Testicular Maturation Arrest to Testis Cancer: Spectrum of Expression of the Vitamin D Receptor and Vitamin D Treatment In Vitro

Nangia, Ajay K.; Hill, Oya; Waterman, Maudine D.; Schwender, Catherine E.; Memoli, V.

doi:10.1016/j.juro.2007.05.009

Cited by 30 publications

(20 citation statements)

References 13 publications

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“…The expression of VDR and vitamin D metabolising enzymes in human testis, ejaculatory tract and mature spermatozoa (12) suggests a potential role for vitamin D in spermatogenesis and spermatozoa maturation. Specifically, the observed cytoplasmic co-expression of the VDR and vitamin D metabolising enzymes (CYP2R1, CYP27A1 and CYP27B1) in Leydig cells suggests that vitamin D may be linked to male reproductive hormone functioning, although uncertainty remains as to the consistency of some of the immunohistochemistry data (12,31). The observation that VDR knockout mice develop hypergonadotrophic hypogonadism (32) also advocates a potential link between the vitamin D and HPT axes.…”

Section: Discussionmentioning

confidence: 99%

Association of hypogonadism with vitamin D status: the European Male Ageing Study

Lee

Tajar

Pye

et al. 2012

European Journal of Endocrinology

172

144

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Objective: Interrelationships between hormones of the hypothalamic-pituitary-testicular (HPT) axis, hypogonadism, vitamin D and seasonality remain poorly defined. We investigated whether HPT axis hormones and hypogonadism are associated with serum levels of 25-hydroxyvitamin D (25(OH)D) in men. Design and methods: Cross-sectional survey of 3369 community-dwelling men aged 40-79 years in eight European centres. Testosterone (T), oestradiol (E 2 ) and dihydrotestosterone were measured by gas chromatography-mass spectrometry; LH, FSH, sex hormone binding globulin (SHBG), 25(OH)D and parathyroid hormone by immunoassay. Free T was calculated from total T, SHBG and albumin. Gonadal status was categorised as eugonadal (normal T/LH), secondary (low T, low/normal LH), primary (low T, elevated LH) and compensated (normal T, elevated LH) hypogonadism. Associations of HPT axis hormones with 25(OH)D were examined using linear regression and hypogonadism with vitamin D using multinomial logistic regression. Results: In univariate analyses, free T levels were lower (PZ0.02) and E 2 and LH levels were higher (P!0.05) in men with vitamin D deficiency (25(OH)D !50 nmol/l). 25(OH)D was positively associated with total and free T and negatively with E 2 and LH in age-and centre-adjusted linear regressions. After adjusting for health and lifestyle factors, no significant associations were observed between 25(OH)D and individual hormones of the HPT axis. However, vitamin D deficiency was significantly associated with compensated (relative risk ratio (RRR)Z1.52, PZ0.03) and secondary hypogonadism (RRRZ1.16, PZ0.05). Seasonal variation was only observed for 25(OH)D (P!0.001). Conclusions: Secondary and compensated hypogonadism were associated with vitamin D deficiency and the clinical significance of this relationship warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

Association of hypogonadism with vitamin D status: the European Male Ageing Study

Lee

Tajar

Pye

et al. 2012

European Journal of Endocrinology

172

144

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“…These observations suggest that curcuminoid-binding to cells activates signal transduction pathways that lead to dose- or time-dependent reductions in cell division, induction of senescence, or apoptosis. Indeed, curcumin has been identified as an activating ligand for the vitamin D receptor (VDR) [86], which is also highly expressed in NT2/D1 cells [87]. The intracellular VDR could potentially be accessed by curcuminoids via the same cell membrane receptor- or caveolae-mediated mechanisms that are also used to transport steroid hormones [88].…”

Section: Discussionmentioning

confidence: 99%

Curcuminoid Binding to Embryonal Carcinoma Cells: Reductive Metabolism, Induction of Apoptosis, Senescence, and Inhibition of Cell Proliferation

Quitschke

2012

PLoS ONE

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Curcumin preparations typically contain a mixture of polyphenols, collectively referred to as curcuminoids. In addition to the primary component curcumin, they also contain smaller amounts of the co-extracted derivatives demethoxycurcumin and bisdemethoxycurcumin. Curcuminoids can be differentially solubilized in serum, which allows for the systematic analysis of concentration-dependent cellular binding, biological effects, and metabolism. Technical grade curcumin was solubilized in fetal calf serum by two alternative methods yielding saturated preparations containing either predominantly curcumin (60%) or bisdemethoxycurcumin (55%). Continual exposure of NT2/D1 cells for 4–6 days to either preparation in cell culture media reduced cell division (1–5 µM), induced senescence (6–7 µM) or comprehensive cell death (8–10 µM) in a concentration-dependent manner. Some of these effects could also be elicited in cells transiently exposed to higher concentrations of curcuminoids (47 µM) for 0.5–4 h. Curcuminoids induced apoptosis by generalized activation of caspases but without nucleosomal fragmentation. The equilibrium binding of serum-solubilized curcuminoids to NT2/D1 cells incubated with increasing amounts of curcuminoid-saturated serum occurred with apparent overall dissociation constants in the 6–10 µM range. However, the presence of excess free serum decreased cellular binding in a hyperbolic manner. Cellular binding was overwhelmingly associated with membrane fractions and bound curcuminoids were metabolized in NT2/D1 cells via a previously unidentified reduction pathway. Both the binding affinities for curcuminoids and their reductive metabolic pathways varied in other cell lines. These results suggest that curcuminoids interact with cellular binding sites, thereby activating signal transduction pathways that initiate a variety of biological responses. The dose-dependent effects of these responses further imply that distinct cellular pathways are sequentially activated and that this activation is dependent on the affinity of curcuminoids for the respective binding sites. Defined serum-solubilized curcuminoids used in cell culture media are thus suitable for further investigating the differential activation of signal transduction pathways.

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“…It has been shown that testosterone downregulates the VDR in testis cells (42). In cultured human osteoblasts, androgens increase 1a-hydroxylase, a key enzyme in vitamin D metabolism which converts 25(OH)D to the biologically more active form 1,25(OH) 2 D (43).…”

Section: Malesmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Vitamin D and fertility: a systematic review

Lerchbaum

Obermayer-Pietsch

2012

European Journal of Endocrinology

336

252

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Background: Vitamin D has been well-known for its function in maintaining calcium and phosphorus homeostasis and promoting bone mineralization. There is some evidence that in addition to sex steroid hormones, the classic regulators of human reproduction, vitamin D also modulates reproductive processes in women and men. Aim: The aim of this review was to assess the studies that evaluated the relationship between vitamin D and fertility in women and men as well as in animals. Methods: We performed a systematic literature search in Pubmed for relevant English language publications published until October 2011. Results and discussion: The vitamin D receptor (VDR) and vitamin D metabolizing enzymes are found in reproductive tissues of women and men. Vdr knockout mice have significant gonadal insufficiency, decreased sperm count and motility, and histological abnormalities of testis, ovary and uterus. Moreover, we present evidence that vitamin D is involved in female reproduction including IVF outcome (clinical pregnancy rates) and polycystic ovary syndrome (PCOS). In PCOS women, low 25-hydroxyvitamin D (25(OH)D) levels are associated with obesity, metabolic, and endocrine disturbances and vitamin D supplementation might improve menstrual frequency and metabolic disturbances in those women. Moreover, vitamin D might influence steroidogenesis of sex hormones (estradiol and progesterone) in healthy women and high 25(OH)D levels might be associated with endometriosis. In men, vitamin D is positively associated with semen quality and androgen status. Moreover, vitamin D treatment might increase testosterone levels. Testiculopathic men show low CYP21R expression, low 25(OH)D levels, and osteoporosis despite normal testosterone levels.

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Testicular Maturation Arrest to Testis Cancer: Spectrum of Expression of the Vitamin D Receptor and Vitamin D Treatment In Vitro

Cited by 30 publications

References 13 publications

Association of hypogonadism with vitamin D status: the European Male Ageing Study

Association of hypogonadism with vitamin D status: the European Male Ageing Study

Curcuminoid Binding to Embryonal Carcinoma Cells: Reductive Metabolism, Induction of Apoptosis, Senescence, and Inhibition of Cell Proliferation

MECHANISMS IN ENDOCRINOLOGY: Vitamin D and fertility: a systematic review

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