Testosterone increases urinary calcium excretion and inhibits expression of renal calcium transport proteins

Hsu, Yu‐Juei; Dimke, Henrik; Schoeber, Joost P. H.; Hsu, Shih‐Che; Lin, Shih‐Hua; Chu, Pauling; Hoenderop, Joost G. J.; Bindels, René J. M.

doi:10.1038/ki.2009.522

Cited by 69 publications

(55 citation statements)

References 25 publications

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“…1A). These molecular weights are in agreement with those previously reported in the literature (de Talamoni et al 1993, Hsu et al 2010, Kennedy et al 2010. When compared with nonaffected animals, roosters with epididymal lithiasis presented altered expression of the calcium transporting proteins.…”

Section: Resultssupporting

confidence: 83%

“…Roosters affected by epididymal lithiasis had increased levels of TRPV6 and CaBP-D28K but not PMCA and NCX1. It is known that modulation of expression of these proteins is under control of different hormones, such as vitamin D3, estrogens, and androgens (Cai et al 1993, Van Abel et al 2002, Kip & Strehler 2004, Hoenderop et al 2005, Oz et al 2007, Hsu et al 2010. On this sense, we showed recently that roosters with lithiasis presented altered levels of vitamin D3, E 2 , and testosterone that paralleled changes in their receptors (VDR, ESR2, and AR respectively) within the epididymal region (Oliveira et al 2011b).…”

Section: Discussionmentioning

confidence: 80%

“…The transepithelial calcium reabsorption depends on proteins that mediate the apical calcium entry within the cell, named TRPV5 and TRPV6 (transient receptor potential vanilloid channel), the diffusion of the ion throughout the cytoplasm bound to calcium-binding proteins (CaBP), such as CaBP-D9K or CaBP-D28K, and its extrusion to the extracellular environment in the basolateral membranes of the cells by the Na C /Ca 2C exchanger (NCX) or the plasma membrane calmodulin-dependent calcium ATPase (PMCA; Bindels et al 1991, Van Baal et al 1996, Hoenderop et al 2002, 2005, Bar 2009). This process is orchestrated by several hormones that regulate the expression and activity of the aforementioned proteins, including vitamin D3, androgens, and estrogens (Cai et al 1993, Hoenderop et al 2001, 2005, Van Abel et al 2002, Dick et al 2003, Meyer et al 2007, Oz et al 2007, Suzuki et al 2008, Hsu et al 2010, Yang et al 2011. Interestingly, the efferent ductules of roosters express high levels of vitamin D3 receptor (VDR), androgen receptor (AR), and estrogen receptors (ESR1 and ESR2 -also known as ERa and ERb respectively; Kwon et al 1997, Dornas et al 2007, 2008, Oliveira et al 2011a.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of the transepithelial calcium transport disruption and the formation of epididymal stones in roosters

Oliveira¹,

Aquino²,

Mahecha³

et al. 2012

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Epididymal lithiasis is a dysfunction of unknown origin characterized by the formation of calcium stones into the lumen of efferent ductules of roosters. Affected animals present an imbalance in the hormonal responsive systems that regulate the expression of proteins involved in the transepithelial calcium transport, as TRPV6, CaBP-D28K, NCX1, and PMCA. Because the efferent ductules are the major site of fluid and calcium reabsorption in excurrent ducts, it was hypothesized that impairment in local calcium homeostasis would lead to lithiasis. To test this hypothesis, we addressed the expression of these proteins in the epididymal region of affected animals. The present study focused on the investigation of the occurrence, tissue distribution, and physiological impact of the transepithelial calcium transport in roosters under normal and pathological conditions. The results showed that affected roosters presented a significant increase in TRPV6 and CaBP-D28k levels, whereas NCX1 and PMCA were not changed. Such alterations were more conspicuous in the proximal efferent ductules, in which was also observed accumulation of calcium within the epithelial cells. These findings provided the first evidences for the involvement of alteration in the expression of proteins essential for calcium reabsorption as a plausible mechanism for the formation of calcium stones within efferent ductules.

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Section: Resultssupporting

confidence: 83%

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Involvement of the transepithelial calcium transport disruption and the formation of epididymal stones in roosters

Oliveira¹,

Aquino²,

Mahecha³

et al. 2012

Reproduction

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“…Furthermore, estrogen deficiency is known to result in a negative Ca 2ϩ balance and bone loss in postmenopausal women (18). These results partly explain gender differences in renal Ca 2ϩ handling (19). The tissue kallikrein (TK) hormone is secreted into the prourine by renal tubular epithelial cells.…”

Section: Classic Calciotropic Hormones In Controlmentioning

confidence: 88%

Role of the Calcium-Sensing Receptor in Reducing the Risk for Calcium Stones

Renkema

Bindels²,

Hoenderop³

2011

Clinical Journal of the American Society of Nephrology

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SummaryThe tight control of blood Ca 2؉ levels within a narrow range is essential for the performance of vital physiologic functions. Muscle contraction, neuronal excitation, and intracellular signaling processes acquisitively require Ca 2؉ . It is the concerted action of intestine, bone, and kidney that controls the Ca 2؉ balance through the regulation of intestinal absorption, bone (de)mineralization, and renal excretion of Ca 2؉ , respectively. Along the nephron, fine-tuning of blood Ca 2؉ levels takes place by Ca 2؉ reabsorption. The calciotropic hormones regulate Ca 2؉ transport processes, leading to whole-body Ca 2؉ homeostasis and, importantly, preserving a constant Ca 2؉ concentration in the blood. Defects in renal Ca 2؉ handling can lead to hypercalciuria, consecutive kidney stone formation, and obstructive nephropathy. Here we give an overview of the key players involved in normal Ca 2؉ management and describe the in-depth investigations on a renal hypercalciuric model of disease, the Trpv5 knockout mouse, which naturally displays molecular adaptations that prevent Ca 2؉ precipitation in the kidney.

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“…A possible explanation for the observed sex differences could be the role of sex hormones. In animal studies, estrogen was found to stimulate calcium reabsorption in the kidney (21), whereas testosterone was found to inhibit it (22). Alternatively, CYP24A1 or CYP27B1 activity might differ in men and women (23).…”

Section: Discussionmentioning

confidence: 99%

Association of Urinary Calcium Excretion with Serum Calcium and Vitamin D Levels

Rathod

Bonny

Guessous

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Population-based data on urinary calcium excretion are scarce. The association of serum calcium and circulating levels of vitamin D [25(OH)D 2 or D 3 ] with urinary calcium excretion in men and women from a population-based study was explored.Design, settings, participants, & measurements Multivariable linear regression was used to explore factors associated with square root-transformed 24-hour urinary calcium excretion (milligrams per 24 hours) taken as the dependent variable with a focus on month-specific vitamin D tertiles and serum calcium in the Swiss Survey on Salt Study.Results In total, 624 men and 669 women were studied with mean ages of 49.2 and 47.0 years, respectively (age range=15-95 years). Mean urinary calcium excretion was higher in men than in women (183.05 versus 144.60 mg/24 h; P,0.001). In adjusted models, the association (95% confidence interval) of square root urinary calcium excretion with protein-corrected serum calcium was 1.78 (95% confidence interval, 1.21 to 2.34) mg/24 h per milligram per deciliter in women and 0.59 (95% confidence interval, 20.11 to 1.29) mg/24 h per milligram per deciliter in men. Men in the third 25(OH)D 3 tertile had higher square root urinary calcium excretion than men in the first tertile (0.99; 95% confidence interval, 0.36 to 1.63 mg/24 h per nanogram per milliliter), and the corresponding association was 0.32 (95% confidence interval, 20.22 to 0.85) mg/24 h per nanogram per milliliter in women. These sex differences were more marked under conditions of high urinary sodium or urea excretions.Conclusions There was a positive association of serum calcium with urinary calcium excretion in women but not men. Vitamin 25(OH)D 3 was associated with urinary calcium excretion in men but not women. These results suggest important sex differences in the hormonal and dietary control of urinary calcium excretion.

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Testosterone increases urinary calcium excretion and inhibits expression of renal calcium transport proteins

Cited by 69 publications

References 25 publications

Involvement of the transepithelial calcium transport disruption and the formation of epididymal stones in roosters

Involvement of the transepithelial calcium transport disruption and the formation of epididymal stones in roosters

Role of the Calcium-Sensing Receptor in Reducing the Risk for Calcium Stones

Association of Urinary Calcium Excretion with Serum Calcium and Vitamin D Levels

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