25-hydroxyvitamin D(3)-1alpha-hydroxylase expression in normal and pathological parathyroid glands
(2002) In The Journal of clinical endocrinology and metabolism 87(6). p.72-2967- Abstract
Active vitamin D, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], plays a pivotal role in calcium homeostasis and bone metabolism. Circulating levels of 1,25(OH)(2)D(3) are thought to be dependent mainly on the activity of the renal cytochrome P450 enzyme 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-hydroxylase), which is potently induced by PTH. However, 1alpha-hydroxylase activity or expression has also been reported at several extrarenal sites, at which local synthesis of 1,25(OH)(2)D(3) appears to fulfill autocrine or paracrine functions. This includes tissues such as placenta and brain that also express LRP-2/megalin, an endocytic receptor for multiple ligands, which is involved in the renal uptake of the substrate for 1alpha... (More)
Active vitamin D, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], plays a pivotal role in calcium homeostasis and bone metabolism. Circulating levels of 1,25(OH)(2)D(3) are thought to be dependent mainly on the activity of the renal cytochrome P450 enzyme 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-hydroxylase), which is potently induced by PTH. However, 1alpha-hydroxylase activity or expression has also been reported at several extrarenal sites, at which local synthesis of 1,25(OH)(2)D(3) appears to fulfill autocrine or paracrine functions. This includes tissues such as placenta and brain that also express LRP-2/megalin, an endocytic receptor for multiple ligands, which is involved in the renal uptake of the substrate for 1alpha -hydroxylase, 25-hydroxyvitamin D(3). We have previously demonstrated LRP-2/megalin in parathyroid cells, and here we present results from RT-PCR and immunohistochemical analyses showing coincident expression of 1alpha-hydroxylase in normal and pathological parathyroid tissue. With real-time quantitative RT-PCR analysis, the expression of 1alpha-hydroxylase mRNA was higher in the majority of parathyroid adenomas and secondary hyperplastic glands but lower in parathyroid carcinomas, compared with normal parathyroid tissue. The findings imply that in addition to feedback control by circulating 1,25(OH)(2)D(3) levels, parathyroid cells may also be influenced by local 1alpha -hydroxylase activity with possible growth regulatory and differentiating effects.
(Less)
- author
- Segersten, Ulrika ; Correa, Pamela LU ; Hewison, Martin ; Hellman, Per ; Dralle, Henning ; Carling, Tobias ; Akerström, Göran and Westin, Gunnar
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics, Adenoma/metabolism, Aged, Humans, Hyperparathyroidism/metabolism, Hyperparathyroidism, Secondary/metabolism, Middle Aged, Parathyroid Diseases/metabolism, Parathyroid Glands/metabolism, Parathyroid Neoplasms/metabolism, RNA, Messenger/metabolism, Reference Values
- in
- The Journal of clinical endocrinology and metabolism
- volume
- 87
- issue
- 6
- pages
- 72 - 2967
- publisher
- Oxford University Press
- external identifiers
-
- pmid:12050281
- scopus:0036075861
- ISSN
- 0021-972X
- DOI
- 10.1210/jcem.87.6.8604
- language
- English
- LU publication?
- no
- id
- 74f81d75-9859-40b7-a691-51a21647900b
- date added to LUP
- 2021-11-29 11:15:27
- date last changed
- 2024-03-08 23:19:11
@article{74f81d75-9859-40b7-a691-51a21647900b,
abstract = {{<p>Active vitamin D, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], plays a pivotal role in calcium homeostasis and bone metabolism. Circulating levels of 1,25(OH)(2)D(3) are thought to be dependent mainly on the activity of the renal cytochrome P450 enzyme 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-hydroxylase), which is potently induced by PTH. However, 1alpha-hydroxylase activity or expression has also been reported at several extrarenal sites, at which local synthesis of 1,25(OH)(2)D(3) appears to fulfill autocrine or paracrine functions. This includes tissues such as placenta and brain that also express LRP-2/megalin, an endocytic receptor for multiple ligands, which is involved in the renal uptake of the substrate for 1alpha -hydroxylase, 25-hydroxyvitamin D(3). We have previously demonstrated LRP-2/megalin in parathyroid cells, and here we present results from RT-PCR and immunohistochemical analyses showing coincident expression of 1alpha-hydroxylase in normal and pathological parathyroid tissue. With real-time quantitative RT-PCR analysis, the expression of 1alpha-hydroxylase mRNA was higher in the majority of parathyroid adenomas and secondary hyperplastic glands but lower in parathyroid carcinomas, compared with normal parathyroid tissue. The findings imply that in addition to feedback control by circulating 1,25(OH)(2)D(3) levels, parathyroid cells may also be influenced by local 1alpha -hydroxylase activity with possible growth regulatory and differentiating effects.</p>}},
author = {{Segersten, Ulrika and Correa, Pamela and Hewison, Martin and Hellman, Per and Dralle, Henning and Carling, Tobias and Akerström, Göran and Westin, Gunnar}},
issn = {{0021-972X}},
keywords = {{25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics; Adenoma/metabolism; Aged; Humans; Hyperparathyroidism/metabolism; Hyperparathyroidism, Secondary/metabolism; Middle Aged; Parathyroid Diseases/metabolism; Parathyroid Glands/metabolism; Parathyroid Neoplasms/metabolism; RNA, Messenger/metabolism; Reference Values}},
language = {{eng}},
number = {{6}},
pages = {{72--2967}},
publisher = {{Oxford University Press}},
series = {{The Journal of clinical endocrinology and metabolism}},
title = {{25-hydroxyvitamin D(3)-1alpha-hydroxylase expression in normal and pathological parathyroid glands}},
url = {{http://dx.doi.org/10.1210/jcem.87.6.8604}},
doi = {{10.1210/jcem.87.6.8604}},
volume = {{87}},
year = {{2002}},
}