scholarly journals Vitamin D as a regulator of steroidogenic enzymes

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 155 ◽  
Author(s):  
Johan Lundqvist

During the last decades, the outlook on vitamin D has widened, from being a vitamin solely involved in bone metabolism and calcium homeostasis, to being a multifunctional hormone known to affect a broad range of physiological processes. The aim of this review is to summarize the research on vitamin D as a regulator of steroidogenic enzymes. Steroid hormones exert a wide range of physiological responses, including functions in the immune system, protein and carbohydrate metabolism, water and salt balance, reproductive system and development of sexual characteristics. The balance of sex hormones is also of importance in the context of breast and prostate cancer. Steroid hormones are synthesized in steroidogenic tissues such as the adrenal cortex, breast, ovaries, prostate and testis, either from cholesterol or from steroidogenic precursors secreted from other steroidogenic tissues. The hormonally active form of vitamin D has been reported to act as a regulator of a number of enzymes involved in the regulation of steroid hormon production, and thereby the production of both adrenal steroid hormones and sex hormones. The research reviewed in the article has in large part been performed in cell culture based experiments and laboratory animal experiments, and the physiological role of the vitamin D mediated regulation of steroidogenic enzyme need to be further investigated.

Reproduction ◽  
2017 ◽  
Vol 154 (6) ◽  
pp. 735-744 ◽  
Author(s):  
Mark S Longtine ◽  
Silvija Cvitic ◽  
Bryanne N Colvin ◽  
Baosheng Chen ◽  
Gernot Desoye ◽  
...  

We assessed the response of primary cultures of placental villous mononucleated trophoblasts and multinucleated syncytiotrophoblast to calcitriol, the most biologically active form of vitamin D. Whole-genome microarray data showed that calcitriol modulates the expression of many genes in trophoblasts within 6 hours of exposure and RT-qPCR revealed similar responses in cytotrophoblasts, syncytiotrophoblasts and villous explants. Both cytotrophoblasts and syncytiotrophoblasts expressed genes for the vitamin D receptor, for LRP2 and CUBN that mediate internalization of calcidiol, forCYP27B1that encodes the enzyme that converts calcidiol into active calcitriol, and forCYP24A1that encodes the enzyme that modifies calcitriol and calcidiol to inactive calcitetrol. Notably, we found an inverse effect of calcitriol on expression of CD14 and CD180/RP105, proteins that differentially regulate toll-like receptor 4-mediated immune responses. Supported by gene ontology analysis, we tested the hypothesis that CD14 and CD180 modulate the inflammatory response of syncytiotrophoblast to bacterial lipopolysaccharide (LPS). These cells showed a robust response to a wide range of LPS concentrations, with induction of active NF-κB and increased secretion of IL-6 and IL-8. SiRNA-mediated knockdown ofCD14reduced the secretion of IL-6 and IL-8 in response to LPS. Collectively, our data showed that calcitriol has a rapid and widespread effect on villous trophoblast gene expression in general, and a specific effect on the innate immune response by syncytiotrophoblast.


2016 ◽  
Vol 96 (1) ◽  
pp. 365-408 ◽  
Author(s):  
Sylvia Christakos ◽  
Puneet Dhawan ◽  
Annemieke Verstuyf ◽  
Lieve Verlinden ◽  
Geert Carmeliet

1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease.


2014 ◽  
Vol 83 (1) ◽  
pp. 73-80
Author(s):  
Bartosz A. Frycz ◽  
Paweł P. Jagodziński

The concentration of sex steroid hormones in the prostate gland is controlled by their local synthesis and metabolism. These processes involve steroid metabolizing (steroidogenic) enzymes, which are necessary to produce the active form of androgens and estrogens at specific locations. Changes in gene expression of the steroid metabolizing enzymes may play an important role in prostate carcinogenesis by regulating sex steroid concentration in the prostate gland. The purpose of this review is to gather the most important reports connected with gene expression of the steroidogenic enzymes and to find correlations between gene expression and tumorigenesis in the prostate gland.


2021 ◽  
Vol 28 ◽  
Author(s):  
Yao Chen ◽  
Jue Hou ◽  
Zhangang Xiao ◽  
Yueshui Zhao ◽  
Fukuan Du ◽  
...  

: Vitamin D as a prohormone is converted into the active form in vivo and binds to vitamin D receptors, exercising a wide range of biological functions. Recent studies strongly support that vitamin D supplementation is associated with reduced cancer risk and a good prognosis. Gastrointestinal cancer is the leading cause of cancer-related deaths worldwide. The key role of vitamin D in the development of gastrointestinal cancer has been observed. Moreover, Vitamin D can also affect innate immunity and perform anti-inflammation and anti-infection actions. Given the intimate relationship between cancer and inflammation, we herein summarize epidemiological and preclinical studies of vitamin D and the underlying mechanism of its action in inflammation, gastric and colorectal cancer by our group and other researchers. A beneficial effect of vitamin D in cancer and inflammatory disease has been supported by different studies. More controlled and larger clinical trials are needed before a reliable conclusion and realization of vitamin D supplementation in the adjunct treatment of gastrointestinal inflammation and cancer.


Author(s):  
Syeda Faryal Fatima ◽  
Syed Zawahir Hassan ◽  
Sadaf Karrar Khan ◽  
Atiqa Bhali

Colon cancer is the third most common type of cancer in the USA and accounts yearly for 11% of all cancer deaths (Center for Disease Control and American Cancer Society). Thus, identifying strategies that reduce its incidence is critically important. Calcitriol, the most active form of vitamin D, is a pleotropic hormone with a wide range of biological activities. Due to its ability to regulate calcium and phosphate metabolism, 1,25D3 plays a major role in bone health. In addition, 1,25D3 binds to the vitamin D receptor and thereby regulates the expression of a number of genes which control growth, differentiation and survival of cancer cells. Although a well-recognized physiological role of vitamin D is the regulation of calcium and phosphate metabolism, recent studies suggest a much broader range of biological functions of vitamin D, including potential anti-neoplastic effects. Garland et al. discovered in 1980 that colon cancer mortality rates in the U.S. were highest in places where populations were exposed to the least amount of sunlight, and proposed that vitamin D might be a protective factor against colon cancer. Since then, extensive studies have reported anti-neoplastic actions of vitamin D, particularly in colorectal cancer. 


2019 ◽  
Vol 17 (6) ◽  
pp. 610-617 ◽  
Author(s):  
Giovanna Muscogiuri ◽  
Luigi Barrea ◽  
Barbara Altieri ◽  
Carolina Di Somma ◽  
Harjit pal Bhattoa ◽  
...  

Vitamin D and calcium are considered crucial for the treatment of bone diseases. Both vitamin D and calcium contribute to bone homeostasis but also preserve muscle health by reducing the risk of falls and fractures. Low vitamin D concentrations result in secondary hyperparathyroidism and contribute to bone loss, although the development of secondary hyperparathyroidism varies, even in patients with severe vitamin D deficiency. Findings from observational studies have shown controversial results regarding the association between bone mineral density and vitamin D/calcium status, thus sparking a debate regarding optimum concentrations of 25-hydroxyvitamin D and calcium for the best possible skeletal health. Although most of the intervention studies reported a positive effect of supplementation with calcium and vitamin D on bone in patients with osteoporosis, this therapeutic approach has been a matter of debate regarding potential side effects on the cardiovascular (CV) system. Thus, the aim of this review is to consider the current evidence on the physiological role of vitamin D and calcium on bone and muscle health. Moreover, we provide an overview on observational and interventional studies that investigate the effect of vitamin D and calcium supplementation on bone health, also taking into account the possible CV side-effects. We also provide molecular insights on the effect of calcium plus vitamin D on the CV system.


Catalysts ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 629
Author(s):  
Aniello Costantini ◽  
Valeria Califano

Lipases are ubiquitous enzymes whose physiological role is the hydrolysis of triacylglycerol into fatty acids. They are the most studied and industrially interesting enzymes, thanks to their versatility to promote a plethora of reactions on a wide range of substrates. In fact, depending on the reaction conditions, they can also catalyze synthesis reactions, such as esterification, acidolysis and transesterification. The latter is particularly important for biodiesel production. Biodiesel can be produced from animal fats or vegetable oils and is considered as a biodegradable, non-toxic and renewable energy source. The use of lipases as industrial catalysts is subordinated to their immobilization on insoluble supports, to allow multiple uses and use in continuous processes, but also to stabilize the enzyme, intrinsically prone to denaturation with consequent loss of activity. Among the materials that can be used for lipase immobilization, mesoporous silica nanoparticles represent a good choice due to the combination of thermal and mechanical stability with controlled textural characteristics. Moreover, the presence of abundant surface hydroxyl groups allows for easy chemical surface functionalization. This latter aspect has the main importance since lipases have a high affinity with hydrophobic supports. The objective of this work is to provide an overview of the recent progress of lipase immobilization in mesoporous silica nanoparticles with a focus on biodiesel production.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Rebecca Callaby ◽  
Emma Hurst ◽  
Ian Handel ◽  
Phil Toye ◽  
Barend M. de C. Bronsvoort ◽  
...  

AbstractVitamin D plays a critical role in calcium homeostasis and in the maintenance and development of skeletal health. Vitamin D status has increasingly been linked to non-skeletal health outcomes such as all-cause mortality, infectious diseases and reproductive outcomes in both humans and veterinary species. We have previously demonstrated a relationship between vitamin D status, assessed by the measurement of serum concentrations of the major vitamin D metabolite 25 hydroxyvitamin D (25(OH)D), and a wide range of non-skeletal health outcomes in companion and wild animals. The aims of this study were to define the host and environmental factors associated with vitamin D status in a cohort of 527 calves from Western Kenya which were part of the Infectious Disease of East African Livestock (IDEAL) cohort. A secondary aim was to explore the relationship between serum 25(OH)D concentrations measured in 7-day old calves and subsequent health outcomes over the following 12 months. A genome wide association study demonstrated that both dietary and endogenously produced vitamin D metabolites were under polygenic control in African calves. In addition, we found that neonatal vitamin D status was not predictive of the subsequent development of an infectious disease event or mortality over the 12 month follow up period.


2002 ◽  
pp. 45-59 ◽  
Author(s):  
K W Colston ◽  
C M√∏rk Hansen

It is now well established that, in addition to its central role in the maintenance of extracellular calcium levels and bone mineralization, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the active form of vitamin D, also acts as a modulator of cell growth and differentiation in a number of cell types, including breast cancer cells. The anti-proliferative effects of 1,25(OH)(2)D(3) have been linked to suppression of growth stimulatory signals and potentiation of growth inhibitory signals, which lead to changes in cell cycle regulators such as p21(WAF-1/CIP1) and p27(kip1), cyclins and retinoblastoma protein as well as induction of apoptosis. Such studies have led to interest in the potential use of 1,25(OH)(2)D(3) in the treatment or prevention of certain cancers. Since this approach is limited by the tendency of 1,25(OH)(2)D(3) to cause hypercalcaemia, synthetic vitamin D analogues have been developed which display separation of the growth regulating effects from calcium mobilizing actions. This review examines mechanisms by which 1,25(OH)(2)D(3) and its active analogues exert both anti-proliferative and pro-apoptotic effects and describes some of the synthetic analogues that have been shown to be of particular interest in relation to breast cancer.


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