Vitamin K deficiency reduces testosterone production in the testis through down-regulation of the Cyp11a a cholesterol side chain cleavage enzyme in rats

Shirakawa, Hitoshi; Ohsaki, Yusuke; Minegishi, Yuji; Takumi, Naofumi; Ohinata, Kousaku; Furukawa, Yuji; Mizutani, Takeo; Komai, Michio

doi:10.1016/j.bbagen.2006.05.008

Cited by 54 publications

(41 citation statements)

References 41 publications

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“…In this experiment, the V.K concentration in the diet was not deficient but from normal to 3 times the normal. Therefore, our result is not contradictory to the result of the previous report ( 24 ).…”

Section: Discussioncontrasting

confidence: 56%

“…Though the principal functions of V.K are blood coagulation and bone formation ( 23 ), it was reported that V.K was involved in steroid production through the regulation of Cyp11a, which is a rate-limiting enzyme in testosterone synthesis ( 24 ). V.K deficiency diet decreased the plasma testosterone concentration and the expression of Cyp11a expression of testis; but no differences in plasma testosterone concentration or Cyp11a expression between the normal-V.K diet and the high-V.K diet, 10 times the normal-V.K diet, were shown ( 24 ). In this experiment, the V.K concentration in the diet was not deficient but from normal to 3 times the normal.…”

Section: Discussionmentioning

confidence: 99%

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The Interactive Effect of Dietary Fat-Soluble Vitamin Levels on the Depression of Gonadal Development in Growing Male Rats Kept under Disturbed Daily Rhythm

Hanai

Esashi²

2011

J Nutr Sci Vitaminol

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SummaryThe purpose of this study was to clarify the effects of nutrients on the gonadal development of male rats kept under constant darkness as a model of disturbed daily rhythm. In the present study we examined fat-soluble vitamins and their interactions in this test population. Four fat-soluble vitamins (vitamin A (V.A), vitamin D (V.D), vitamin E (V.E) and vitamin K (V.K)) were selected as experimental factors, and the dietary content of these vitamins was normal (AIN-93G) or three times the normal content. Lighting conditions (constant darkness or normal lighting) were also added as a factor. Four-week-old rats (Fischer 344 strain) were kept under constant darkness or normal lighting (12-h light/dark cycle) for 4 wk. The lighting condition and V.E, and the interactions between the lighting condition and V.E and between V.A and V.D were observed to affect the testes and epididymides weights. There was an influence of the lighting condition only on the seminal vesicles and prostate weights and the serum testosterone concentration. Among the constant darkness groups (D-groups), the highest value for testes weight was observed under the normal-V.A, normal-V.D and high-V.E diet. The interaction between lighting condition and V.E showed the testes weight increased slightly in response to changing to a high-V.E diet from a normal-V.E diet under normal lighting (N-group) but was greatly increased in response to this change in the D-group. It became clear that the amount of dietary V.E necessary for the gonadal development of rats increases when rats are kept under constant darkness. Key Words constant darkness, disturbed daily rhythm, gonad, fat soluble vitamin, orthogonal arrayThe number of people who are living under disturbed daily rhythm has been increasing due to the globalization of business and social activities, and diversification of the forms of labor. Such irregularities in daily rhythm adversely affect bio-regulatory mechanisms, resulting in an abnormal diurnal rhythm that can impede biological activities structurally and functionally. The process by which such disorders are induced is, in theory, dependent upon the nutritional condition of the individual. However, there are no basic data on the nutritional aspects of maintaining or promoting health under the condition of disturbed daily rhythm. Metabolic function changes under a condition of disturbed daily rhythm such as constant darkness, and it can be presumed that nutritional requirements in such an environment change, as well. The perspective behind this research is as follows: as basic data on the relationship between nutritional status and gonadal development in rats with disturbed daily rhythm accumulate, these data can be used for human research, and finally, dietary reference intakes can be compiled for persons living under disturbed daily rhythm.Lighting is one of the key external factors for the formation of daily rhythm. Rats kept under constant darkness develop disturbances in their feeding and motoractivity rhythms, and suffer from alter...

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Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

The Interactive Effect of Dietary Fat-Soluble Vitamin Levels on the Depression of Gonadal Development in Growing Male Rats Kept under Disturbed Daily Rhythm

Hanai

Esashi²

2011

J Nutr Sci Vitaminol

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“…Four micrograms of total RNA from the liver was used as the template for cDNA synthesis, as described previously. 16) An aliquot of synthesized cDNA was used as the template for quantitative PCR that was carried out using an Applied Biosystems 7300 sequence detection system (Foster City, CA, USA). The cDNAs of glucose-6-phosphatase (G6PC) and other genes were amplified by using cDNA-specific primers (shown in Table 1) in SYBR Premix Ex Taq (Takara Bio, Shiga, Japan).…”

Section: Methodsmentioning

confidence: 99%

Effect of Biotin Treatment on Hepatic Gene Expression in Streptozotocin-Induced Diabetic Rats

Sugita

Shirakawa

Sugimoto

et al. 2008

Bioscience, Biotechnology, and Biochemistry

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“…The mRNA level of Cyp11a positively correlated with MK-4 concentration in the testis. Moreover, testosterone levels in the plasma and testis of vitamin K-deficient rats were significantly reduced, in spite of normal levels of plasma LH [25]. Another study further described the effects of dietary vitamin K on testosterone production.…”

Section: Mk-4 Enhances Steroidogenesis By Activating Pkamentioning

confidence: 86%

Menaquinone‐4 Enhances Steroidogenesis in Testis Derived Tumor Cells Via the Elevation of cAMP Level

Ho¹,

Shirakawa²,

Komai³

2017

Vitamin K2 - Vital for Health and Wellbeing

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Naturally existing vitamin K consists of vitamins K1 and K2. Menaquinone-4 (MK-4), an analog of vitamin K2 and a product of vitamin K1 metabolism, can be detected in several organs, including the testis; however, the function of MK-4 in these tissues has not been well characterized. Recent studies have suggested that vitamin K is involved in enhancing protein kinase A (PKA) activity in several cell types, thus regulating numerous PKA-dependent biological processes. To highlight the effect of vitamin K, we focused on its role in the steroidogenic pathway. Experiments on vitamin K-deficient rats revealed a reduced expression of genes involved in the biosynthesis of cholesterol and steroid hormones in the testis. Moreover, compared with control animals, rats fed on MK-4 diet presented significantly higher testosterone levels in the plasma and testis. These results suggest that vitamin K is involved in the steroidogenic pathway in the testis. Testosterone levels were found to increase in a dose-dependent manner also in cell-based experiments upon addition of MK-4, but such an effect was not observed in vitamin K1 levels. Furthermore, the effect of MK-4 on testosterone production was abolished by the specific PKA inhibitor H89, thus confirming the regulatory role of MK-4 on PKA activation. Here, we describe how MK-4 modulates PKA activation by enhancing intracellular 3′,5′-cyclic adenosine monophosphate (cAMP) levels in testisderived I-10 cells. The presented evidence supports the role of MK-4 in cAMP/PKA signaling and steroidogenesis.

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Vitamin K deficiency reduces testosterone production in the testis through down-regulation of the Cyp11a a cholesterol side chain cleavage enzyme in rats

Cited by 54 publications

References 41 publications

The Interactive Effect of Dietary Fat-Soluble Vitamin Levels on the Depression of Gonadal Development in Growing Male Rats Kept under Disturbed Daily Rhythm

The Interactive Effect of Dietary Fat-Soluble Vitamin Levels on the Depression of Gonadal Development in Growing Male Rats Kept under Disturbed Daily Rhythm

Effect of Biotin Treatment on Hepatic Gene Expression in Streptozotocin-Induced Diabetic Rats

Menaquinone‐4 Enhances Steroidogenesis in Testis Derived Tumor Cells Via the Elevation of cAMP Level

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