| First Author | Maqdasy S | Year | 2015 |
| Journal | Endocrinology | Volume | 156 |
| Issue | 12 | Pages | 4545-57 |
| PubMed ID | 26402841 | Mgi Jnum | J:232749 |
| Mgi Id | MGI:5780021 | Doi | 10.1210/en.2015-1382 |
| Citation | Maqdasy S, et al. (2015) Identification of the Functions of Liver X Receptor-beta in Sertoli Cells Using a Targeted Expression-Rescue Model. Endocrinology 156(12):4545-57 |
| abstractText | Liver X receptors (LXRs) are key regulators of lipid homeostasis and are involved in multiple testicular functions. The Lxralpha(-/-);Lxrbeta(-/-) mice have illuminated the roles of both isoforms in maintenance of the epithelium in the seminiferous tubules, spermatogenesis, and T production. The requirement for LXRbeta in Sertoli cells have been emphasized by early abnormal cholesteryl ester accumulation in the Lxrbeta(-/-) and Lxralpha(-/-);Lxrbeta(-/-) mice. Other phenotypes, such as germ cell loss and hypogonadism, occur later in life in the Lxralpha(-/-);Lxrbeta(-/-) mice. Thus, LXRbeta expression in Sertoli cells seems to be essential for normal testicular physiology. To decipher the roles of LXRbeta within the Sertoli cells, we generated Lxralpha(-/-);Lxrbeta(-/-):AMH-Lxrbeta transgenic mice, which reexpress Lxrbeta in Sertoli cells in the context of Lxralpha(-/-);Lxrbeta(-/-) mice. In addition to lipid homeostasis, LXRbeta is necessary for maintaining the blood-testis barrier and the integrity of the germ cell epithelium. LXRbeta is also implicated in the paracrine action of Sertoli cells on Leydig cells to modulate T synthesis. The Lxralpha(-/-);Lxrbeta(-/-) and Lxralpha(-/-);Lxrbeta(-/-):AMH-Lxrbeta mice exhibit lipid accumulation in germ cells after the Abcg8 down-regulation, suggesting an intricate LXRbeta-dependent cooperation between the Sertoli cells and germ cells to ensure spermiogenesis. Further analysis revealed also peritubular smooth muscle defects (abnormal lipid accumulation and disorganized smooth muscle actin) and spermatozoa stagnation in the seminiferous tubules. Together the present work elucidates specific roles of LXRbeta in Sertoli cell physiology in vivo beyond lipid homeostasis. |
