| 论文摘要： |
Chorionic gonadotropin alpha (Cg alpha) functions as the shared subunit for thyroid-stimulating hormone subunit f3 (Tshf3), luteinizing hormone subunit f3 (Lhf3), and follicle-stimulating hormone subunit f3 (Fshf3). While these f3-subunits have been extensively studied using effective gene knockout models in zebrafish, the biological role of Cg alpha remains elusive. In this study, cg alpha-deficient zebrafish generated via transcription activator-like effector nucleases (TALENs) exhibited viability but displayed pronounced developmental abnormalities, including growth retardation, hyperpigmentation, reduced thyroxine (T4) levels, and defective anterior swim bladder inflation during juvenile stages. In adults, cg alpha deficiency led to disrupted gonadal development, impaired secondary sex characteristics (SSCs), and severely impacted reproductive behavior in both female and male fish. Notably, both testicular and ovarian differentiation were observed in cg alpha-deficient fish and lh/3-/-;fsh/3-/- mutants. Gonadal sex differentiation in cg alpha-deficient zebrafish exhibited a pronounced shift toward testicular fate upon additional disruption of fsh/3 (cg alpha-/-;fsh/3-/-), marked by elevated anti-M & uuml;llerian hormone (amh) expression, or following loss of follicle-stimulating hormone receptor (fshr) (cg alpha-/-;fshr-/-). In vitro assays in Chinese hamster ovary (CHO) cells revealed increased cAMP response element (CRE) promoter activity following transfection with constructs encoding Fshr, Fshf3/Fshr, or Cg alpha/Fshf3/Fshr. Collectively, the phenotypes observed in cg alpha-deficient fish recapitulate those of thyrotropin-and gonadotropin-disrupted models, highlighting the essential role of Cg alpha in thyroid and gonadal function. Importantly, these findings uncover the role of Fsh signaling in maintaining proper ovarian differentiation in zebrafish, including Cg alpha-independent Fshf3 activity and the constitutive functionality of Fshr. |
