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Molecular Insights in Steroid Biosynthesis and Metabolism

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 2145

Special Issue Editor


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Guest Editor
Department of Biochemistry, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa
Interests: steroid biosynthesis and metabolism; biochemistry; molecular endocrinology; physiology; natural plant products

Special Issue Information

Dear Colleagues,

Steroid hormones are biosynthesized from cholesterol by the adrenal, gonads, placenta, and skin. In addition, steroid hormones are produced in the metabolism of precursor steroids in non-endocrine tissue such as the intestine, brain, kidneys, and adipose tissue, which express the appropriate steroidogenic enzymes. Since steroids play a pivotal role in normal physiology, steroid hormone dysfunction will be central to pathophysiology. Steroid hormone dysfunction has been associated with a host of clinical conditions linked to disorders due to deficient steroidogenic enzymes, the onset of Alzheimer’s, cancer, and kidney disease.

Steroid hormones have a central role within the endocrine system, controlling major physiological processes that include reproduction, sexual differentiation, growth, and development. Steroid hormones regulate cellular metabolism and energy balance while also maintaining nutrients, electrolyte, and water equilibrium in the blood. Steroids are also of important in the development and sexual differentiation of the brain. Besides having neuroprotective effects, these hormones influence cognition, stress, and memory performance. Steroid hormones also support the mobilization of the body’s defenses against stressors concerning inflammation and immunity. In regulating the innate immune response, steroids additionally influence the intestinal microbiota, with the microbiota in turn increasing inflammation by modulating steroid levels. Steroid hormones impact cardiovascular disease as do endogenous cardiac steroids, with endogenous ouabain influencing not only systemic blood pressure and heart functions but also kidney and brain functions.

The practice of hormone supplementation contributes either to the maintenance or to the disruption of the natural steroid hormone equilibrium. The supplementation of sex steroids includes hormone replacement therapies such as those replacing lost estrogen in menopause and testosterone supplementation in aging men. Within this context, anabolic steroids have far-reaching effects on the endocrine system, but their use or abuse continues regardless of these steroid derivatives contributing to disordered physiological processes and neurophysiological changes. 

The aim of this SI is to cover a wide range of topics and areas of interest. These include (but are not restricted to) the abovementioned aspects of steroidogenesis. Both original research and reviews will be considered.

Dr. Amanda C. Swart
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • steroid biosynthesis
  • steroid metabolism
  • aldo-keto reductase (AKR)
  • cytochrome P450
  • steroid reductase (SRD5A)
  • 17β-hydroxysteroid dehydrogenases (17βHSD)
  • 11β-hydroxysteroid dehydrogenase (11βHSD)
  • reproduction and sexual differentiation
  • endogenous cardiac steroids
  • anabolic steroids
  • prostate cancer
  • gut microbiome
  • immune system
  • inflammation
  • cardiovascular disease (CVD)
  • kidney function
  • hormone replacement therapy (HRT)

Published Papers (2 papers)

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Research

20 pages, 1098 KiB  
Article
C11-hydroxy and C11-oxo C19 and C21 Steroids: Pre-Receptor Regulation and Interaction with Androgen and Progesterone Steroid Receptors
by Rachelle Gent, Desmaré Van Rooyen, Stephen L. Atkin and Amanda C. Swart
Int. J. Mol. Sci. 2024, 25(1), 101; https://doi.org/10.3390/ijms25010101 - 20 Dec 2023
Cited by 1 | Viewed by 807
Abstract
C11-oxy C19 and C11-oxy C21 steroids have been identified as novel steroids but their function remains unclear. This study aimed to investigate the pre-receptor regulation of C11-oxy steroids by 11β-hydroxysteroid dehydrogenase (11βHSD) interconversion and potential agonist and antagonist activity associated with [...] Read more.
C11-oxy C19 and C11-oxy C21 steroids have been identified as novel steroids but their function remains unclear. This study aimed to investigate the pre-receptor regulation of C11-oxy steroids by 11β-hydroxysteroid dehydrogenase (11βHSD) interconversion and potential agonist and antagonist activity associated with the androgen (AR) and progesterone receptors (PRA and PRB). Steroid conversions were investigated in transiently transfected HEK293 cells expressing 11βHSD1 and 11βHSD2, while CV1 cells were utilised for agonist and antagonist assays. The conversion of C11-hydroxy steroids to C11-oxo steroids by 11βHSD2 occurred more readily than the reverse reaction catalysed by 11βHSD1, while the interconversion of C11-oxy C19 steroids was more efficient than C11-oxy C21 steroids. Furthermore, 11-ketodihydrotestosterone (11KDHT), 11-ketotestosterone (11KT) and 11β-hydroxydihydrotestosterone (11OHDHT) were AR agonists, while only progestogens, 11β-hydroxyprogesterone (11βOHP4), 11β-hydroxydihydroprogesterone (11βOHDHP4), 11α-hydroxyprogesterone (11αOHP4), 11α-hydroxydihydroprogesterone (11αOHDHP4), 11-ketoprogesterone (11KP4), 5α-pregnan-17α-diol-3,11,20-trione (11KPdione) and 21-deoxycortisone (21dE) exhibited antagonist activity. C11-hydroxy C21 steroids, 11βOHP4, 11βOHDHP4 and 11αOHP4 exhibited PRA and PRB agonistic activity, while only C11-oxo steroids, 11KP4 and 11-ketoandrostanediol (11K3αdiol) demonstrated PRB agonism. While no steroids antagonised the PRA, 11OHA4, 11β-hydroxytestosterone (11OHT), 11KT and 11KDHT exhibited PRB antagonism. The regulatory role of 11βHSD isozymes impacting receptor activation is clear—C11-oxo androgens exhibit AR agonist activity; only C11-hydroxy progestogens exhibit PRA and PRB agonist activity. Regulation by the downstream metabolites of active C11-oxy steroids at the receptor level is apparent—C11-hydroxy and C11-oxo metabolites antagonize the AR and PRB, progestogens the former, androgens the latter. The findings highlight the intricate interplay between receptors and active as well as “inactive” C11-oxy steroids, suggesting novel regulatory tiers. Full article
(This article belongs to the Special Issue Molecular Insights in Steroid Biosynthesis and Metabolism)
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17 pages, 2883 KiB  
Article
Asymmetries of Left and Right Adrenal Glands in Neural Innervation and Glucocorticoids Production
by Rengui Saxu, Yong Yang and Harvest F. Gu
Int. J. Mol. Sci. 2023, 24(24), 17456; https://doi.org/10.3390/ijms242417456 - 14 Dec 2023
Viewed by 920
Abstract
The adrenal gland is paired peripheral end organs of the neuroendocrine system and is responsible for producing crucial stress hormones from its two functional compartments, the adrenal cortex, and the adrenal medulla under stimuli. Left–right asymmetry in vertebrates exists from the central nervous [...] Read more.
The adrenal gland is paired peripheral end organs of the neuroendocrine system and is responsible for producing crucial stress hormones from its two functional compartments, the adrenal cortex, and the adrenal medulla under stimuli. Left–right asymmetry in vertebrates exists from the central nervous system to peripheral paired endocrine glands. The sided difference in the cerebral cortex is extensively investigated, while the knowledge of asymmetry of paired endocrine glands is still poor. The present study aims to investigate the asymmetries of bilateral adrenal glands, which play important roles in stress adaptation and energy homeostasis via steroid hormones produced from the distinct functional zones. Left and right adrenal glands from male C57BL/6J mice were initially histologically analyzed, and high-throughput RNA sequencing was then used to detect the gene transcriptional difference between left and right adrenal glands. Subsequently, the enrichment of functional pathways and ceRNA regulatory work was validated. The results demonstrated that the left adrenal gland had higher tissue mass and levels of energy expenditure, whereas the right adrenal gland appeared to be more potent in glucocorticoid secretion. Further analysis of adrenal stem/progenitor cell markers predicted that Shh signaling might play an important role in the left–right asymmetry of adrenal glands. Of the hub miRNAs, miRNA-466i-5p was identified in the left–right differential innervation of the adrenal glands. Therefore, the present study provides evidence that there are asymmetries between the left and right adrenal glands in glucocorticoid production and neural innervation, in which Shh signaling and miRNA-466i-5p play an important role. Full article
(This article belongs to the Special Issue Molecular Insights in Steroid Biosynthesis and Metabolism)
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