The Origin of 7α-Hydroxy-Dehydroepiandrosterone and Its Physiological Role: a History of Discoveries

Abstract

Nearly 60 years has elapsed since the first isolation and identification of 7α-hydroxy-dehydroepiandrosterone, and in that time much information has been gained on its occurrence, metabolism, ontogeny, immunomodulatory activity, cell proliferation, cortisol control in local tissues and neuroactivity. Additional knowledge about this steroid may elucidate its role in obesity, neurodegenerative disturbances such as Alzheimer’s disease, or psychiatric disorders such as schizophrenia or depression. This review aims to provide a comprehensive summary of the available literature on 7α-hydroxy-dehydroepiandrosterone.

Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: A comprehensive review

“…DHEA, 16α-hydroxylation is the most frequent hydroxylation detected in adults followed by 7α-hydroxylation (Fig. 4(f)), while 16β-, 21-, 18- and 15β-hydroxylation are also observed in neonates [[133], [134], [135], [136]].…”

Cytochrome P450 Monooxygenases Catalyse Steroid Nucleus Hydroxylation with Regio‐ and Stereo‐Selectivity

“…Hydroxylation of steroids can strongly affect their biological activity, polarity, and toxicity. [3] Diverse positions and configurations of oxygen-containing functional groups often endow steroids with different pharmacological activities: for example, 7α-hydroxy-dehydroepiandrosterone (7α-hydroxy-DHEA) potentially promotes weight loss and boosts the activity of the immune system, [4] while 7β-hydroxy-DHEA is a neuroprotective, anti-inflammatory, and immunomodulatory agent. [5] All steroids contain a cyclopentane-hyper phenanthrene carbon skeleton (also called the steroid nucleus), which is predominated by sp 3 CÀ H bonds and lacks functional groups that can activate CÀ H bonds.…”

The catalytic activity of mycelial fungi towards 7‐oxo‐DHEA – an endogenous derivative of steroidal hormone dehydroepiandrosterone

“…As reported in the available scientific literature, 7‐oxo‐DHEA ( 1 ) metabolism in humans is mainly concerned with the reduction of C‐17 ketone by 17β‐hydroxysteroid dehydrogenase (17β‐HSD) generating 3β,17β‐dihydroxy‐androst‐5‐en‐7‐one ( 2 ) or/and reduction of the ketone at C‐7 position by 11β‐HSD1 leading to the formation of epimeric 7β‐ (mainly) and 7α‐ alcohols (7α‐ and 7β‐hydroxy‐DHEA ( 3 )), and their reduction to 3β,7α,17β‐ and 3β,7β,17β‐triols (3β,7α,17β‐trihydroxy‐androst‐5‐ene ( 4 ) and 3β,7β,17β‐trihydroxy‐androst‐5‐ene ( 5 )) (Nashev et al ., 2007). These metabolites are multifunctional compounds implicated in a broad range of biological processes, mainly attributed to immune system modulation, anti‐inflammatory, antiglucocorticoid and neuroprotective actions (El Kihel, 2012; Stárka, 2017; Stárka et al ., 2018). Changes in the ratio of 7α/7β‐hydroxy‐DHEA and both isomeric triols were detected in patients with various disorders including vascular and Alzheimer dementia (Stárka, 2017).…”

“…These metabolites are multifunctional compounds implicated in a broad range of biological processes, mainly attributed to immune system modulation, anti‐inflammatory, antiglucocorticoid and neuroprotective actions (El Kihel, 2012; Stárka, 2017; Stárka et al ., 2018). Changes in the ratio of 7α/7β‐hydroxy‐DHEA and both isomeric triols were detected in patients with various disorders including vascular and Alzheimer dementia (Stárka, 2017). The derivatives of 7‐oxo‐ or 7‐hydroxy‐DHEA with an additional 16α‐hydroxy group were isolated from urine of the patient with adrenal carcinoma (Pouzar et al ., 2005).…”