of follicle-stimulating hormone and seems to be necessary for the biological effects of this gonadotrophin.
Aims: To determine if luteinising hormone (LH) increases S1P production and if this sphingolipid, either induced by LH or added to culture media, regulates steroidogenesis and cell viability in bovine theca cells.
Methods: We used bovine theca cell cultures treated with: S1P (0, 0.1, 1 and 10 μM; Experiment 1), LH (0, 0.02, 0.2 and 2 ng mL−1; Experiment 2) and LH (0.02 ng mL−1) plus a sphingosine kinase inhibitor (SKI-178; 0, 5 and 10 μM; Experiment 3).
Key results: Treatment with S1P did not affect (P > 0.05) theca cell viability or their ability to produce progesterone and testosterone. LH (0.02 ng mL−1) increased (P < 0.05) S1P production, and stimulated the expression of phosphorylated sphingosine kinase-1 (pSPHK1). However, the inhibition of SPHK1, by a specific SPHK1 inhibitor (SKI-178), reduced (P < 0.05) cell viability and progesterone secretion. Additionally, the use of SKI-178 increased theca cell testosterone production (P < 0.05).
Conclusions: S1P added to culture media did not affect cell viability or steroid synthesis. However, LH stimulated the production of S1P, by increasing phosphorylation of SPHK1 in theca cells. This intracellular S1P was inhibitory on testosterone production but augmented progesterone and viable cell number.
Implications: These results suggest a novel signalling pathway for LH in theca cells and underline the importance of S1P in the regulation of steroid synthesis.
Keywords: bovine follicles, cell viability, luteinising hormone, progesterone, sphingosine-1-phosphate, SPHK1, testosterone, theca cells.
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