Effects of endogenous estrogen on renal calcium and phosphate handling in elderly women

Dick, Ian M.; Devine, Amanda; Beilby, John; Prince, Richard

doi:10.1152/ajpendo.00140.2004

Cited by 47 publications

(32 citation statements)

References 31 publications

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“…Several works have described that estrogens can downregulate the kidney sodium-phosphate cotransporter (Na-Pi), increasing phosphorus in urine and causing hypophosphatemia. 17,38,39 In agreement with this view, we found that estrogen administration significantly decreased serum phosphorus levels to values similar to the CKD-control group ( Figure 3B). Because phospho- BASIC RESEARCH www.jasn.org rus is well known to increase the synthesis and secretion of PTH, 40 the reduction of phosphorus, secondary to the use of estrogens, could have been at least partly responsible for the reduction in PTH levels.…”

Section: Discussionsupporting

confidence: 86%

Indirect Regulation of PTH by Estrogens May Require FGF23

Carrillo-López

Román-García

Rodríguez-Rebollar

et al. 2009

Journal of the American Society of Nephrology

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The mechanisms by which estrogens modulate PTH are controversial, including whether or not estrogen receptors (ERs) are present in the parathyroid glands. To explore these mechanisms, we combined a rat model of CKD with ovariectomy and exogenous administration of estrogens. We found that estrogen treatment significantly decreased PTH mRNA and serum levels. We did not observe ER␣ or ER␤ mRNA or protein in the parathyroids, suggesting an indirect action of estrogens on PTH regulation. Estrogen treatment significantly decreased serum 1,25(OH) 2 vitamin D 3 and phosphorus levels. In addition, estrogens significantly increased fibroblast growth factor 23 (FGF23) mRNA and serum levels. In vitro, estrogens led to transcriptional and translational upregulation of FGF23 in osteoblast-like cells in a timeand concentration-dependent manner. These results suggest that estrogens regulate PTH indirectly, possibly through FGF23. 20: 200920: -201720: , 200920: . doi: 10.1681 Estrogen deficiency is the main factor implicated in bone loss in postmenopausal osteoporosis. 1 As a consequence of the lack of estrogens, bone turnover increases, leading to an imbalance between bone formation and bone resorption, favoring the latter. 2,3 This imbalance affects calcium-phosphate metabolism and may increase serum parathyroid hormone (PTH) levels. 4 Estrogen replacement therapy prevents bone loss and fractures, 5,6 acting directly on bone cells through their specific estrogen receptors (ERs): ␣ and ␤. 7,8 In addition, in postmenopausal women, estrogens can also reduce PTH serum levels 4,9 through an as of yet poorly understood mechanism. J Am Soc NephrolA possible direct effect of estrogens reducing PTH acting through ER␣ and ER␤ located in the parathyroid cells has been suggested, but the existence of ER␣ and ER␤ in parathyroid tissue is still a controversial issue. 10 -13 Estrogens may also decrease PTH secretion by acting on other factors such as calcium, 14,15 1,25(OH) 2 D 3 (calcitriol), 15 and phosphorus, 16,17 among others. Recently, fibroblast growth factor 23 (FGF23), involved in phosphorus and vitamin D metabolism, 18 has been suggested to influence PTH synthesis and secretion. 19 In women with chronic kidney disease (CKD), little is known about the role that estrogen deficiency plays in the pathogenesis and progression of bone disease. 20,21 Understanding the mechanism through which estrogens act on PTH is also a subject of interest in these patients, because of the high prevalence of secondary parathyroid disorders. 22 Because several aspects of the effects of estrogens on PTH remain unclear, the objective of this study was to investigate the factors and mechanisms involved in the likely effect of estrogens on the parathyroid gland.

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Section: Discussionsupporting

confidence: 86%

Indirect Regulation of PTH by Estrogens May Require FGF23

Carrillo-López

Román-García

Rodríguez-Rebollar

et al. 2009

Journal of the American Society of Nephrology

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“…Both estrogens and PTHrP are known to affect renal calcium handling, although most data suggest that they act in opposite directions. Estrogen deficiency in postmenopausal women has been shown to be associated with higher rates of urinary calcium excretion, and replacement of estrogens in this setting usually results in a reduction in urinary calcium (37)(38)(39). PTH and PTHrP are known to act on the PTHR1 in the distal tubule to reduce fractional calcium excretion (40,41).…”

Section: Discussionmentioning

confidence: 99%

Increased PTHrP and Decreased Estrogens Alter Bone Turnover but Do Not Reproduce the Full Effects of Lactation on the Skeleton

et al. 2010

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During lactation, calcium is mobilized from the maternal skeleton to supply the breast for milk production. This results in rapid but fully reversible bone loss. Prior studies have suggested that PTHrP, secreted from the breast, and estrogen deficiency, due to suckling-induced central hypogonadism, combine to trigger bone resorption. To determine whether this combination was sufficient to explain bone loss during lactation, we raised PTHrP levels and decreased levels of estrogens in nulliparous mice. PTHrP was infused via osmotic minipumps and estrogens were decreased either by using leuprolide, a long-acting GnRH agonist, or by surgical ovariectomy (OVX). Bone mineral density declined by 23.2 ± 1.3% in the spine and 16.8 ± 1.9% in the femur over 10 d of lactation. This was accompanied by changes in trabecular architecture and an increase in both osteoblast and osteoclast numbers. OVX and PTHrP infusion both induced a modest decline in bone mineral density over 10 d, but leuprolide treatment did not. The combination of OVX and PTHrP was more effective than either treatment alone, but there was no interaction between PTHrP and leuprolide. None of the treatments reproduced the same degree of bone loss caused by lactation. However, both forms of estrogen deficiency led to an increase in osteoclasts, whereas infusion of PTHrP increased both osteoblasts and osteoclasts. Therefore, although the combination of PTHrP and estrogen deficiency contributes to bone loss, it is insufficient to reproduce the full response of the skeleton to lactation, suggesting that other factors also regulate bone metabolism during this period.

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“…There is some evidence that estrogen may have direct effects on kidneys, besides those on bone [41]. It has been shown that, in elderly women, estrogen deficiency may exacerbate bone resorption by increasing renal calcium loss [42]. A reduced effect of estrogen on renal calcium metabolism could be relevant in CF patients, who appear to be at higher risk for nephrocalcinosis and urolithiasis [43,44].…”

Section: Discussionmentioning

confidence: 99%