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Investigating the effect of testosterone by itself and in combination with letrozole on 1,25-dihydroxy vitamin D and FGF23 in male rats

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Abstract

Background

Testosterone deficiency might be associated with vitamin D levels in hypogonadal men, but it is not clear whether testosterone can affect vitamin D and fibroblast growth factor-23 (FGF23), either directly or indirectly via aromatization to estradiol. We aimed to investigate the role of testosterone on vitamin D metabolism and serum FGF23 in male rats.

Methods

A total of 48 male rats were divided into 4 equal groups: sham; O, orchiectomy; O + T, orchiectomized rats treated with testosterone; and O + T + L, orchiectomized rats treated with combination of testosterone and letrozole. We compare the vitamin D metabolism biochemical parameters in these four groups, before and after the study.

Results

We detected a significant reduction in 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (DBP), FGF23, and 1,25-dihydroxyvitamin D (1,25(OH)2D) serum level in O group compared to sham group (p = 0.004, p = 0.009, p < 0.001 and p < 0.001, respectively), and a significant increase in serum phosphorus, parathyroid hormone (PTH), and alkaline phosphatase (ALP) levels in orchiectomized rats in comparison to sham group (p < 0.001, p = 0.022, and p = 0.006, respectively). However, these changes were corrected by testosterone replacement in O + T and O + T + L groups. In addition, we found that DBP and 1,25(OH)2D serum levels were significantly higher in O + T group in comparison to O + T + L group (p = 0.030 and p = 0.026, respectively).

Conclusions

Testosterone plays a significant role on regulating 25(OH)D, DBP, FGF23, phosphate (Phos), PTH, and 1,25(OH)2D serum levels in male rats. Also, testosterone has a potent effect on 1,25(OH)2D and DBP by its conversion to estradiol.

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Acknowledgements

The authors wish to thank Mr. H. Argasi at the Research Consultation Center (RCC) at Shiraz University of Medical Sciences for his invaluable assistance in editing this manuscript.

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Authors and Affiliations

  1. Shiraz Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, P.O. Box: 71345-1744, Shiraz, Iran

    F. Saki, S. R. Kasaee, F. Sadeghian, F. Koohpeyma & GH. R. Omrani

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  1. F. Saki
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  2. S. R. Kasaee
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Correspondence to GH. R. Omrani.

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Conflict of interest

Gholamhossein Ranjbar Omrani, Seyed Reza Kasaee, Farhad Koohpeima and Forough Saki declare that they have no conflict of interest.

Ethical approval

The local ethics committee of the Shiraz University of Medical Sciences and vice-chancellor of research at SUMS approved this study with ID:95-01-01-12923. The experiment was conducted in accordance with the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines on the use and care of research animals. All procedures were approved by the local ethic and experimentation committee of Shiraz university of Medical Sciences.

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Saki, F., Kasaee, S.R., Sadeghian, F. et al. Investigating the effect of testosterone by itself and in combination with letrozole on 1,25-dihydroxy vitamin D and FGF23 in male rats. J Endocrinol Invest 42, 19–25 (2019). https://doi.org/10.1007/s40618-018-0875-3

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