Vitamin D metabolism, sex hormones, and male reproductive function

THE-DET-OAK

IncreasedMyT @ ULV
Abstract

The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function. The VD receptor (VDR) and the VD metabolizing enzyme expression studies documented the presence of this system in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both systemic and local VD metabolism may influence male reproductive function. However, it is still debated which cell is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses mechanistic and association studies conducted in animals and humans. The reviewed evidence suggests some effects of VD on estrogen and testosterone biosynthesis and implicates involvement of both systemic and local VD metabolism in the regulation of male fertility potential.


Perspectives

From animal and human studies, it is evident that VD is important for optimal male reproductive function. Some of the VD effects are presumably mediated locally by the presence of VDR and the VD metabolizing enzymes in adult male germ cells, Leydig cells, and male reproductive tract, while other actions may be influenced by the systemic effects of VD serum levels. The low expression of VDR and VD metabolizing enzymes in spermatozoa from infertile men compared with normal men supports a role for the local VD metabolism and may have functional consequences. Especially, as 1,25(OH)2D3 mediates a nongenomic increase in intracellular calcium concentration, which seems to be important for sperm function especially following capacitation in the female reproductive tract. Most of the VD effects in the testes appear to be mediated through estrogen biosynthesis, but other candidate genes involved in calcium homeostasis, endocrine function, and cell cycle control may be involved. An association between serum 25-OHD3 and testosterone production remains to be proven, although it is plausible that the declining serum VD levels with age may be involved in the age-related loss of function of both gonads and bone, but further studies are needed to determine causality. Moreover, both local VD metabolism and serum levels of 25-OHD3 may have a direct effect on sperm motility in both animal and humans even after considering the indirect effect mediated by calcium homeostasis. The effects on sperm motility may be mediated mainly in epididymis rather than the testes, but further studies are needed to determine the exact site and mechanisms of action and to investigate whether supplementation of cholecalciferol improves semen quality in VD-deficient men.

http://www.reproduction-online.org/content/144/2/135.full
 
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