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Steroid Hormones and Human Health

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (15 January 2019) | Viewed by 49299

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Guest Editor
Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK
Interests: nutrition; stress; exercise; polyphenols; steroid hormones
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Steroid hormones are small lipophilic compounds derived from cholesterol that play a number of vital and important physiological roles. They are usually found in the body, either in a conjugated form as sulfate or glucuronide derivatives, or bound to proteins. Steroid hormones are synthesized mainly by endocrine glands such as the gonads (testis and ovary), the adrenals (glucocorticoids, mineralocrticoids and androgen precursors) and placenta during gestation. The CNS is also able to make a number of biologically active steroids called "neurosteroids", which are responsible for key CNS pathways involved in the long-term control of sympathetic and neuro-endocrine function, cardiovascular homeostasis and several other physiological functions. The biological activity of a steroid molecule depends on its ability to interact with a specific binding site on the corresponding receptor. Steroid hormones help control metabolism, inflammation, immune functions, salt and water balance, development of sexual characteristics, and the ability to withstand illness and injury.

Different classes of steroid hormones regulate and coordinate biochemical, physiological and behavioural responses of various biological activities, e.g., Glucocorticoids with their known effects on carbohydrate, lipid and protein metabolism (obesity, metabolic syndrome, etc.) stress response and the immune system, Sex steroids and their effects on reproduction and human behaviour. Vit D as a steroid hormone was proved to be  essential for good health due to its multipotent physiological and biochemical actions throughout the body. The androgen precursor, Dehydroepiandrosterone is one of the most abundant steroid hormones in the human body that possesses multiple actions which need to be fully investigated. DHEA has been linked to improvement in cognitive function, immune system strengthening and providing an antagonistic action towards the stress hormone, cortisol. Bioactive androgens (11b-OH-testosterone, oxotestosterone and OH-androsterone) are discovered to have potential physiological importance in humans. In fact, Steroids can act as coregulators and coactivators in health and disease. Metabolism plays an important role in steroid hormone action and formation of active metabolites in target tissues is important for the regulation of their cellular and physiological actions (many disorders result from defects in target tissue metabolism). Several enzymes are involved in steroid biosynthesis and thus a number of endocrine disorders can be attributed to specific enzyme defects.

Nutrition can be used to treat several disorders, for example, stress by reducing cortisol levels, while the B vitamins can stimulate fatigued adrenal glands. "A nutritious diet filled with antioxidants from brightly coloured fruits and vegetables can also support immune health which may be well appreciated when stressed”. Several studies have investigated whether the type of macronutrient influences the postprandial response of cortisol. Research and clinical studies have now associated plant-based diet intake with various beneficial health and biological activities. Functional nutrients have become essential not only for energy production and body matter of classic metabolism, but also a conditioning environment that modulates the epigenome activity and influences stress adaptive responses, energy metabolism, immune homeostasis, and disease prevention. We have reported that polyphenols in pomegranate and green coffee can inhibit 11B-HSD1 activity, thereby improving mood and reducing stress by causing a slight reduction in blood pressure and the levels of the stress hormone, cortisol. Therefore, polyphenols-rich diet may exert its health beneficial effects through multiple mode of actions affecting various cellular pathways, and most likely, steroid hormones modulation represents an important factor.

 Topics:

  1. Nutritional regulation of steroid hormones metabolism/action
  2. Physiological importance of bioactive androgens
  3. Sex steroids and behaviour
  4. Role of vitamin D in human health
  5. Steroid hormones, cognitive function and healthy ageing
  6. Steroid hormones in dairy foods and impact on public health
Prof. Emad Al-Dujaili
Guest Editor

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Keywords

  • Steroid hormones
  • Stress
  • Nutrition
  • Exercise
  • Polyphenols

Published Papers (8 papers)

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Research

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9 pages, 987 KiB  
Communication
‘Central’ Actions of Corticosteroid Signaling Suggested by Constitutive Knockout of Corticosteroid Receptors in Small Fish
by Tatsuya Sakamoto and Hirotaka Sakamoto
Nutrients 2019, 11(3), 611; https://doi.org/10.3390/nu11030611 - 13 Mar 2019
Cited by 6 | Viewed by 2993
Abstract
This review highlights recent studies of the functional implications of corticosteroids in some important behaviors of model fish, which are also relevant to human nutrition homeostasis. The primary actions of corticosteroids are mediated by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), which are [...] Read more.
This review highlights recent studies of the functional implications of corticosteroids in some important behaviors of model fish, which are also relevant to human nutrition homeostasis. The primary actions of corticosteroids are mediated by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), which are transcription factors. Zebrafish and medaka models of GR- and MR-knockout are the first constitutive corticosteroid receptor-knockout animals that are viable in adulthood. Similar receptor knockouts in mice are lethal. In this review, we describe the physiological and behavioral changes following disruption of the corticosteroid receptors in these models. The GR null model has peripheral changes in nutrition metabolism that do not occur in a mutant harboring a point mutation in the GR DNA-binding domain. This suggests that these are not “intrinsic” activities of GR. On the other hand, we propose that integration of visual responses and brain behavior by corticosteroid receptors is a possible “intrinsic”/principal function potentially conserved in vertebrates. Full article
(This article belongs to the Special Issue Steroid Hormones and Human Health)
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11 pages, 1151 KiB  
Article
Post-Prandial Changes in Salivary Glucocorticoids: Effects of Dietary Cholesterol and Associations with Bile Acid Excretion
by Graham W. Anderson, Christopher J. Kenyon and Emad A.S. Al-Dujaili
Nutrients 2019, 11(2), 360; https://doi.org/10.3390/nu11020360 - 09 Feb 2019
Cited by 3 | Viewed by 3113
Abstract
Mechanisms to explain post-prandial increases in circulating glucocorticoids are not well understood and may involve increased adrenal secretion and/or altered steroid metabolism. We have compared salivary levels of cortisol and cortisone levels in healthy male and female volunteers fed either a low or [...] Read more.
Mechanisms to explain post-prandial increases in circulating glucocorticoids are not well understood and may involve increased adrenal secretion and/or altered steroid metabolism. We have compared salivary levels of cortisol and cortisone levels in healthy male and female volunteers fed either a low or cholesterol-rich midday meal. Urinary levels of steroids, bile acids and markers of lipid peroxidation were also measured. Males and females showed expected circadian changes in salivary steroids and postprandial peaks within 1h of feeding. After a high-cholesterol meal, postprandial cortisol increases were higher in males whereas post-prandial cortisone levels were higher in females. Urinary cortisol but not cortisone levels were higher on the day when males and females ate a high-cholesterol meal. Urinary bile acid excretion and anti-oxidant markers of lipid peroxidation, thiobarbituric acid reactive substances (TBARS), and total phenol content were not affected by dietary cholesterol but tended to be higher in males. Cross-tabulation of correlation coefficients indicated positive associations between urinary markers of peroxidation, bile acids, and cortisol:cortisone ratios. We conclude that dietary cholesterol (a substrate for steroidogenesis) does not have an acute effect on adrenal glucocorticoid synthesis and that gender but not a high-cholesterol meal may influence the interconversion of cortisol and cortisone. Longer term studies of the effects of dietary cholesterol are needed to analyze the associations between bile acids, steroid metabolism, and secretion and lipid peroxidation. Full article
(This article belongs to the Special Issue Steroid Hormones and Human Health)
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13 pages, 569 KiB  
Article
A Short Study Exploring the Effect of the Glycaemic Index of the Diet on Energy intake and Salivary Steroid Hormones
by Emad A.S. Al-Dujaili, Sophie Ashmore and Catherine Tsang
Nutrients 2019, 11(2), 260; https://doi.org/10.3390/nu11020260 - 24 Jan 2019
Cited by 4 | Viewed by 4711
Abstract
Background: The glycaemic index or load (GI or GL) is a concept for ranking carbohydrate-rich foods based on the postprandial blood glucose response compared with a reference food (glucose). Due to the limited research investigating the effect of the GI or GL of [...] Read more.
Background: The glycaemic index or load (GI or GL) is a concept for ranking carbohydrate-rich foods based on the postprandial blood glucose response compared with a reference food (glucose). Due to the limited research investigating the effect of the GI or GL of the diet on salivary steroidal hormones, this explorative short study was conducted. Methods: 12 female participants consumed a low GI and a high GI diet for three days each, followed by a washout period between each intervention. Saliva was collected at baseline, and following the low or high GI diets. Cortisol and testosterone concentrations were measured by enzyme-linked immuno-sorbent assay (ELISA). Results: GI and GL were significantly different between the low and high GI diets (p < 0.001). There was a small but significant increase in salivary cortisol after the high GI diet (7.38 to 10.93 ng/mL, p = 0.036). No effect was observed after the low GI diet. Higher levels of testosterone were produced after the low GI diet (83.7 to 125.9 pg/mL, p = 0.002), and no effect was found after the high GI diet. The total intake of calories consumed on the low GI diet was significantly lower compared to the high GI diet (p = 0.019). Conclusions: A low GI diet was associated with a small but significant increase in salivary testosterone, while a high GI diet increased cortisol levels. Altering the GI of the diet may influence overall energy intake and the health and wellbeing of female volunteers. Full article
(This article belongs to the Special Issue Steroid Hormones and Human Health)
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9 pages, 888 KiB  
Article
The Association between Breastmilk Glucocorticoid Concentrations and Macronutrient Contents Throughout the Day
by Jonneke J. Hollanders, Stefanie M. P. Kouwenhoven, Bibian van der Voorn, Johannes B. van Goudoever, Joost Rotteveel and Martijn J. J. Finken
Nutrients 2019, 11(2), 259; https://doi.org/10.3390/nu11020259 - 24 Jan 2019
Cited by 13 | Viewed by 3486
Abstract
Background: Glucocorticoids (GCs) in breastmilk follow the maternal hypothalamus–pituitary–adrenal axis activity and may affect the offspring’s growth and neurodevelopment. There is some evidence suggesting that macronutrients in breastmilk also fluctuate throughout the day. We aimed to research whether GCs and macronutrients are correlated [...] Read more.
Background: Glucocorticoids (GCs) in breastmilk follow the maternal hypothalamus–pituitary–adrenal axis activity and may affect the offspring’s growth and neurodevelopment. There is some evidence suggesting that macronutrients in breastmilk also fluctuate throughout the day. We aimed to research whether GCs and macronutrients are correlated in multiple breastmilk samples obtained over a 24-h period. Methods: A total of 10 mothers provided 45 breastmilk samples collected over a 24-h period. Cortisol and cortisone levels were determined by LC–MS/MS, and macronutrients were measured with mid-infrared spectroscopy. Correlations between breastmilk GCs and macronutrients were assessed with Pearson correlations and linear mixed models. Results: No associations were found between breastmilk GCs and macronutrients (cortisol: β-0.1 (95% confidence interval: −1.0 to 0.7), −4.9 (−12.9 to 3.1) for fat, protein, and carbohydrates, respectively; and −0.3 (−5.6 to 5.0) and cortisone: 0.0 (−2.5 to 2.5), −17.4 (−39.8 to 5.0), and −2.7 (−17.7 to 12.3)) for fat, protein, and carbohydrates, respectively. Adjusting for the time of collection to account for GC rhythmicity did not change the results. Conclusion: We found no associations between GCs and macronutrients in human breastmilk. The excretion of GCs in breastmilk and the effects of breastmilk GCs on offspring are, therefore, likely independent of the excretion and effects of the macronutrients. Full article
(This article belongs to the Special Issue Steroid Hormones and Human Health)
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12 pages, 554 KiB  
Article
A Randomized, Controlled Trial of Vitamin D Supplementation on Cardiovascular Risk Factors, Hormones, and Liver Markers in Women with Polycystic Ovary Syndrome
by Zeeshan Javed, Maria Papageorgiou, Harshal Deshmukh, Eric S. Kilpatrick, Vincent Mann, Lynsey Corless, George Abouda, Alan S. Rigby, Stephen L. Atkin and Thozhukat Sathyapalan
Nutrients 2019, 11(1), 188; https://doi.org/10.3390/nu11010188 - 17 Jan 2019
Cited by 56 | Viewed by 12651
Abstract
Polycystic ovary syndrome (PCOS) increases the risk of metabolic syndrome and non-alcoholic-fatty-liver disease (NAFLD). Vitamin D supplementation may exert positive effects on liver biochemistry in patients with NAFLD; however, its effects on PCOS are unknown. This randomized, double-blind, placebo-controlled study explored the effect [...] Read more.
Polycystic ovary syndrome (PCOS) increases the risk of metabolic syndrome and non-alcoholic-fatty-liver disease (NAFLD). Vitamin D supplementation may exert positive effects on liver biochemistry in patients with NAFLD; however, its effects on PCOS are unknown. This randomized, double-blind, placebo-controlled study explored the effect of vitamin D supplementation on cardiovascular risk factors (high-sensitivity C-reactive protein (hs-CRP), weight, body mass index (BMI), lipid profile, glucose levels, insulin levels, the homeostatic model assessment-insulin resistance (HOMA-IR), hormones (free androgen index (FAI), testosterone, sex hormone binding globulin (SHBG), and liver markers (alanine aminotransferase (ALT), hyaluronic acid (HA), N-terminal pro-peptide of type III procollagen (PIIINP), tissue inhibitor of metallo-proteinases-1 (TIMP-1), and the enhanced liver fibrosis (ELF) score). Forty women with PCOS were recruited and randomized to vitamin D (3200 IU) or placebo daily for 3 months. All outcomes were measured at baseline and 3 months follow-up (FU). Greater increases in vitamin D levels were shown in the supplementation group (vitamin D, baseline: 25.6 ± 11.4 nmol/L, FU: 90.4 ± 19.5 nmol/L vs. placebo, baseline: 30.9 ± 11.1 nmol/L, FU: 47.6 ± 20.5 nmol/L, p < 0.001). Between groups comparisons (% baseline change) revealed significant differences in ALT (p = 0.042) and a weak effect indicating a greater reduction in the HOMA-IR in the vitamin D group (p = 0.051). No further between group differences were seen in other cardiovascular risk factor, liver markers, or hormones. This study supports beneficial effects of vitamin D supplementation on liver markers and modest improvements in insulin sensitivity in vitamin D deficient women with PCOS. Full article
(This article belongs to the Special Issue Steroid Hormones and Human Health)
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12 pages, 1924 KiB  
Article
Adipocytes ESR1 Expression, Body Fat and Response to Testosterone Therapy in Hypogonadal Men Vary According to Estradiol Levels
by Georgia Colleluori, Lina E. Aguirre, Clifford Qualls, Rui Chen, Nicola Napoli, Dennis T. Villareal and Reina Armamento-Villareal
Nutrients 2018, 10(9), 1226; https://doi.org/10.3390/nu10091226 - 04 Sep 2018
Cited by 9 | Viewed by 5404
Abstract
Estradiol (E2), mainly produced from Testosterone (T) in men, promotes visceral lipolysis. However, high visceral fat and hyperestrogenemia are features of obese hypogonadal (HG) men. Our study objectives are to evaluate relationships between circulating E2 and: (1) fat mass; (2) Estrogen Receptor α [...] Read more.
Estradiol (E2), mainly produced from Testosterone (T) in men, promotes visceral lipolysis. However, high visceral fat and hyperestrogenemia are features of obese hypogonadal (HG) men. Our study objectives are to evaluate relationships between circulating E2 and: (1) fat mass; (2) Estrogen Receptor α (ESR1) expression in subcutaneous adipose tissue; (3) changes in body fat after 6 months (M) of T therapy in HG men. Hypotheses: (1) existence of a range of circulating E2 associated with better body composition; (2) serum E2 determines tissue E2 sensitivity which affects response to T therapy. Men 40–74 years old, T < 300 (ng/dL), given T-cypionate for 6 months. Subjects were divided into 4-E2 categories: (1) <10.0; (2) 10.0–15.9; (3) 16.0–19.9; (4) ≥20.0 (pg/mL). Body composition (DXA), fat biopsies (liposuction), gene expression (qPCR), serum E2 and T (LC/MS), at baseline and 6 months. We enrolled 105 men; 90 completed the study. Group 2 had lower total and truncal fat mass (p < 0.01) but higher % lean mass (p < 0.001). ESR1 mRNA was the highest in group 1 (p = 0.01). At 6 months, group 1 had higher reduction in total (p = 0.03) and truncal (p = 0.01) fat. In conclusion, serum E2 = 10–15.9 (pg/mL) is associated with the best body composition profile in HG men; however, those with E2 < 10 (pg/mL) had the best response (greater fat loss) to T replacement possibly because of greater E2 sensitivity. Full article
(This article belongs to the Special Issue Steroid Hormones and Human Health)
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Review

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11 pages, 234 KiB  
Review
Antitumor Effect of Various Phytochemicals on Diverse Types of Thyroid Cancers
by Hye-Ji Shin, Kyung-A Hwang and Kyung-Chul Choi
Nutrients 2019, 11(1), 125; https://doi.org/10.3390/nu11010125 - 09 Jan 2019
Cited by 31 | Viewed by 5289
Abstract
Thyroid cancers developed from the tissues of the thyroid gland are classified into papillary (PTC), follicular (FTC), medullary (MTC), and anaplastic thyroid cancer (ATC). Although thyroid cancers have been generally known as mild forms of cancer, undifferentiated MTC and ATC have a more [...] Read more.
Thyroid cancers developed from the tissues of the thyroid gland are classified into papillary (PTC), follicular (FTC), medullary (MTC), and anaplastic thyroid cancer (ATC). Although thyroid cancers have been generally known as mild forms of cancer, undifferentiated MTC and ATC have a more unfavorable prognosis than differentiated PTC and FTC because they are more aggressive and early metastatic. A variety of therapies such as surgery, radiotherapy, and chemotherapy have been currently used to treat thyroid cancer, but they still have limitations including drug resistance or unfavorable side effects. Phytochemicals are plant-derived chemicals having various physiological activities that are expected to be effective in cancer treatment. In this review, anticancer efficacy of phytochemicals, such as resveratrol, genistein, curcumin, and other substances in each type of thyroid cancer was introduced with their chemopreventive mechanisms. English articles related with thyroid cancer and anti-thyroid cancer of phytochemicals were searched from PubMed and Google Scholar. This article mainly focused on in vitro or animal studies on phytochemicals with anti-thyroid cancer activity. These various phytochemicals have been shown to induce apoptosis in all types of thyroid cancer cells, inhibit cell proliferation and invasion, and to be helpful in enhancing the effect of radioiodine therapy that is a typical therapy to thyroid cancer. These results suggest that thyroid cancer can be more effectively treated by the combinations of phytochemicals and the existing therapies or substances. Full article
(This article belongs to the Special Issue Steroid Hormones and Human Health)
10 pages, 287 KiB  
Review
Flash Glucose Monitoring: A Review of the Literature with a Special Focus on Type 1 Diabetes
by Giulia Mancini, Maria Giulia Berioli, Elisa Santi, Francesco Rogari, Giada Toni, Giorgia Tascini, Roberta Crispoldi, Giulia Ceccarini and Susanna Esposito
Nutrients 2018, 10(8), 992; https://doi.org/10.3390/nu10080992 - 29 Jul 2018
Cited by 49 | Viewed by 7517
Abstract
In people with type 1 diabetes mellitus (T1DM), obtaining good glycemic control is essential to reduce the risk of acute and chronic complications. Frequent glucose monitoring allows the adjustment of insulin therapy to improve metabolic control with near-normal blood glucose concentrations. The recent [...] Read more.
In people with type 1 diabetes mellitus (T1DM), obtaining good glycemic control is essential to reduce the risk of acute and chronic complications. Frequent glucose monitoring allows the adjustment of insulin therapy to improve metabolic control with near-normal blood glucose concentrations. The recent development of innovative technological devices for the management of T1DM provides new opportunities for patients and health care professionals to improve glycemic control and quality of life. Currently, in addition to traditional self-monitoring of blood glucose (SMBG) through a glucometer, there are new strategies to measure glucose levels, including the detection of interstitial glucose through Continuous Glucose Monitoring (iCGM) or Flash Glucose Monitoring (FGM). In this review, we analyze current evidence on the efficacy and safety of FGM, with a special focus on T1DM. FGM is an effective tool with great potential for the management of T1DM both in the pediatric and adult population that can help patients to improve metabolic control and quality of life. Although FGM might not be included in the development of an artificial pancreas and some models of iCGM are more accurate than FGM and preferable in some specific situations, FGM represents a cheaper and valid alternative for selected patients. In fact, FGM provides significantly more data than the intermittent results obtained by SMBG, which may not capture intervals of extreme variability or nocturnal events. With the help of a log related to insulin doses, meal intake, physical activity and stress factors, people can achieve the full benefits of FGM and work together with health care professionals to act upon the information provided by the sensor. The graphs and trends available with FGM better allow an understanding of how different factors (e.g., physical activity, diet) impact glycemic control, consequently motivating patients to take charge of their health. Full article
(This article belongs to the Special Issue Steroid Hormones and Human Health)
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