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Direct effects of vitamin D3 analogues on G-protein mediated signalling systems in rat osteosarcoma cells and rat pituitary adenoma cells

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Abstract

In normal rats treated with 1,25(OH)2D3 or 24,25(OH)2D3, serum Ca2+, ALP, PRL and GH are significantly altered. In order to study the primary effect of vitamin D3 analogues on target organ function, rat UMR 106 osteosarcoma and GH3 pituitary adenoma cells in monolayer culture were exposed accordingly.

Surprisingly, prolonged exposure of these cell lines to physiological levels of either 1,25(OH)2D3 or 24,25(OH)2D3 did not significantly affect the secretory parameters (ALP, PRL or GH) tested. However, 1,25(OH)2D3 exposure significantly reduced PTH- and Gpp(NH)p-elicited AC as well as Gpp(NH)p-stimulated PLC activities in the UMR 106 cells. These changes were accompanied by an increase and decrease in the membrane contents of the G-protein subunits G36β and Gq/11α, respectively. In contrast, 24,25(OH)2D3 remained without significant biological effect on these signalling systems despite concomitantly augmented levels of G36β. TRH- and Gpp(NH)p-elicited PLC activities in the GH3 cells were significantly reduced by 1,25(OH)2D3 with a concurrent reduction in cellular amounts of Gq/11α, however, 24,25(OH)2D3 did not significantly alter any signalling systems nor G-proteins analyzed.

It is concluded that the osteoblastic and pituitary cell secretion of ALP, PRL and GH remain unaffected by the presence of 1,25(OH)2D3 and 24,25(OH)2D3, despite distinct alterations in components of G-protein mediated signalling pathways. Hence, other factors like ambient Ca2+ may be responsible for the perturbed secretory patterns of ALP and PRL seen in vitamin D3 treated rats.

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Abbreviations

AC:

adenylate cyclase

ALP:

alkaline phosphatase

BGP:

osteocalcin

BSA:

bovine serum albumin

DA:

dopamine

DAG:

diacylglycerol

GH:

growth hormone

GHRH:

growth hormone releasing hormone

Gpp(NH)p:

guanosine 5′-[βγ-imido]triphosphate

G-protein:

guanine nucleotide-binding regulatory protein

Gsα etc.:

Gs protein α-subunit

IP3 :

inositol 1,4,5 trisphosphate

OAF:

osteoclast activating factor

PGE2 :

prostaglandin E2

PKA & PKC:

protein kinase A & C

PLC:

phospholipase C

PRL:

prolactin

PTH:

parathyroid hormone

SRIF:

somatostatin

TRH:

thyrotropin releasing hormone

VIP:

vasoactive intestinal peptide

25(OH)D3 :

25 hydroxy vitamin D3

1,25(OH)2D3 :

1·25 dihydroxy vitamin D3

24,25(OH)2D3 :

24,25 dihydroxy vitamin D3

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Authors and Affiliations

  1. Institute of Medical Biochemistry, University of Oslo, Oslo, Norway

    Berit M. Mortensen, Hanne W. Lund, Greg Jablonski, Ruth H. Paulssen & Jan O. Gordeladze

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  1. Berit M. Mortensen
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  2. Hanne W. Lund
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  3. Greg Jablonski
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  4. Ruth H. Paulssen
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  5. Jan O. Gordeladze
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Mortensen, B.M., Lund, H.W., Jablonski, G. et al. Direct effects of vitamin D3 analogues on G-protein mediated signalling systems in rat osteosarcoma cells and rat pituitary adenoma cells. Biosci Rep 15, 135–150 (1995). https://doi.org/10.1007/BF01207454

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