Hormonal Imbalance-Associated Oxidative Stress and Protective Benefits of Nutritional Antioxidants

Several medical conditions resulting from endocrine disorders including diabetes, male and female infertility, thyroid diseases, and adult growth hormone deficiency related to premature mortality or multi-hormonal deficiency in chronic heart failure, are closely associated with oxidative stress (OS) as a consequence of imbalance in redox homeostasis that leads to an increase in cellular reactive oxygen species (ROS). ROS being autocatalytic, non-specific, and having short half-lives, are considered good signaling molecules and are well known for their role in mediating both physiological and pathophysiological signal transduction. On the other hand, hormones are the signal inducers; therefore, their role in impacting each other’s actions is inevitable in endocrinopathies and reproduction. Many investigations have shown that ROS interferes with sperm parameters in men with idiopathic infertility. The intricate interplay between hormones and OS is beyond comprehending. OS elevates the level of ROS and may increase blood levels of norepinephrine and cortisol. In recent studies, these hormones have been shown to considerably enhance ROS and reactive nitrogen species (RNS) levels. In addition to causing cellular structural damage, they also stimulate the immune and inflammatory systems. While ROS production by mitochondrial P450 systems in steroidogenic cells appears to be an inevitable phenomenon, they are reported to directly impair male reproductive function by enhancing the effect of glucocorticoids in Leydig cells. Ghrelin, leptin, and insulin have their receptors on hypothalamic proopiomelanocortin (POMC) and agouti-regulated peptide/neuropeptide Y (AgRP/NPY) neurons, where they control food intake and energy metabolism by releasing ROS. Albeit some hormones such as melatonin, estrogen, insulin, and progesterone pose antioxidant activity, others like thyroid hormones, corticosteroids, and catecholamines promote OS. Several hormonal receptors, such as thyroid hormone receptor β1 (THRB1) and estrogen-related receptor α (ERRα), play important roles in mitochondrial activity. As mitochondria are the principal source of ROS production, their excess release impacts mitochondrial structure and function. All aerobic cells are bestowed with efficient antioxidant defense to neutralize the noxious effects of ROS by maintaining redox homeostasis. Therefore, antioxidant supplements have become a topic of discussion in recent years, especially when reported for treating endocrine disorders and as alternative therapies to improve conventional treatment. As chemopreventive medicines, antioxidants also have traditionally been widely researched for their ability to inhibit carcinogenesis and tumor growth along with hormone management. The reversal of high-grade intraepithelial neoplasia has been reported using hormonal treatment with anti-estrogens in breast carcinogenesis or anti-androgens in prostate carcinogenesis, as well as the use of vitamin C and its combination with vitamin E with encouraging clinical trial outcomes.

This research topic aims to provide an overview of what is currently known about the association between oxidative stress and endocrine disorders. Also, it will focus to explore the most recent perspectives on the role of antioxidants or oxidative stress and their management in diverse endocrine disorders, including cancer, and potential therapeutics methods.

This Research Topic strives to focus on the most current achievements in the field, spanning both basic and clinical aspects, and invites contributions of Original Research, Reviews, and Methods, which include but are not limited to the following:

• Hormones and redox signaling

• Mitochondria as targets of hormone action and the role of ROS

• Endocrinopathies and oxidative stress

• ROS, hypothalamus, and obesity

• ROS and reproduction (male & female)

• Multi-OMICS approaches to endocrinopathies

• Endocrine-disrupting chemicals, ROS, and Health

• ROS, hormonal regulation, and cancer

• Antioxidant therapeutics in endocrinopathies

• Clinical trials with dietary antioxidant supplementation