Here is an excerpt from this article. This is some HARDCORE scientific research and a GREAT POST....!
Now if I could just figure out what a "Knockout Mouse" is... ? LOL
Really though, the SIMPLE ANECDOTAL observation is that I FEEL DAMN GOOD when I am catchin some rays. I tend to be thinner, feel better, and sleep well. It would also be an interesting experiment to find out the relationship as to the health of people who spend time in the sun as it relates to CHILLIN, Working outdoors, and the amount of skin exposed. At first I would think you would need to factor in a VANITY co-efficient, but the goodness of the sun just appears to be AUTOMATIC in MANY ways... Its almost like - you dont have to, but YOU WILL CONFORM to health in the light of the SUN... Really makes sense as GENETICALLY - We are founded by it....
And there weren't no clothes or no roofs when the code was first built...
VD regulates biosynthesis of estradiol and
testosteroneNumerous studies investigated the putative physiological
relationship between circulating levels of
25OHD3/1,25(OH)2D, the activity of VDR and VD
metabolizing enzymes, and serum testosterone and
estradiol levels in both animals and humans (Tanaka
et al. 1976, Hyldstrup et al. 1984, Small et al. 1984,
Hochberg et al. 1985, Krabbe et al. 1986, Sonnenberg
et al. 1986, Hagenfeldt et al. 1992, Morley et al. 1993,
Inpanbutr et al. 1996, Zofkova & Kancheva 1996,
Otremski et al. 1997, Rapado et al. 1999, Kinuta et al.
2000, van Abel et al. 2002, Braga et al. 2002,
Van Cromphaut et al. 2003, Echchgadda et al. 2004,
Valimaki et al. 2004, Kastelan et al. 2009, Fleet &
Schoch 2010, Krishnan et al. 2010a, 2010b, Meng et al.
2010, Pilz et al. 2011, Ramlau-Hansen et al. 2010,Wehr
et al. 2010, Ceglia et al. 2011, Foresta et al. 2011,
Lundqvist et al. 2011, Lee et al. 2012). It has been shown
that estrogen promotes the two-step activation of
cholecalciferol to 1,25(OH)2D3 and reinforces a positive
effect on calcium homeostasis through a direct stimulatory
effect on intestinal calcium absorption. Testosterone
is also a stimulator of calcium absorption in
prepubertal boys, but studies in mice show that androgens
increase calcium excretion by inhibiting expression of
renal calcium transport proteins (Fleet & Schoch 2010,
Hsu et al. 2010).
Regulation of aromatase (CYP19A1) and estrogen
production by VD has been extensively studied in tissueand
cell lines from breast, adipose tissue, bone, and
gonads (Krishnan et al. 2010a, 2010b). 1,25(OH)2D3 is a
known regulator of aromatase expression (Bouillon et al.
2008, Haussler et al. 2011), but the effect is tissue
specific due to activity of different promoters (1.3,1.4,II)
in various tissues. 1,25(OH)2D3 mediates transcriptional
repression of aromatase expression in breast, in contrast
to a modest gonadal induction (ovary) and a high
induction in bone (Krishnan et al. 2010b). The proposed
tissue-specific regulation is in line with an earlier study
showing lower aromatase expression in testis and
epididymis concomitant with lower serum estrogen
and elevated gonadotropins in Vdr KO mice compared
with wild-type animals (Kinuta et al. 2000). Interestingly,
the reduced serum estrogen level was reversible
following calcium supplementation, indicating that at
least part of the impaired gonadal aromatase expression
was due to hypocalcemia. In contrast, the elevated LH
level persisted and may therefore depend on additional
factors besides calcium imbalance (Kinuta et al.
2000). A recent study supported the tissue-specific
1,25(OH)2D3-mediated regulation of aromatase
expression using three different cell lines. Besides
tissue-specific regulation of aromatase, they also found
that 1,25(OH)2D3 induced androgen production in
Figure 4 CYP24A1 expression in human spermatozoa. Semen sample
from a man from the general population with sperm concentration:
123 million/ml and 87% motile sperm. 85% of his spermatozoa are
expressing CYP24A1 at the annulus (left). Semen sample from a man
part of an infertile couple with sperm concentration: 6 million/ml
and 50% motile sperm. This man has 0% expressing CYP24A1 at the
annulus (right). Arrowhead indicates annulus and arrows indicate
expression at the neck. Bar corresponds to 10 mm. Figure reproduced
from Blomberg Jensen M, Jørgensen A, Nielsen JE, Leffers H,
Andersen AN, Skakkebaek NE, Juul A, Rajpert-De-Meyts E &
Jørgensen N 2012 Expression of the vitamin D metabolizing enzyme
CYP24A1 at the annulus of human spermatozoa may serve as a
novel marker of semen quality. International Journal of Andrology.
By permission of John Wiley and Sons.
Vitamin D and male reproduction 141
Reproduction, a high quality journal publishing research into the cellular and molecular biology of reproduction Reproduction (2012) 144 135–152
breast and prostate but caused an opposite effect in
adrenal cells (Lundqvist et al. 2011).
It is noteworthy that the observed in vitro effects
seemed less pronounced in vivo as VD-deficient
chickens had higher (although not significantly) serum
testosterone levels than controls, despite that VD
deficiency caused low calbindin expression in the
Leydig cells (Inpanbutr et al. 1996). However, another
study found low serum testosterone in VD-deficient rats,
which increased to normal values following supplementation
of 1,25(OH)2D3 (Sonnenberg et al. 1986).
Importantly, a small human study conducted on boys
younger than 18 years with VD-resistant rickets
(no functional VDR) showed that the sensitivity to LH
was not affected by VD, as serum testosterone concentration
after hCG stimulation (hCG test) was normal
(Hochberg et al. 1985). Several human studies (Table 1)
have investigated the relationship between 25-OHD3 or
1,25(OH)2D3 and testosterone production. A direct
comparison of these selected studies is not advisable
because the cohorts differ greatly in size, age, comorbidities,
median 25-OHD3 level, and the use of relevant
confounders such as time of blood sampling, serum LH,
calcium, etc. The positive associations between serum
25-OHD3 and testosterone/free androgen index (FAI) are
mainly reported in men above 40 years of age, with a
median BMI above 25 and presence of comorbidities
such as metabolic syndrome, diabetes, or cardiovascular
disease. By contrast, in younger healthy men, serum
levels of 25-OHD3 were either not associated or
negatively associated with testosterone and FAI, while
serum 25-OHD3 was positively associated with SHBG
(Valimaki et al. 2004, Ramlau-Hansen et al. 2011).
Other studies have shown that both serum 25-OHD3 and
testosterone levels decline with age, while gonadotropins
and SHBG increase. The age-related alterations
may be of clinical importance and probably partly
responsible for the increased risk of osteoporosis with
age (van Abel et al. 2006, Giovannucci et al. 2006,
Kaplan et al. 2006, Bischoff-Ferrari 2008, van Schoor
et al. 2008, Ross 2011, Lee et al. 2012). Simple
associations do not prove causality but may rather
reflect other imbalances as indicated in a large study
examining 1340 men aged 76 years or older. Here, total
testosterone inversely correlated with serum phosphorous,
while calcium levels were positively correlated with
PTH (Meng et al. 2010).
Accumulating evidence suggests a complex interplay
between bone, gonadal function, calcium absorption
and excretion, glucose metabolism, and pituitary
function (Fukumoto & Martin 2009, Hwang et al.
2011, Oury et al. 2011, Pi et al. 2011): sex hormones
regulate calcium absorption, bone formation, and
insulin production; VD stimulates calcium absorption,
bone formation, estrogen and insulin production; and
bone markers such as osteocalcin stimulate testosterone
and insulin production. The complicated relationship
must be taken into account when investigating associations
between VD and sex hormones, and it is not
advisable to extrapolate from simple associations
between two factors, because the disturbance or
imbalance in a selected organ may be fully or partly
compensated by various mechanisms; for instance, low
serum VD levels by calcium mobilization due to
elevated PTH secretion. Such compensation may be
decreasing with age, which could explain the positive
associations reported in older men with comorbidities,
but further studies are needed to clarify this. New
association studies should therefore address the relationship
between sex hormones and VD levels by including
additional factors such as calcium, PTH, phosphate, LH,
estrogen, and optimally also BMD, osteocalcin, IGF1,
FGF23, body fat percentage, and glucose metabolism to
determine causal associations that can be subsequently
used as endpoints for validation in randomized clinical
trials (RCT).
Most of the association studies investigating VD and
testosterone stratified their cohort in tertiles or quartiles.
This can be appropriate, but the conclusions drawn may
be limited, in particular when 25-OHD3 serum level is
the explanatory variable. VD has the highest impact on
most organs in the concentration range from undetectable
to 50 nM (20 ng/ml), while most of the effects are
stable when serum 25-OHD3 levels exceed 75–100 nM
(Dawson-Hughes et al. 2005, Lips 2006, Lips et al.
2010). Thus, the clinical relevance is reduced when the
median VD concentration in the cohort is high, as an
increase in serum 25-OHD3 level from 80 to 90 nM is
unlikely to have any major physiological effect. Recently,
a large association study showed a dose–response
relationship between 25-OHD3 and testosterone. It
was comparable to the effects observed between VD
and PTH secretion or calcium absorption, because it was
strong in the lower range of the serum 25-OHD3 scale
and leveled off above 50–80 nM (Nimptsch et al. 2012).
This could be due to a direct effect of VD progenitors on
the Leydig cells, although it could also be secondary to
changes in calcium homeostasis caused by VD deficiency
(Bouillon et al. 2008). Unfortunately, this study was
limited by the low proportion of VD-deficient men, thus
precluding investigation of associations at the very low
end of 25-OHD3 levels (!25 nmol/l), where the effect
presumably would be larger. Moreover, most of the
studies reporting a positive association between VD
and total testosterone/FAI are limited by an age effect
(Table 1). Men with high 25-OHD3 serum concentrations
are generally younger and have a higher
testosterone level than men with low 25-OHD3. The
age difference between each quartile is more than 1 year
in the large association study investigating more than
2000 men referred for coronary angiography, and a
similar age trend was found from the lowest to the
highest VD quintile in a recent association study (Wehr
et al. 2010, Nimptsch et al. 2012). Although most studies
142 M Blomberg Jensen
Reproduction (2012) 144 135–152 Reproduction, a high quality journal publishing research into the cellular and molecular biology of reproduction
adjust their analyses for age, they are not adjusted for the
frequency of comorbidities such as impaired bone
health, glucose metabolism, kidney function, calcium
absorption, etc., that follows with increasing age. This
concern was corroborated by a recent association study
including more than 3000 elderly men (Lee et al. 2012).
The authors found the same positive associations
between 25-OHD3 serum level and testosterone/FAI,
but after adjusting for health and lifestyle factors,
no significant associations were observed between
25-OHD3 and any of the reproductive hormones.
However, the putative positive effect of VD on
testosterone production was supported by a small RCT,
which showed increasing testosterone following VD
supplementation (average 48 years). The clinical value
is limited by the design of the study as they mainly
tested the effect of weight loss. Moreover, the causal
factor is not obvious despite that the increase in
testosterone was 2.7 nM in cholecalciferol-treated
men vs 0.9 nM in the control group (Pilz et al. 2011).
In conclusion, sufficient data exist to claim that VD is
a strong regulator of aromatase expression and may
be involved in regulation of steroidogenesis in human
Leydig cells, but so far, there is not enough evidence for
a stimulatory effect of VD on testicular testosterone
production
Now if I could just figure out what a "Knockout Mouse" is... ? LOL
Really though, the SIMPLE ANECDOTAL observation is that I FEEL DAMN GOOD when I am catchin some rays. I tend to be thinner, feel better, and sleep well. It would also be an interesting experiment to find out the relationship as to the health of people who spend time in the sun as it relates to CHILLIN, Working outdoors, and the amount of skin exposed. At first I would think you would need to factor in a VANITY co-efficient, but the goodness of the sun just appears to be AUTOMATIC in MANY ways... Its almost like - you dont have to, but YOU WILL CONFORM to health in the light of the SUN... Really makes sense as GENETICALLY - We are founded by it....
And there weren't no clothes or no roofs when the code was first built...VD regulates biosynthesis of estradiol and
testosteroneNumerous studies investigated the putative physiological
relationship between circulating levels of
25OHD3/1,25(OH)2D, the activity of VDR and VD
metabolizing enzymes, and serum testosterone and
estradiol levels in both animals and humans (Tanaka
et al. 1976, Hyldstrup et al. 1984, Small et al. 1984,
Hochberg et al. 1985, Krabbe et al. 1986, Sonnenberg
et al. 1986, Hagenfeldt et al. 1992, Morley et al. 1993,
Inpanbutr et al. 1996, Zofkova & Kancheva 1996,
Otremski et al. 1997, Rapado et al. 1999, Kinuta et al.
2000, van Abel et al. 2002, Braga et al. 2002,
Van Cromphaut et al. 2003, Echchgadda et al. 2004,
Valimaki et al. 2004, Kastelan et al. 2009, Fleet &
Schoch 2010, Krishnan et al. 2010a, 2010b, Meng et al.
2010, Pilz et al. 2011, Ramlau-Hansen et al. 2010,Wehr
et al. 2010, Ceglia et al. 2011, Foresta et al. 2011,
Lundqvist et al. 2011, Lee et al. 2012). It has been shown
that estrogen promotes the two-step activation of
cholecalciferol to 1,25(OH)2D3 and reinforces a positive
effect on calcium homeostasis through a direct stimulatory
effect on intestinal calcium absorption. Testosterone
is also a stimulator of calcium absorption in
prepubertal boys, but studies in mice show that androgens
increase calcium excretion by inhibiting expression of
renal calcium transport proteins (Fleet & Schoch 2010,
Hsu et al. 2010).
Regulation of aromatase (CYP19A1) and estrogen
production by VD has been extensively studied in tissueand
cell lines from breast, adipose tissue, bone, and
gonads (Krishnan et al. 2010a, 2010b). 1,25(OH)2D3 is a
known regulator of aromatase expression (Bouillon et al.
2008, Haussler et al. 2011), but the effect is tissue
specific due to activity of different promoters (1.3,1.4,II)
in various tissues. 1,25(OH)2D3 mediates transcriptional
repression of aromatase expression in breast, in contrast
to a modest gonadal induction (ovary) and a high
induction in bone (Krishnan et al. 2010b). The proposed
tissue-specific regulation is in line with an earlier study
showing lower aromatase expression in testis and
epididymis concomitant with lower serum estrogen
and elevated gonadotropins in Vdr KO mice compared
with wild-type animals (Kinuta et al. 2000). Interestingly,
the reduced serum estrogen level was reversible
following calcium supplementation, indicating that at
least part of the impaired gonadal aromatase expression
was due to hypocalcemia. In contrast, the elevated LH
level persisted and may therefore depend on additional
factors besides calcium imbalance (Kinuta et al.
2000). A recent study supported the tissue-specific
1,25(OH)2D3-mediated regulation of aromatase
expression using three different cell lines. Besides
tissue-specific regulation of aromatase, they also found
that 1,25(OH)2D3 induced androgen production in
Figure 4 CYP24A1 expression in human spermatozoa. Semen sample
from a man from the general population with sperm concentration:
123 million/ml and 87% motile sperm. 85% of his spermatozoa are
expressing CYP24A1 at the annulus (left). Semen sample from a man
part of an infertile couple with sperm concentration: 6 million/ml
and 50% motile sperm. This man has 0% expressing CYP24A1 at the
annulus (right). Arrowhead indicates annulus and arrows indicate
expression at the neck. Bar corresponds to 10 mm. Figure reproduced
from Blomberg Jensen M, Jørgensen A, Nielsen JE, Leffers H,
Andersen AN, Skakkebaek NE, Juul A, Rajpert-De-Meyts E &
Jørgensen N 2012 Expression of the vitamin D metabolizing enzyme
CYP24A1 at the annulus of human spermatozoa may serve as a
novel marker of semen quality. International Journal of Andrology.
By permission of John Wiley and Sons.
Vitamin D and male reproduction 141
Reproduction, a high quality journal publishing research into the cellular and molecular biology of reproduction Reproduction (2012) 144 135–152
breast and prostate but caused an opposite effect in
adrenal cells (Lundqvist et al. 2011).
It is noteworthy that the observed in vitro effects
seemed less pronounced in vivo as VD-deficient
chickens had higher (although not significantly) serum
testosterone levels than controls, despite that VD
deficiency caused low calbindin expression in the
Leydig cells (Inpanbutr et al. 1996). However, another
study found low serum testosterone in VD-deficient rats,
which increased to normal values following supplementation
of 1,25(OH)2D3 (Sonnenberg et al. 1986).
Importantly, a small human study conducted on boys
younger than 18 years with VD-resistant rickets
(no functional VDR) showed that the sensitivity to LH
was not affected by VD, as serum testosterone concentration
after hCG stimulation (hCG test) was normal
(Hochberg et al. 1985). Several human studies (Table 1)
have investigated the relationship between 25-OHD3 or
1,25(OH)2D3 and testosterone production. A direct
comparison of these selected studies is not advisable
because the cohorts differ greatly in size, age, comorbidities,
median 25-OHD3 level, and the use of relevant
confounders such as time of blood sampling, serum LH,
calcium, etc. The positive associations between serum
25-OHD3 and testosterone/free androgen index (FAI) are
mainly reported in men above 40 years of age, with a
median BMI above 25 and presence of comorbidities
such as metabolic syndrome, diabetes, or cardiovascular
disease. By contrast, in younger healthy men, serum
levels of 25-OHD3 were either not associated or
negatively associated with testosterone and FAI, while
serum 25-OHD3 was positively associated with SHBG
(Valimaki et al. 2004, Ramlau-Hansen et al. 2011).
Other studies have shown that both serum 25-OHD3 and
testosterone levels decline with age, while gonadotropins
and SHBG increase. The age-related alterations
may be of clinical importance and probably partly
responsible for the increased risk of osteoporosis with
age (van Abel et al. 2006, Giovannucci et al. 2006,
Kaplan et al. 2006, Bischoff-Ferrari 2008, van Schoor
et al. 2008, Ross 2011, Lee et al. 2012). Simple
associations do not prove causality but may rather
reflect other imbalances as indicated in a large study
examining 1340 men aged 76 years or older. Here, total
testosterone inversely correlated with serum phosphorous,
while calcium levels were positively correlated with
PTH (Meng et al. 2010).
Accumulating evidence suggests a complex interplay
between bone, gonadal function, calcium absorption
and excretion, glucose metabolism, and pituitary
function (Fukumoto & Martin 2009, Hwang et al.
2011, Oury et al. 2011, Pi et al. 2011): sex hormones
regulate calcium absorption, bone formation, and
insulin production; VD stimulates calcium absorption,
bone formation, estrogen and insulin production; and
bone markers such as osteocalcin stimulate testosterone
and insulin production. The complicated relationship
must be taken into account when investigating associations
between VD and sex hormones, and it is not
advisable to extrapolate from simple associations
between two factors, because the disturbance or
imbalance in a selected organ may be fully or partly
compensated by various mechanisms; for instance, low
serum VD levels by calcium mobilization due to
elevated PTH secretion. Such compensation may be
decreasing with age, which could explain the positive
associations reported in older men with comorbidities,
but further studies are needed to clarify this. New
association studies should therefore address the relationship
between sex hormones and VD levels by including
additional factors such as calcium, PTH, phosphate, LH,
estrogen, and optimally also BMD, osteocalcin, IGF1,
FGF23, body fat percentage, and glucose metabolism to
determine causal associations that can be subsequently
used as endpoints for validation in randomized clinical
trials (RCT).
Most of the association studies investigating VD and
testosterone stratified their cohort in tertiles or quartiles.
This can be appropriate, but the conclusions drawn may
be limited, in particular when 25-OHD3 serum level is
the explanatory variable. VD has the highest impact on
most organs in the concentration range from undetectable
to 50 nM (20 ng/ml), while most of the effects are
stable when serum 25-OHD3 levels exceed 75–100 nM
(Dawson-Hughes et al. 2005, Lips 2006, Lips et al.
2010). Thus, the clinical relevance is reduced when the
median VD concentration in the cohort is high, as an
increase in serum 25-OHD3 level from 80 to 90 nM is
unlikely to have any major physiological effect. Recently,
a large association study showed a dose–response
relationship between 25-OHD3 and testosterone. It
was comparable to the effects observed between VD
and PTH secretion or calcium absorption, because it was
strong in the lower range of the serum 25-OHD3 scale
and leveled off above 50–80 nM (Nimptsch et al. 2012).
This could be due to a direct effect of VD progenitors on
the Leydig cells, although it could also be secondary to
changes in calcium homeostasis caused by VD deficiency
(Bouillon et al. 2008). Unfortunately, this study was
limited by the low proportion of VD-deficient men, thus
precluding investigation of associations at the very low
end of 25-OHD3 levels (!25 nmol/l), where the effect
presumably would be larger. Moreover, most of the
studies reporting a positive association between VD
and total testosterone/FAI are limited by an age effect
(Table 1). Men with high 25-OHD3 serum concentrations
are generally younger and have a higher
testosterone level than men with low 25-OHD3. The
age difference between each quartile is more than 1 year
in the large association study investigating more than
2000 men referred for coronary angiography, and a
similar age trend was found from the lowest to the
highest VD quintile in a recent association study (Wehr
et al. 2010, Nimptsch et al. 2012). Although most studies
142 M Blomberg Jensen
Reproduction (2012) 144 135–152 Reproduction, a high quality journal publishing research into the cellular and molecular biology of reproduction
adjust their analyses for age, they are not adjusted for the
frequency of comorbidities such as impaired bone
health, glucose metabolism, kidney function, calcium
absorption, etc., that follows with increasing age. This
concern was corroborated by a recent association study
including more than 3000 elderly men (Lee et al. 2012).
The authors found the same positive associations
between 25-OHD3 serum level and testosterone/FAI,
but after adjusting for health and lifestyle factors,
no significant associations were observed between
25-OHD3 and any of the reproductive hormones.
However, the putative positive effect of VD on
testosterone production was supported by a small RCT,
which showed increasing testosterone following VD
supplementation (average 48 years). The clinical value
is limited by the design of the study as they mainly
tested the effect of weight loss. Moreover, the causal
factor is not obvious despite that the increase in
testosterone was 2.7 nM in cholecalciferol-treated
men vs 0.9 nM in the control group (Pilz et al. 2011).
In conclusion, sufficient data exist to claim that VD is
a strong regulator of aromatase expression and may
be involved in regulation of steroidogenesis in human
Leydig cells, but so far, there is not enough evidence for
a stimulatory effect of VD on testicular testosterone
production
)] OR Should he get really pissed now.. But then again, Democratic, capitalist, or FREEDOM, is in fact socialism in disguise.
