Stress Induced Cortisol Release Depresses The Secretion of Testosterone in Patients With Type 2 Diabetes Mellitus

Abstract

Background: Both hormonal and genetic data reveal that the stress hormone cortisol and its regulating genes may affect the level of testosterone in humans. It is uncertain whether type 2 diabetes mellitus would manifest similarly. Furthermore, a genetic strategy to screen out the stress system genes that may contribute to testosterone decline in humans is less understood. Objectives: In this study, we aimed to elucidate the link between stress and testosterone levels, both hormonally and genetically. Method: This study comprised 37 individuals with type 2 diabetes mellitus and 50 healthy individuals. For the analysis of hormones and the targeted genes, we used the RIA system and bioinformatics expertise. Results: The patients had significantly elevated cortisol and lower testosterone readings, according to data from hormonal analyses. The bioinformatics approach reveals that SHBG was intracellularly suppressed by 2 defined stress system genes: FKB5 and CYP17. TCF4/TCF8, ATRX, and AR in skeletal muscle were inversely related to stress system genes. Furthermore, all testosterone regulated genes were positively linked with SHBG in the current study. A strong relationship between GNAS and PKA with CYP17 and FKBP5 reveals that the Gαs-cAMP/PKA signaling pathway may be one of the regulatory pathways through which the suppression of testosterone system genes happens. In conclusion, this study demonstrated that beyond stress, the key stress system genes might affect cortisol levels, which in turn affect testosterone figures via the Gαs-cAMP/PKA signaling pathway.

The Metabolic Syndrome, a Human Disease

“…An important aspect of corticosteroids is their regulation of blood vessel reactivity, affecting blood flow and pressure [203,216], largely in contraposition to DHEA (dehydroepiandrosterone) [217,218]; interacting with T (and other androgens), E2 [110,188,219], and insulin [220,221]; and even acting in coordination with catecholamines [222,223]. Corticosteroids also show a critical effect on behavior, in conjunction with other steroid hormones [224,225], including appetite (via a myriad of additional cytokines, non-coding RNAs, and other protein factors). The relationship with neural transmission and the modulation of the complex nature of depression has been also acknowledged, but the mechanisms have not yet been fully established [226][227][228].…”

Exploring the influence of stress on aggressive behavior and sexual function: Role of neuromodulator pathways and epigenetics

“…Additionally, research has highlighted the role of stress-related hormones, such as cortisol, in modulating the physiology of the androgen system. Elevated cortisol levels, commonly observed during stress, have been associated with reduced testosterone levels and altered androgen signaling pathways [ 106 , 107 ]. However, a study found that testosterone levels increased after acute stress exposure in all groups, regardless of borderline personality disorder (BPD) or posttraumatic stress disorder (PTSD) status, suggesting that stress-related changes in testosterone release are not influenced by these disorders in young adult men [ 108 ].…”