Fig. 3: Hierarchical regulation of testosterone synthesis in the male hypothalamic-pituitary-gonadal (HPG) axis.
From: The testobolome in microbial testosterone metabolism and human health
Specialized neurons initiate the axis by releasing kisspeptin, which binds to KISS1R on gonadotropin-releasing hormone (GnRH) neurons166,167. This stimulates pulsatile GnRH secretion, which triggers the anterior pituitary to produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH) that promote steroidogenesis in the gonads. LH stimulates Leydig cells in the testes to produce testosterone through a multi-step steroidogenic process: cholesterol is imported into mitochondria via steroidogenic acute regulatory protein (StAR) and converted to pregnenolone by cholesterol desmolase CYP11A1168. Subsequent enzymatic steps, primarily via the CYP17A1, 3β-HSD, and 17β-HSD enzymes (Fig. 2), yield testosterone, which is secreted into circulation and also acts locally within the testes to support spermatogenesis. Figure created with BioRender.
