Interactive metabolic signatures of testicular testosterone with bilateral adrenalectomy in mice

Abstract

The hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes have reciprocal relationships with steroidogenesis regulation. However, the relationship between testicular steroids and defec-tive glucocorticoid production under chronic stress remains unclear. Metabolic changes of testicular steroids in bilateral adrenalectomized (bADX) 8-week-old C57BL/6 male mice were measured using gas chromatography -mass spectrometry. Twelve weeks after surgery, testis samples were obtained from the model mice, which were divided into tap-water (n = 12) and 1 % saline (n = 24) supplementation groups, and their testicular steroid levels were compared with those of sham controls (n = 11). An increased survival rate with lower testicular levels of tetrahydro-11-deoxycorticosterone was observed in the 1 % saline group compared to both the tap -water (p = 0.029) and sham (p = 0.062) groups. Testicular corticosterone levels were significantly decreased in both tap-water (4.22 +/- 2.73 ng/g, p = 0.015) and 1 % saline (3.70 +/- 1.69, p = 0.002) groups compared to those in sham controls (7.41 +/- 7.39). Testicular testosterone levels tended to increase in both bADX groups compared to those in the sham controls. In addition, increased metabolic ratios of testosterone to androstene-dione in tap-water (2.24 +/- 0.44, p < 0.05) and 1 % saline (2.18 +/- 0.60, p < 0.05) mice compared to sham controls (1.87 +/- 0.55) suggested increased production of testicular testosterone. No significant differences in serum steroid levels were observed. Defective adrenal corticosterone secretion and increased testicular pro-duction in bADX models revealed an interactive mechanism underlying chronic stress. The present experimental evidence suggests the crosstalk between the HPA and HPG axes in homeostatic steroidogenesis.