Investigating the effect of testosterone by itself and in combination with letrozole on 1,25-dihydroxy vitamin D and FGF23 in male rats
- 93 Downloads
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.
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.
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).
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.
KeywordsTestosterone FGF23 DBP 1,25(OH)2D
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.
There is no financial support.
Compliance with ethical standards
Conflict of interest
Gholamhossein Ranjbar Omrani, Seyed Reza Kasaee, Farhad Koohpeima and Forough Saki declare that they have no conflict of interest.
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.
For this type of study formal consent is not required.
- 3.Baserga R, Hongo A, Rubini M, Prisco M, Valentinis B (1997) The IGF-I receptor in cell growth, transformation and apoptosis. Biochim Biophys Acta (BBA) Rev Cancer 1332(3):F105–F126Google Scholar
- 7.Kamelian T, Saki F, Jeddi M, Dabbaghmanesh M, Omrani G (2017) Effect of Cholecalciferol therapy on serum FGF23 in vitamin D deficient patients: a randomized clinical trial. J Endocrinol Investig 1–8Google Scholar
- 15.Bolland MJ, Grey AB, Ames RW, Horne AM, Mason BH, Wattie DJ, Gamble GD, Bouillon R, Reid IR (2007) Age-, gender-, and weight-related effects on levels of 25-hydroxyvitamin D are not mediated by vitamin D binding protein. Clin Endocrinol 67(2):259–264Google Scholar
- 22.Nimptsch K, Platz EA, Willett WC, Giovannucci E (2012) Association between plasma 25-OH vitamin D and testosterone levels in men. Clin Endocrinol 77(1):106–112Google Scholar
- 27.Heydarpour F, Amini B, Kalantari S, Rostami A, Heydarpour P (2007) Determination of sensitivity of male Wistar rats to an equal dose of ketamine/xylazine injection at anesthetic dose in a chronic model of hypernatremia in comparison with control group. Saudi Med J 28(10):1485–1488PubMedGoogle Scholar
- 41.Kolek OI, Hines ER, Jones MD, LeSueur LK, Lipko MA, Kiela PR, Collins JF, Haussler MR, Ghishan FK (2005) 1α, 25-dihydroxyvitamin D3 upregulates FGF23 gene expression in bone: the final link in a renal-gastrointestinal-skeletal axis that controls phosphate transport. Am J Physiol Gastrointest Liver Physiol 289(6):G1036–G1042PubMedGoogle Scholar
- 42.Barthel TK, Mathern DR, Whitfield GK, Haussler CA, Hopper HA, Hsieh J-C, Slater SA, Hsieh G, Kaczmarska M, Jurutka PW (2007) 1, 25-Dihydroxyvitamin D 3/VDR-mediated induction of FGF23 as well as transcriptional control of other bone anabolic and catabolic genes that orchestrate the regulation of phosphate and calcium mineral metabolism. J Steroid Biochem Mol Biol 103(3):381–388PubMedGoogle Scholar