Androgen synthesis cell‐specific CREBZF deficiency alters adrenal cortex steroid secretion and develops behavioral abnormalities in adult male mice

• DOI: 10.1096/fj.202400130r
• Publication Date: 2024-05-02T15:44:23Z
• Authors: Hongyu Niu; Chao Li; Hexin Zhang; Haokun Liu; Chunmei Shang; Yanni Jia; Wuenjiya; Zuhui Li; Aihua Wang; Yaping Jin; Pengfei Lin
• Keywords: Corticosterone; Zona reticularis; Sex steroid

Abstract The global challenge of male infertility is escalating, notably due to the decreased testosterone (T) synthesis in testicular Leydig cells under stress, underscoring critical need for a more profound understanding its regulatory mechanisms. CREBZF, novel basic region‐leucine zipper transcription factor, regulates mouse vitro; however, further validation through vivo experiments essential. Our study utilized Cyp17a1‐Cre knock out CREBZF androgen‐synthesis and explored physiological roles fertility, steroid hormone synthesis, behaviors adult mice. Conditional knockout (cKO) did not affect fertility serum level Primary isolated from CREBZF‐cKO mice showed impaired secretion mRNA levels Star , Cyp17a1 Hsd3b1 . Loss resulted thickening adrenal cortex, especially X‐zone, with elevated corticosterone dehydroepiandrosterone sulfate levels. Immunohistochemical staining revealed increased expression StAR, Cyp11a1, 17β‐Hsd3 cortex mice, while AR was significantly reduced. Along histological changes abnormal gland, higher anxiety‐like behavior memory plus maze Barnes maze, respectively. In summary, dispensable deficiency promotes function These results shed light on requirement stress response contribute crosstalk between testes glands.