2. Academic Validation
  3. LH promotes testosterone synthesis in rooster leydig cells through YAP1/ACSL4/SOAT1 pathway

LH promotes testosterone synthesis in rooster leydig cells through YAP1/ACSL4/SOAT1 pathway

  • Theriogenology. 2026 Apr 1:254:117813. doi: 10.1016/j.theriogenology.2026.117813.
Ziming Wang 1,  Jingxin Pu 1,  Wen An 1,  Chunqi Hou 1,  Qiuju Zheng 1,  Jing Zhao 1,  Xin Ma 1,  Yi Fang 1,  Hongyu Liu 1,  Jing Guo 1,  He Ding 1,  Yang Lyu 1,  Jun Wang 2,  Wenfa Lyu 3
Affiliations

Affiliations

  • 1 College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, Jilin Province, China; Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, 130118, Jilin Province, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, 130118, Jilin Province, China.
  • 2 College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, Jilin Province, China; Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, 130118, Jilin Province, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, 130118, Jilin Province, China. Electronic address: [email protected].
  • 3 College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, Jilin Province, China; Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun, 130118, Jilin Province, China; Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun, 130118, Jilin Province, China. Electronic address: [email protected].
PMID: 41529502 DOI: 10.1016/j.theriogenology.2026.117813
Abstract

Testosterone synthesis in Leydig cells requires precise coordination between LH signaling and Cholesterol metabolism, but the mechanisms underlying this regulation remain incompletely understood. In this study, we reveal a previously unrecognized YAP1-ACSL4 axis essential for LH-induced testosterone production by integrating transcriptomic profiling and functional studies in Leydig cells. Transcriptomic Sequencing identified ACSL4 and YAP1 as key regulators of testosterone synthesis induced by LH. The inhibition of YAP1 led to the downregulation of ACSL4 expression, which significantly reduced testosterone production. Similarly, si-ACSL4 directly reduced testosterone production in Leydig cells. Notably, transcriptomic Sequencing after interfering with ACSL4 showed that SOAT1 is a key molecule downstream of ACSL4. SOAT1 promoted testosterone synthesis by inhibiting esterification of free Cholesterol and subsequently increasing Cholesterol availability providing Materials for testosterone synthesis. Mechanistically, ACSL4 modulates Cholesterol availability through SOAT1 suppression, shifting metabolic flux from Cholesterol ester storage toward Cholesterol. These results indicate that LH promotes testosterone synthesis by upregulating YAP1 expression, which in turn increases ACSL4 expression, inhibits SOAT1 expression, and raises the concentration of free Cholesterol. This finding provides the first evidence linking ACSL4-mediated lipid metabolism to gonadotropin-regulated steroidogenesis.

Keywords

ACSL4; LH; Leydig cells; SOAT1; Testosterone; YAP1.

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