Vitamin D and sex steroid production in men with normal or impaired Leydig cell function
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Vitamin D and sex steroid production in men with normal or impaired Leydig cell function. / Holt, Rune; Juel Mortensen, Li; Harpelunde Poulsen, Katrine; Nielsen, John Erik; Frederiksen, Hanne; Jørgensen, Niels; Jørgensen, Anne; Juul, Anders; Blomberg Jensen, Martin.
I: The Journal of Steroid Biochemistry and Molecular Biology, Bind 199, 105589, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Vitamin D and sex steroid production in men with normal or impaired Leydig cell function
AU - Holt, Rune
AU - Juel Mortensen, Li
AU - Harpelunde Poulsen, Katrine
AU - Nielsen, John Erik
AU - Frederiksen, Hanne
AU - Jørgensen, Niels
AU - Jørgensen, Anne
AU - Juul, Anders
AU - Blomberg Jensen, Martin
N1 - Copyright © 2020 Elsevier Ltd. All rights reserved.
PY - 2020
Y1 - 2020
N2 - Production of testosterone is under tight control by human chorion gonadotropin (hCG) during fetal life and luteinizing hormone (LH) in adulthood. Several animal and human studies have linked vitamin D status with sex steroid production although it is not clear whether there exist a direct or indirect involvement in androgen production. Few studies have investigated this crosslink in young healthy men and putative direct or synergistic effect of activated vitamin D (1,25(OH)2D3) and LH/hCG on sex steroid production in vitro. Here, we present cross-sectional data from 300 young men and 41 hCG-stimulated men with impaired Leydig cell function combined with data from an ex vivo culture of human testicular tissue exposed to 1,25(OH)2D3 alone or in combination with hCG. Serum 25-OHD was positively associated with SHBG (β:0.002; p = 0.023) and testosterone/estradiol-ratio (β:0.001; p = 0.039), and inversely associated with free testosterone (%) (free testosterone/total testosterone) (β:-0.002; p = 0.016) in young men. Vitamin D deficient men had higher total and free estradiol concentrations than men with higher vitamin D status (19% and 18%, respectively; p < 0.01). Interestingly, men with impaired Leydig cell function and vitamin D deficiency had a significantly lower hCG-mediated increase in total and free testosterone compared with vitamin D sufficient men (p < 0.05). Accordingly, testicular tissue exposed to 100 nM 1,25(OH)2D3 had a 15% higher testosterone release into the media compared with vehicle treated specimens (p = 0.030). In conclusion, vitamin D deficiency is associated with lower testosterone/estradiol ratio in young men and lower Leydig cell sensitivity after hCG-stimulation in men with impaired gonadal function. The significant effect of 1,25(OH)2D3 on testosterone production in a human testis model supports that the stimulatory effect at least in part may be direct. Larger placebo-controlled studies are needed to determine whether vitamin D supplementation can influence testosterone production.
AB - Production of testosterone is under tight control by human chorion gonadotropin (hCG) during fetal life and luteinizing hormone (LH) in adulthood. Several animal and human studies have linked vitamin D status with sex steroid production although it is not clear whether there exist a direct or indirect involvement in androgen production. Few studies have investigated this crosslink in young healthy men and putative direct or synergistic effect of activated vitamin D (1,25(OH)2D3) and LH/hCG on sex steroid production in vitro. Here, we present cross-sectional data from 300 young men and 41 hCG-stimulated men with impaired Leydig cell function combined with data from an ex vivo culture of human testicular tissue exposed to 1,25(OH)2D3 alone or in combination with hCG. Serum 25-OHD was positively associated with SHBG (β:0.002; p = 0.023) and testosterone/estradiol-ratio (β:0.001; p = 0.039), and inversely associated with free testosterone (%) (free testosterone/total testosterone) (β:-0.002; p = 0.016) in young men. Vitamin D deficient men had higher total and free estradiol concentrations than men with higher vitamin D status (19% and 18%, respectively; p < 0.01). Interestingly, men with impaired Leydig cell function and vitamin D deficiency had a significantly lower hCG-mediated increase in total and free testosterone compared with vitamin D sufficient men (p < 0.05). Accordingly, testicular tissue exposed to 100 nM 1,25(OH)2D3 had a 15% higher testosterone release into the media compared with vehicle treated specimens (p = 0.030). In conclusion, vitamin D deficiency is associated with lower testosterone/estradiol ratio in young men and lower Leydig cell sensitivity after hCG-stimulation in men with impaired gonadal function. The significant effect of 1,25(OH)2D3 on testosterone production in a human testis model supports that the stimulatory effect at least in part may be direct. Larger placebo-controlled studies are needed to determine whether vitamin D supplementation can influence testosterone production.
KW - Adult
KW - Androgens/biosynthesis
KW - Animals
KW - Chorionic Gonadotropin/genetics
KW - Estradiol/genetics
KW - Gonadal Steroid Hormones/biosynthesis
KW - Humans
KW - Leydig Cells/metabolism
KW - Luteinizing Hormone/genetics
KW - Male
KW - Testis/growth & development
KW - Testosterone/biosynthesis
KW - Vitamin D/genetics
KW - Vitamin D Deficiency/genetics
KW - Young Adult
U2 - 10.1016/j.jsbmb.2020.105589
DO - 10.1016/j.jsbmb.2020.105589
M3 - Journal article
C2 - 31953167
VL - 199
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
SN - 0960-0760
M1 - 105589
ER -
ID: 259515894