Homologous Up-Regulation of Vitamin D Receptors Is Tissue Specific in the Rat

Gensure, Robert C.; Antrobus, Steve D.; Fox, John; Okwueze, Martina I.; Talton, Stephanie Y.; Walters, Marian R.

doi:10.1359/jbmr.1998.13.3.454

Cited by 18 publications

(8 citation statements)

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“…Alkaline phosphatase comprises a family of specific isoenzymes, the activity of which is associated with the differentiated phenotype of enterocytes and colonocytes (42,43); calbindin-9k is one of the best documented biological markers of the hormonal action of 1,25-(OH) 2 D 3 at the genomic level (44 -46). The present results indicate that, in addition to modulation of VDR expression, in vivo exposure to estrogen markedly enhances the response of markers of VDR activity in the duodenal mucosa to endogenous 1,25-(OH) 2 D. Neither serum 1,25-(OH) 2 D nor PTH concentrations were altered by estrogen repletion; thus, we may conclude that the increase in intestinal VDR expression and activity was directly related to estrogen and is unlikely the result of an indirect effect of estrogen via PTH or 1,25-(OH) 2 D on VDR expression (48,49).…”

Section: Discussionmentioning

confidence: 97%

Estrogen Increases 1,25-Dihydroxyvitamin D Receptors Expression and Bioresponse in the Rat Duodenal Mucosa

Liel

1999

Endocrinology

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Menopause and estrogen deficiency are associated with apparent intestinal resistance to vitamin D, which can be reversed by estrogen replacement. The in vivo influence of estrogens on duodenal vitamin D receptor (VDR) was studied in three groups of rats: ovariectomized (OVX), sham-operated, and ovariectomized rats treated daily with estrogen (40 g/kg BW) for 2 weeks (OVX ϩ E). Estrogen administration to OVX rats resulted in a 2-fold increase in VDR messenger RNA transcripts. 1,25(OH) 2 D 3 was shown to bind specifically to one class of receptors in duodenal mucosal extracts, with a dissociation constant of 0.03 nM. Binding was significantly increased in duodenal extracts from OVX ϩ E rats, compared with OVX rats (735 Ϯ 81 vs. 295 Ϯ 26 fmol/mg protein; P Ͻ 0.001); a comparable, 1.5-to 2-fold increase in VDR protein expression was observed in Western blot analyzes of the duodenal mucosa. Markers of VDR activity were increased in estrogen-exposed rats: calbindin-9k messenger RNA transcript content was 1.4-to 1.6-fold higher, and alkaline phosphatase activity was 1.4-to 3-fold higher in sham-operated and OVX ϩ E, respectively, compared with OVX. 25(OH)D, 1,25(OH) 2 D, or PTH levels were not altered by estrogen treatment. Cumulatively, these findings suggest that estrogen up-regulates VDR expression in the duodenal mucosa and concurrently increases the responsiveness to endogenous 1,25(OH) 2 D. Modulation of intestinal VDR activity by estrogen, and subsequent influence on intestinal calcium absorption, could be one of the major protective mechanisms of estrogen against osteoporosis. (Endocrinology 140: 280 -285, 1999) I NTESTINAL calcium absorption takes place via two main mechanisms: passive diffusion, which occurs when luminal calcium is high; and active absorption, a complex and not fully understood process mediated by 1,25(OH) 2 D 3 , which predominates when luminal calcium is low (1). Under physiological circumstances, 1,25(OH) 2 D 3 is primarily produced in the kidneys under the influence of PTH stimulation. PTH secretion, in turn, is dependent on extracellular free calcium concentration, as sensed by calcium-sensing-receptors located in parathyroid cells' membranes (2). Overall, the rate of active intestinal calcium absorption is determined by physiologic interactions between various components of the PTH-vitamin D-endocrine system organized in a multilevel negative feed-back loop structure.Intestinal calcium absorption declines with age, both in humans (3, 4) and in rats (5). A widely held hypothesis suggests that the decrease in intestinal calcium absorption results from a sequence of events initiated by low estrogen levels, causing increased bone resorption; released calcium increases extracellular space calcium concentration, which suppresses PTH secretion, followed by a subsequent decrease in 1,25(OH) 2 D 3 production and in 1,25(OH) 2 D 3 plasma concentration, and finally results in decreased intestinal calcium absorption (6).Nevertheless, there is evidence that estrogen may be more directly i...

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Section: Discussionmentioning

confidence: 97%

Estrogen Increases 1,25-Dihydroxyvitamin D Receptors Expression and Bioresponse in the Rat Duodenal Mucosa

Liel

1999

Endocrinology

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“…Upregulation of Vdr also occurred in kidney of CVD rats 1 day after a single 100 ng dose of 1,25(OH) 2 D 3 , but no changes were seen in intestine, testis, or lung. Following infusion of 1,25(OH) 2 D 3 into KVD rats that were kept normocalcemic, the renal Vdr was upregulated, but testicular Vdr levels were again unaffected (Gensure et al 1998). This shows that Vdr expression is regulated differently in the kidney and testis.…”

Section: Regulation Of Testicular Vd Metabolism and Putative Downstrementioning

confidence: 95%

Vitamin D metabolism, sex hormones, and male reproductive function

Jensen¹

2012

Reproduction

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The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function. The VD receptor (VDR) and the VD metabolizing enzyme expression studies documented the presence of this system in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both systemic and local VD metabolism may influence male reproductive function. However, it is still debated which cell is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses mechanistic and association studies conducted in animals and humans. The reviewed evidence suggests some effects of VD on estrogen and testosterone biosynthesis and implicates involvement of both systemic and local VD metabolism in the regulation of male fertility potential.

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“…Sertoli cells of different species express a VDR; however, the molecular mechanisms of 1,25(OH) 2 -D 3 actions on these cells remain unclear [28][29][30][31][32]. Here, we used patch-clamp electrophysiology to investigate 1,25(OH) 2 -D 3 modulation of membrane electric processes underlying secretory activities in mouse TM4 immature Sertoli cells.…”

Section: Introductionmentioning

confidence: 99%