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Increased 25-hydroxyvitamin D3 1α-hydroxylase and reduced 25-hydroxyvitamin D3 24-hydroxylase expression in parathyroid tumors: new prospects for treatment of hyperparathyroidism with vitamin D
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. (Endocrine Surgery)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
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2002 (Engelska)Ingår i: Journal of Clinical Endocrinology & Metabolism, ISSN 0021-972X, Vol. 87, nr 12, s. 5826-5829Artikel i tidskrift (Refereegranskat) Published
Ort, förlag, år, upplaga, sidor
2002. Vol. 87, nr 12, s. 5826-5829
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-93560OAI: oai:DiVA.org:uu-93560DiVA, id: diva2:167080
Tillgänglig från: 2005-10-17 Skapad: 2005-10-17 Senast uppdaterad: 2015-06-16Bibliografiskt granskad
Ingår i avhandling
1. Vitamin D Hydroxylating Enzymes and Analogues in Parathyroid Tumors and Breast Cancer
Öppna denna publikation i ny flik eller fönster >>Vitamin D Hydroxylating Enzymes and Analogues in Parathyroid Tumors and Breast Cancer
2005 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

In hyperparathyroidism (HPT) raised serum concentrations of ionized calcium is caused by increased secretion of parathyroid hormone (PTH) by parathyroid tumors. Active vitamin D, 1α,25-dihydroxyvitamin D3, is known to suppress PTH secretion and to reduce proliferation of parathyroid tumor cells.

The aim of this thesis was to examine expression of vitamin D hydroxylating enzymes, regulating the activation and inactivation of vitamin D and to study effects of vitamin D analogues, in parathyroid tumors and breast cancer.

The vitamin D activating enzyme, CYP27B1/25-hydroxyvitamin D3 1α-hydroxylase (1α-hydroxylase) and the vitamin D inactivating enzyme CYP24A1/25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase) were expressed in parathyroid tumors and breast cancer.

The parathyroid tumors had raised expression levels of 1α-hydroxylase and reduced levels of 24-hydroxylase in comparison to normal parathyroid glands, indicating ability for endogenous activation of vitamin D. The expression of 1α-hydroxylase may be of therapeutic advantage for local activation of non-1α-hydroxylated vitamin D analogues in tumor cells, thereby reducing unwanted hypercalcemic effects.

Three of five selected low calcemic vitamin D analogues had as efficient PTH suppressing effect, in bovine parathyroid cells, as three vitamin D analogues used clinically for treatment of secondary HPT.

The non-1α-hydroxylated vitamin D analogue EB1285 showed antiproliferative and PTH suppressive effects as well as transcriptional activity in parathyroid and breast tumor cells, respectively.

Ketoconazole, an inhibitor of vitamin D hydroxylating enzymes, suppressed PTH secretion and potentiated the effect of vitamin D analogues. Combined treatment with vitamin D analogues and specific 24-hydroxylase inhibitors may be important for future therapy.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2005. s. 59
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 78
Nyckelord
Surgery, hyperparathyroidism, breast cancer, vitamin D, CYP27B1, CYP24A1, vitamin D analogues, ketoconazole, vitamin D receptor, Kirurgi
Nationell ämneskategori
Kirurgi
Forskningsämne
kirurgi
Identifikatorer
urn:nbn:se:uu:diva-6008 (URN)91-554-6361-4 (ISBN)
Disputation
2005-11-08, Rosénsalen, Kvinnokliniken, Akademiska sjukhuset ing 95, Uppsala, 09:15
Opponent
Handledare
Tillgänglig från: 2005-10-17 Skapad: 2005-10-17Bibliografiskt granskad

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Segersten, UlrikaHellman, PerÅkerström, GöranWestin, Gunnar

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