Association of Increased SOAT2 Expression with Abnormal Cholesterol Esterification and Testosterone Deficiency in Late-Onset Hypogonadism Rats.

BACKGROUND

Late-Onset Hypogonadism (LOH) is a prevalent age-related condition in men, characterized by a decline in testosterone (T) and associated symptoms.

OBJECTIVE

This study explored the mechanism of T deficiency in LOH.

METHODS

Male SD rats were raised until 20 months of age in order to establish the LOH models. The hormone level and sperm quality were examined. The behavior experiments were carried out to assess whether LOH rats had anxiety and cognitive dysfunction. RNA-seq was used to explore the differential gene in the testis of LOH rats, revealing the molecular mechanism of LOH.

RESULTS

LOH rats exhibited cognitive impairment and anxiety. The sperm quality was decreased, and dysfunction of the Hypothalamic-Pituitary-Gonadal (HPG) axis was observed in LOH rats. Testosterone biosynthesis enzymes (including StAR, Cyp17A1, and HSD17β) were suppressed, reducing T levels. RNA-seq revealed that cholesterol metabolism and steroid hormone biosynthesis were abnormal. The expression of Sterol O-Acyltransferase 2 (SOAT2) was upregulated in the Leydig cells in the testes of LOH rats. Meanwhile, the testicular Cholesterol Ester (CE) increased, and Free Cholesterol (FC) decreased in the LOH rats.

DISCUSSION: These results indicated that upregulation of SOAT2 decreased FC and increased CE, which led to testosterone deficiency and further affected spermatogenesis and the HPG axis.