[OA] Vitamin D Receptor Rs2228570 Polymorphism Is Associated with LH Levels in Men Exposed to Anabolic Androgenic Steroids
It is generally known that the use of anabolic androgenic steroids (AAS) suppresses the secretion of the pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH). This effect results from a negative feedback of androgens on the hypothalamic-pituitary–gonadal (HPG) axis. We recently showed that already a single dose of intra-muscular administration of testosterone or nandrolone suppresses the secretion of LH and FSH, but with large inter-individual variations.
After discontinuation of AAS use, LH and FSH may be suppressed for a long period of time, resulting in anabolic steroid induced hypogonadism (ASIH). The time of AAS induced hypogonadotropic hypogonadism is highly variable and is dependent on the duration, dose and type of steroids used, co-use of other drugs and age, but may also be influenced by genetic factors.
Several studies have shown that vitamin D deficiency is associated with low testosterone levels in men which may be accompanied by low levels of gonadotropins. Vitamin D exhibits its effect by binding to the vitamin D receptor (VDR). A previous study reported that a single nucleotide polymorphism (SNP) rs731236 (also known as TaqI) in VDR was associated with serum LH concentration but not with FSH concentrations in women with polycystic ovarian syndrome (PCOS). This polymorphism is a silent T > C SNP located in exon 9 and affects the function of VDR, probably due to an altered expression profile.
The VDR genotype rs2228570 (also known as Fok1) is a C > T non-synonymous polymorphism situated in the translation start site of VDR. The C variant results in a truncated protein, 3 amino acids shorter, with higher activity. Studies have shown that carriers of the T variant, expressing a VDR-protein with lower activity, are more susceptible to different cancer forms, including ovarian cancer and have an impaired immune system. However, this SNP has never been studied in relation to LH and FSH concentrations.
The primary aim of this study was to investigate the association between the vitamin D receptor polymorphisms rs2228570 (Fok1) and rs731236 (TaqI) and LH and FSH levels in relation to anabolic androgenic steroid (AAS) use. To this end post hoc analysis of material from two previous performed studies were used.
Two cohorts were analyzed.
· Cohort 1 comprised healthy volunteers given single supra-physiological doses of 500 mg testosterone (n = 25).
· Cohort 2 comprised 45 self-reporting AAS users.
Healthy volunteers homozygous for the C-allele of the Fok1 polymorphism exhibited 30% higher LH levels than T-carriers at baseline (p = 0.04) and twice the levels 14 days after testosterone administration (p = 0.01). AAS users homozygous for the C-allele had four times higher LH levels than TT-individuals (p < 0.05).
FSH levels were not associated with Fok1 polymorphism, nor were LH and FSH levels associated with the TaqI polymorphism.
In conclusion, there is an association between LH levels and the Fok1 VDR polymorphism and this difference is even more pronounced in AAS users and subjects with suppressed LH levels.
Bjorkhem-Bergman L, Lehtihet M, Rane A, Ekstrom L. Vitamin D receptor rs2228570 polymorphism is associated with LH levels in men exposed to anabolic androgenic steroids. BMC research notes 2018;11:51. Vitamin D receptor rs2228570 polymorphism is associated with LH levels in men exposed to anabolic androgenic steroids
It is generally known that the use of anabolic androgenic steroids (AAS) suppresses the secretion of the pituitary luteinizing hormone (LH) and follicle stimulating hormone (FSH). This effect results from a negative feedback of androgens on the hypothalamic-pituitary–gonadal (HPG) axis. We recently showed that already a single dose of intra-muscular administration of testosterone or nandrolone suppresses the secretion of LH and FSH, but with large inter-individual variations.
After discontinuation of AAS use, LH and FSH may be suppressed for a long period of time, resulting in anabolic steroid induced hypogonadism (ASIH). The time of AAS induced hypogonadotropic hypogonadism is highly variable and is dependent on the duration, dose and type of steroids used, co-use of other drugs and age, but may also be influenced by genetic factors.
Several studies have shown that vitamin D deficiency is associated with low testosterone levels in men which may be accompanied by low levels of gonadotropins. Vitamin D exhibits its effect by binding to the vitamin D receptor (VDR). A previous study reported that a single nucleotide polymorphism (SNP) rs731236 (also known as TaqI) in VDR was associated with serum LH concentration but not with FSH concentrations in women with polycystic ovarian syndrome (PCOS). This polymorphism is a silent T > C SNP located in exon 9 and affects the function of VDR, probably due to an altered expression profile.
The VDR genotype rs2228570 (also known as Fok1) is a C > T non-synonymous polymorphism situated in the translation start site of VDR. The C variant results in a truncated protein, 3 amino acids shorter, with higher activity. Studies have shown that carriers of the T variant, expressing a VDR-protein with lower activity, are more susceptible to different cancer forms, including ovarian cancer and have an impaired immune system. However, this SNP has never been studied in relation to LH and FSH concentrations.
The primary aim of this study was to investigate the association between the vitamin D receptor polymorphisms rs2228570 (Fok1) and rs731236 (TaqI) and LH and FSH levels in relation to anabolic androgenic steroid (AAS) use. To this end post hoc analysis of material from two previous performed studies were used.
Two cohorts were analyzed.
· Cohort 1 comprised healthy volunteers given single supra-physiological doses of 500 mg testosterone (n = 25).
· Cohort 2 comprised 45 self-reporting AAS users.
Healthy volunteers homozygous for the C-allele of the Fok1 polymorphism exhibited 30% higher LH levels than T-carriers at baseline (p = 0.04) and twice the levels 14 days after testosterone administration (p = 0.01). AAS users homozygous for the C-allele had four times higher LH levels than TT-individuals (p < 0.05).
FSH levels were not associated with Fok1 polymorphism, nor were LH and FSH levels associated with the TaqI polymorphism.
In conclusion, there is an association between LH levels and the Fok1 VDR polymorphism and this difference is even more pronounced in AAS users and subjects with suppressed LH levels.
Bjorkhem-Bergman L, Lehtihet M, Rane A, Ekstrom L. Vitamin D receptor rs2228570 polymorphism is associated with LH levels in men exposed to anabolic androgenic steroids. BMC research notes 2018;11:51. Vitamin D receptor rs2228570 polymorphism is associated with LH levels in men exposed to anabolic androgenic steroids
