Calcium transport in male reproduction is possibly influenced by vitamin D and CaSR

2021 ◽  
Author(s):  
Ida Marie Boisen ◽  
John Erik Nielsen ◽  
Lieve Verlinden ◽  
Mette Lorenzen ◽  
Rune Holt ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Transport ◽  
Calcium Concentration ◽  
Transient Receptor Potential ◽  
Reproductive Tract ◽  
Receptor Potential ◽  
Male Reproduction ◽  
Human Testis ◽  
Transient Receptor Potential Vanilloid ◽  
Male Reproductive Tract

Vitamin D is important for gonadal function in rodents, and improvement of vitamin D status in men with low sperm counts increases live birth rate. Vitamin D is a regulator of transcellular calcium transport in the intestine and kidney and may influence the dramatic changes in the luminal calcium concentration in epididymis. Here, we show spatial expression in the male reproductive tract of vitamin D receptor (VDR)-regulated factors involved in calcium transport: Transient receptor potential vanilloid 5/6 (TRPV5/6), sodium/calcium exchanger 1 (NCX1), plasma membrane calcium ATPase 1 (PMCA1), calbindin D9k, calcium-sensing receptor (CaSR), and parathyroid hormone-related peptide (PTHrP) in mouse and human testis and epididymis. Testicular Casr expression was lower in Vdr ablated mice compared with controls. Moreover, expression levels of Casr and Pthrp were strongly correlated in both testis and epididymis and Pthrp was suppressed by 1,25(OH)2D3 in a spermatogonial cell line. The expression of CaSR in epididymis may be of greater importance than in the gonad in mice as germ cell-specific Casr deficient mice had no major reproductive phenotype, and coincubation with a CaSR-agonist had no effect on human sperm-oocyte binding. In humans, seminal calcium concentration between 5-10 mM was associated with a higher fraction of motile and morphologically normal sperm cells and the seminal calcium concentration was not associated with serum calcium levels. In conclusion, VDR regulates CaSR and PTHrP, and both factors may be involved in the regulation of calcium transport in the male reproductive tract with possible implications for sperm function and storage.

scholarly journals Evidence for a Role of Prolactin in Calcium Homeostasis: Regulation of Intestinal Transient Receptor Potential Vanilloid Type 6, Intestinal Calcium Absorption, and the 25-Hydroxyvitamin D3 1α Hydroxylase Gene by Prolactin

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 2974-2984 ◽  
Author(s):  
Dare V. Ajibade ◽  
Puneet Dhawan ◽  
Adam J. Fechner ◽  
Mark B. Meyer ◽  
J. Wesley Pike ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Homeostasis ◽  
Calcium Transport ◽  
Transient Receptor Potential ◽  
Prolactin Receptor ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Calbindin D9k ◽  
Intestinal Calcium Transport ◽  
Transient Receptor

Increased calcium transport has been observed in vitamin D-deficient pregnant and lactating rats, indicating that another factor besides 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is involved in intestinal calcium transport. To investigate prolactin as a hormone involved in calcium homeostasis, vitamin D-deficient male mice were injected with 1,25(OH)2D3, prolactin, or prolactin + 1,25(OH)2D3. Prolactin alone (1 μg/g body weight 48, 24, and 4 h before termination) significantly induced duodenal transient receptor potential vanilloid type 6 (TRPV6) mRNA (4-fold) but caused no change in calbindin-D9k. Combined treatment with 1,25(OH)2D3 and prolactin resulted in an enhancement of the 1,25(OH)2D3 induction of duodenal TRPV6 mRNA, calbindin-D9k mRNA, and an induction of duodenal calcium transport [P < 0.05 compared with 1,25(OH)2D3 alone]. Because lactation is associated with an increase in circulating 1,25(OH)2D3, experiments were done to determine whether prolactin also has a direct effect on induction of 25-hydroxyvitamin D3 1α hydroxylase [1α(OH)ase]. Using AOK B-50 cells cotransfected with the prolactin receptor and the mouse 1α(OH)ase promoter −1651/+22 cooperative effects between prolactin and signal transducer and activator of transcription 5 were observed in the regulation of 1α(OH)ase. In addition, in prolactin receptor transfected AOK B-50 cells, prolactin treatment (400 ng/ml) and signal transducer and activator of transcription 5 significantly induced 1α(OH)ase protein as determined by Western blot analysis. Thus, prolactin, by multiple mechanisms, including regulation of vitamin D metabolism, induction of TRPV6 mRNA, and cooperation with 1,25(OH)2D3 in induction of intestinal calcium transport genes and intestinal calcium transport, can act as an important modulator of vitamin D-regulated calcium homeostasis.

scholarly journals Active Intestinal Calcium Transport in the Absence of Transient Receptor Potential Vanilloid Type 6 and Calbindin-D9k

Endocrinology ◽  
2008 ◽  
Vol 149 (6) ◽  
pp. 3196-3205 ◽  
Author(s):  
Bryan S. Benn ◽  
Dare Ajibade ◽  
Angela Porta ◽  
Puneet Dhawan ◽  
Matthias Hediger ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Transport ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Fold Increase ◽  
Transient Receptor Potential Vanilloid ◽  
Low Calcium Diet ◽  
Calbindin D9k ◽  
Intestinal Calcium Transport ◽  
Transient Receptor

To study the role of the epithelial calcium channel transient receptor potential vanilloid type 6 (TRPV6) and the calcium-binding protein calbindin-D9k in intestinal calcium absorption, TRPV6 knockout (KO), calbindin-D9k KO, and TRPV6/calbindin-D9k double-KO (DKO) mice were generated. TRPV6 KO, calbindin-D9k KO, and TRPV6/calbindin-D9k DKO mice have serum calcium levels similar to those of wild-type (WT) mice (∼10 mg Ca2+/dl). In the TRPV6 KO and the DKO mice, however, there is a 1.8-fold increase in serum PTH levels (P < 0.05 compared with WT). Active intestinal calcium transport was measured using the everted gut sac method. Under low dietary calcium conditions there was a 4.1-, 2.9-, and 3.9-fold increase in calcium transport in the duodenum of WT, TRPV6 KO, and calbindin-D9k KO mice, respectively (n = 8–22 per group; P > 0.1, WT vs. calbindin-D9k KO, and P < 0.05, WT vs. TRPV6 KO on the low-calcium diet). Duodenal calcium transport was increased 2.1-fold in the TRPV6/calbindin-D9k DKO mice fed the low-calcium diet (P < 0.05, WT vs. DKO). Active calcium transport was not stimulated by low dietary calcium in the ileum of the WT or KO mice. 1,25-Dihydroxyvitamin D3 administration to vitamin D-deficient null mutant and WT mice also resulted in a significant increase in duodenal calcium transport (1.4- to 2.0-fold, P < 0.05 compared with vitamin D-deficient mice). This study provides evidence for the first time using null mutant mice that significant active intestinal calcium transport occurs in the absence of TRPV6 and calbindin-D9k, thus challenging the dogma that TRPV6 and calbindin-D9k are essential for vitamin D-induced active intestinal calcium transport.

scholarly journals Vitamin D is an endogenous partial agonist of the transient receptor potential vanilloid 1 channel

2020 ◽  
Vol 598 (19) ◽  
pp. 4321-4338 ◽  
Author(s):  
Wentong Long ◽  
Mohammad Fatehi ◽  
Shubham Soni ◽  
Rashmi Panigrahi ◽  
Koenraad Philippaert ◽  
...  
Keyword(s):  
Vitamin D ◽  
Transient Receptor Potential ◽  
Partial Agonist ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

scholarly journals Immunoregulation in the testis and its implication in fertility and infections

2021 ◽  
Author(s):  
Kushaan Khambata ◽  
Deepak Modi ◽  
Satish Gupta
Keyword(s):  
Reproductive Tract ◽  
Viral Infections ◽  
The Body ◽  
Male Reproduction ◽  
Human Testis ◽  
Male Reproductive Tract ◽  
Inflammatory Conditions ◽  
Immunodeficiency Virus ◽  
Sperm Antigens ◽  
Sperm Antibodies

The testis is designated as one of the immune previleged sites in the body and harbours a unique immunoregulatory environment, which is important for preventing an immune response against sperm antigens which otherwise are recognized as “foreign” by the immune system. The blood-testis barrier along with the unique immune cells repertoire and various immunoregulatory & immunosuppressive factors secreted by the Leydig cells, Sertoli cells and peritubular cells act in concert to maintain the tolerogenic environment in the testis. Abberations in immunotolerant mechanisms in the testis can lead to generation of anti-sperm antibodies that have an association with male infertility. It can also lead to inflammatory conditions of the male reproductive tract manifested as epididymitis and orchitis, generally due to bacterial or viral infections. In addition, non-infectious epididymitis and orchitis, having autoimmune origin have also been reported in males. While the immune privilege status of human testis protects the germ cells from an immune attack, it can also make the testis a succeptible reservoir for viruses such as human immunodeficiency virus-1, Zika virus and severe acute respiratory syndrome coronavirus-2, all of which have adverse consequences on male reproduction.

scholarly journals Accumulation of intramyocyte TRPV1-mediated calcium during heat stress is inhibited by concomitant muscle contractions

2019 ◽  
Vol 126 (3) ◽  
pp. 691-698 ◽  
Author(s):  
Ryo Ikegami ◽  
Hiroaki Eshima ◽  
Takuro Mashio ◽  
Tomosada Ishiguro ◽  
Daisuke Hoshino ◽  
...  
Keyword(s):  
Heat Stress ◽  
Muscle Contraction ◽  
Isometric Contraction ◽  
Calcium Concentration ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Channels ◽  
Transient Receptor

Heat stress promotes intramyocyte calcium concentration ([Ca2+]i) accumulation via transient receptor potential vanilloid 1 (TRPV1) channels. We tested the hypothesis that muscle contractile activity concomitant with heat stress would accelerate the increase in [Ca2+]i via TRPV1, further impairing [Ca2+]i homeostasis. Spinotrapezius muscles of adult Wistar rats were exteriorized in vivo and loaded with the fluorescent Ca2+ probe fura 2-AM. Heat stress (muscle surface temperature 40°C) was used as TRPV1 activator. An isometric contraction (100 Hz, 5–10 V, 30 s) was induced electrically concomitant with heat stress. [Ca2+]i was determined for 20 min using in vivo fluorescence microscopy, and the phosphorylation response of TRPV1 was determined by Western blotting. Heat stress induced a significant [Ca2+]i increase of 18.5 ± 8.1% at 20 min and TRPV1 phosphorylation (+231%), which was inhibited by addition of the TRPV1 inhibitor (capsazepine). However, contrary to expectations, the heat stress and isometric contraction condition almost completely inhibited TRPV1 phosphorylation and the consequent [Ca2+]i elevation (<2.8% accumulation during heat stress, P > 0.05). In conclusion, this in vivo physiological model demonstrated that isometric muscle contraction(s) can suppress the phosphorylation response of TRPV1 and maintain [Ca2+]i homeostasis during heat stress. NEW & NOTEWORTHY This investigation is the first document the dynamics of intramyocyte calcium concentration ([Ca2+]i) increase in the myoplasm of skeletal muscle fibers in response to heat stress where the muscle blood flow is preserved. Heat stress at 40°C drives a myoplasmic [Ca2+]i accumulation in concert with transient receptor potential vanilloid 1 (TRPV1) phosphorylation. However, muscle contraction caused TRPV1 channel deactivation by dephosphorylation of TRPV1. TRPV1 inactivation via isometric contraction(s) permits maintenance of [Ca2+]i homeostasis even under high imposed muscle temperature.

Segmental transport of Ca2+ and Mg2+ along the gastrointestinal tract

2015 ◽  
Vol 308 (3) ◽  
pp. G206-G216 ◽  
Author(s):  
Anke L. Lameris ◽  
Pasi I. Nevalainen ◽  
Daphne Reijnen ◽  
Ellen Simons ◽  
Jelle Eygensteyn ◽  
...  
Keyword(s):  
Vitamin D ◽  
Gastrointestinal Tract ◽  
Intestinal Absorption ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
The Body ◽  
Time Dependent ◽  
Transient Receptor Potential Vanilloid ◽  
Dependent Manner ◽  
Transient Receptor

Calcium (Ca2+) and magnesium (Mg2+) ions are involved in many vital physiological functions. Since dietary intake is the only source of minerals for the body, intestinal absorption is essential for normal homeostatic levels. The aim of this study was to characterize the absorption of Ca2+ as well as Mg2+ along the gastrointestinal tract at a molecular and functional level. In both humans and mice the Ca2+ channel transient receptor potential vanilloid subtype 6 (TRPV6) is expressed in the proximal intestinal segments, whereas Mg2+ channel transient receptor potential melastatin subtype 6 (TRPM6) is expressed in the distal parts of the intestine. A method was established to measure the rate of Mg2+ absorption from the intestine in a time-dependent manner by use of 25Mg2+. In addition, local absorption of Ca2+ and Mg2+ in different segments of the intestine of mice was determined by using surgically implanted intestinal cannulas. By these methods, it was demonstrated that intestinal absorption of Mg2+ is regulated by dietary needs in a vitamin D-independent manner. Also, it was shown that at low luminal concentrations, favoring transcellular absorption, Ca2+ transport mainly takes place in the proximal segments of the intestine, whereas Mg2+ absorption predominantly occurs in the distal part of the gastrointestinal tract. Vitamin D treatment of mice increased serum Mg2+ levels and 24-h urinary Mg2+ excretion, but not intestinal absorption of 25Mg2+. Segmental cannulation of the intestine and time-dependent absorption studies using 25Mg2+ provide new ways to study intestinal Mg2+ absorption.

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