4 new CR papers

[Guest guest]

Hi All,

4 more new CR papers arrived this morning.

In the first, which was previously posted upon before

I could get it posted (a price of slow), the effect of the

yo-yo diet is examined in terms of an environmental

pollutant.

What happens to such pollutants when CR is exercised?

It seems that its accumulation in the fat tissues continues.

Its concentrations in the fat and maybe more important

brain are increased. Use of the non-absorbable fat,

olestra, in the diet was able to result in the reduction

of the levels of the pollutant that had been increased

by CR.

Of possible relevance to CRers concerned about their

levels of pollutant thought to build up in fat tissues

when on CR, may be that the combination of the fat-

reducing Olestra may be especially effective.

See, please the not pdf-available below.

Am J Physiol Gastrointest Liver Physiol. 2004 Oct 28 [Epub ahead

of print]

Effects of Yo-yo Diet, Caloric Restriction, and Olestra on Tissue

Distribution

of Hexachlorobenzene.

Jandacek RJ, N, Liu M, Zheng S, Yang Q, Tso P.

Chlorinated hydrocarbons are lipophilic, toxic, and persistent in the

environment and animal tissues. They enter the body in food and are

stored in

adipose tissue. Loss of body fat through caloric restriction

mobilizes stored

lipophilic xenobiotics and results in distribution to other tissues.

We have

studied the reversibility of this process in mice that followed a

regimen of

body weight cycling. Weight gain was followed by weight loss, a

second gain, and

a second loss ( " yo-yo diet regimen " ). We measured the distribution of

orally

gavaged (14)C-hexachlorobenzene, which is sparingly metabolized. We

found that

weight cycling has different effects in different organs. Continued

weight loss

resulted in a 3-fold increase of (14)C amount and concentration in

the brain.

After weight regain, (14)C in the brain decreased but then increased

again after

a second weight loss. Weight loss resulted in an increase in the

concentration

of (14)C in adipose tissue without changing the total amount in that

tissue.

Weight loss and regain resulted in an increase of (14)C in the liver

that

reflected an increase of fat in the liver. The regimen of weight gain

and loss

was repeated in mice gavaged with (14)C-hexachlorobenzene, with one

group

receiving the non-absorbable fat, olestra, in the diet. Combined

dietary olestra

and caloric restriction caused a 30-fold increase in the rate of

excretion of

(14)C relative to an ad lib diet or a reduced caloric alone. The

distribution of

(14)C into the brain resulting from the restricted diet was reduced

by 50% by

dietary olestra.

PMID: 15513954 [PubMed - as supplied by publisher]

In the second, a pdf-available, CR paper, the studies of Sun and

Zamel

are presented on calcium in dairy products and other sources on

fat and weight in AL and CR conditions, similar to the yo-yo diet,

I suppose. It seems that both calcium sources act to reduce weight

and fat following CR > AL eating of calcium-rich food, but cereal

with calcium

was less effective than dairy, such as milk or yogurt for fat tissue

loss, Fas expression and Fas activity. Uncoupling protein-2

expression was

similarly affected by dairy, not other source of calcium, but this

was

not differential to the calcium source for uncoupling protein-3

espression.

Some vegetarian CRONers may use such a cereal to obtain

their calcium needed to support bone mass.

J Nutr. 2004 Nov;134(11):3054-60.

Calcium and Dairy Products Inhibit Weight and Fat Regain during Ad

Libitum

Consumption Following Energy Restriction in Ap2-Agouti Transgenic

Mice.

Sun X, Zemel MB.

We demonstrated previously that dietary calcium suppression of

calcitriol

reduces adipocyte Ca(2+), suppresses lipogenesis, and increases lipid

utilization during energy restriction. Notably, dairy calcium sources

exert

markedly greater effects. To determine the effects of dietary calcium

and dairy

products on energy partitioning during subsequent refeeding, we

induced obesity

in aP2-agouti transgenic mice with a high-fat/high-sucrose diet, then

restricted

energy intake from a high-calcium (1.3%) diet for 6 wk to induce fat

loss, and

then provided free access to a low-calcium (0.4%) diet or to

high-calcium (1.3%)

diets that utilized either calcium-fortified foods or dairy products

(milk or

yogurt) for 6 wk. Refeeding the low-calcium diet caused the regain of

all weight

and fat, whereas all high-calcium diets reduced fat gain by 55% (P <

0.01). All

high-calcium diets stimulated adipose tissue uncoupling protein

(UCP)2 and

skeletal muscle UCP3 expression (P < 0.001) and slightly increased

core

temperature (P = 0.136), but only the dairy-based diets elicited a

marked

(>10-fold, P < 0.001) increase in skeletal muscle peroxisome

proliferator-activated receptor-alpha expression. All 3 high-calcium

diets

produced significant increases in lipolysis, decreases in fatty acid

synthase

expression and activity, and reduced fat regain (P < 0.03), but the 2

dairy-containing high-calcium diets exerted significantly greater

effects on

regain (P < 0.01). Thus, high-Ca diets elicit a shift in energy

partitioning and

reduction of weight gain during refeeding, with dairy Ca sources

exerting

markedly greater effects.

PMID: 15514275 [PubMed - in process]

In the third, a pdf-available, paper, the level of weight reduction,

which may be comparable to the level of CR, was 12%.

The CR diet was a control for the effects of calcium-

or iron-deficient diets.

While somewhat technical in nature, the discussion of the bone

characteristics seemed of interest for how they may be affected

in CRers.

The details from the Materials and Methods, Results, Discussion and

Table 1 sections relating to CR are given from the pdf below the

Medline abstract below.

J Nutr. 2004 Nov;134(11):3061-7.

Iron deficiency negatively affects vertebrae and femurs of rats

independently of

energy intake and body weight.

Medeiros DM, Stoecker B, Plattner A, Jennings D, Haub M.

The question of whether iron deficiency has direct adverse effects on

vertebral

trabecular bone and long bones was answered by this study. Four

groups of female

weanling rats were fed for 5 wk diets that were 1) control; 2)

calcium

restricted, 1.0 g Ca/kg diet; 3) iron deficient, <8 mg Fe/kg diet; or

4)

control, pair-fed to the iron-deficient group. Whole body and femur

DEXA

analysis revealed that calcium-restricted and iron-deficient rats had

lower bone

mineral density (BMD) and content (BMC) than pair-fed and control

rats. However,

pair-fed rats also had decreased BMD and BMC compared to control

rats. The third

lumbar trabecular bone microarchitecture in both diet-restricted

groups had

decreased bone volume fraction (BV/TV) and trabecular number and

thickness, a

less favorable structural model index, and increased trabecular

separation

compared with the controls and the pair-fed groups as determined by

microcomputer tomography. The control and pair-fed groups did not

differ from

one another, suggesting that iron deficiency and calcium restriction

affected

vertebrae independently of food intake and body weight. Finite

element analysis

revealed lower force to compress the vertebrae and lower stiffness

but greater

von Mises stress in calcium-restricted and iron-deficient groups

compared to the

control and pair-fed groups. Urinary deoxypyridinium crosslinks,

serum

osteocalcin, and cholcalciferol were increased in calcium-restricted

rats

compared to the other 3 groups. Using micro-CT imaging technology,

this study

demonstrated microarchitectural pathology due to iron deficiency upon

vertebral

trabecular bone compared to the control and pair-fed rats, although

not to the

same extent as severe calcium restriction.

PMID: 15514276 [PubMed - in process]

...3 Abbreviations used: 1,25D, 1,25-dihydroxy vitamin D; AAS,

atomic absorp-tion

spectrophotometry; BAPN, beta-aminoproprionitrile; BMC, bone mineral

con-tent;

BMD, bone mineral density; BV, bone volume; DEXA, dual-energy X-ray

absorptiometry; PF, pair-fed; TV, total volume.

...Diets. The basal diets used were formulated after the

recommen-dations

of the American Institute of Nutrition as modified in 1980

(15) with casein contributing 20%, corn oil 5%, sucrose 50%, and

corn starch 15% of the energy-yielding macronutrients. Because

cellulose has rather high levels of contaminating iron, we used 5%

Diets. The basal diets used were formulated after the

recommen-dations

of the American Institute of Nutrition as modified in 1980

(15) with casein contributing 20%, corn oil 5%, sucrose 50%, and

corn starch 15% of the energy-yielding macronutrients. Because

cellulose has rather high levels of contaminating iron, we used 5%

Avicel as a source of fiber. The remainder of the diet consisted of

vitamin and mineral mixes that meet the requirements of growing

rats except as modified by the experimental protocol.

Diet groups were: 1) rats fed a control diet based on the AIN-1980

recommendations (control); 2) rats fed an iron-deficient diet; 3)

rats

fed a calcium-restricted diet; and 4) a group given the control diet

but

pair-fed (PF)3 to the iron-deficient group. The normal diet contained

about 40 mg Fe/kg (716 microM/kg) diet and 0.52% calcium (5.2 g

Ca/kg diet or 0.130 mol/kg). The iron-deficient diet was formulated

to contain 5–8 mg Fe/kg (89 –143 microM/kg) diet. The

calcium-restricted

diet contained 0.1% calcium (1 g Ca/kg diet or 0.025

mol/kg) by weight. Modifications of the diets for each treatment were

primarily in the mineral mix, as we described in detail previously

(11). Calcium and iron concentrations of all diets were verified by

atomic absorption spectrophotometry analysis. For iron, the mean

was 40.1 mg/kg and for calcium, 6.2 g/kg. The iron-deficient diet

contained 7.7 mg Fe/kg and the calcium-restricted diet had 1 g Ca/kg.

The amount of food consumed by the iron-deficient group was

de-termined

daily and an equal amount of control diet was given to the

pair-fed rats.

TABLE 1

Body weight, heart weight, heart:body weight, hematocrit,

serum 1,25 dihydroxycholcalciferol and osteocalcin, and urinary

excretion of deoxypyridinium crosslinks of rats fed control,

calcium-restricted, iron-deficient, and PF diets for 5 wk^1

Variable Control Ca- Fe- PF

Final body weight, g 209 +/- 4.9 a 185 +/- 4.4 b 181 +/- 3.4 b 184

+/- 3.6 b

Heart weight, g 1.01 +/- 0.045 b 1.03 +/- 0.055 b 1.26 +/- 0.057 a

0.91 +/- 0.035 b

Heart:body weight (x10 3 ) 4.8 +/- 0.15 c 5.6 +/- 0.22 b 6.9 +/-

0.35 a 4.9 +/- 0.20 bc

Hematocrit 0.45 +/- 0.008 a 0.43 +/- 0.005 ab 0.24 +/- 0.016 c 0.42

+/- 0.009 b

Serum 1,25-dihydroxycholcalciferol, pmol/L 305 +/- 15.6 a 416 +/- 5.7

b 291 +/- 52.1 a 299 +/- 17.2 a

Serum osteocalcin, g/L 59 +/- 3.7 a 163 +/- 7.2 b 53 +/- 2.9 a 55

+/- 2.9 a

Urinary deoxypyridinium crosslinks, mol/mol creatinine

3 wk 267 +/- 22.1 b 493 +/- 32.7 a 299 +/- 27.0 b 243 +/- 12.8 b

5 wk 344 +/- 19.9 b 501 +/- 45.5 a 421 +/- 33.8 b 373 +/- 20.2 b

1^Values are means +/- SEM, n 8. Means in a row

without a common superscript differ, P 0.05.

...RESULTS

All rats survived the 5-wk study. The final body weights

were lower (P 0.05) for the calcium-restricted, iron-defi-cient,

and pair-fed groups compared with the control group,

but they did not differ from one another (Table 1). Heart

weight and heart:body weight were elevated (P 0.05) in the

iron-deficient group compared to the other groups as expected

because heart weight is a sign of iron deficiency. The heart to

body weight ratio of the calcium-restricted group also was

elevated somewhat relative to the control group. The iron-deficient

group demonstrated anemia as indicated by low he-matocrits,

which differed (P 0.05) from the other 3 groups.

The pair-fed group had slightly lower hematocrits than the

control group.

...DISCUSSION

We previously reported compromised bone biology in rats

fed iron-deficient diets (11,12). However, the dramatic de-

crease in body weight and corresponding decrease in food

intake observed in iron deficiency could contribute to these

changes in bone biology. Severe food restriction in mature and

young rats results in decreased cortical bone area and mineral

content (16,17). Moderate food restriction of 25% results in

decreased mineralization, cortical bone area, and breaking

strength (18). In this study, the iron-deficient rats had changes

in femurs that differed from the pair-fed group. However, in

some measures, the pair-fed group differed from the control

group. For femur measures, such as BMD, BMC, and bone

breakage, the values of the iron-deficient group were decreased

compared to the pair-fed group, but the values of the pair-fed

group were also decreased relative to the control group. This

may suggest that some of the alteration in bone biology of the

iron-deficient rats could be confounded by body weight or food

intake. Similarly, the whole-body BMD at 5 wk revealed a

similar pattern. However, with respect to the L-3 vertebrae, no

such confounding was apparent. The iron-deficient and cal-cium-

restricted groups differed from the control and pair-fed

groups for most measures, and the latter 2 groups generally did

not differ from each other.

The use of micro-CT imaging gave persuasive results that

iron deficiency has a substantial and consistent negative im-pact

upon trabecular bone biology. The indicators presented

suggested that there was an increase in bone porosity and that

the bone in both calcium-restricted and iron-deficient rats

became more rod-like in contrast to the normal plate-like

appearance of bone.

Finite element analysis has been used in engineering fields,

and biomedical applications with respect to bone biomechan-ics

have gained acceptance. Several reports have validated this

technique experimentally (19 –21), including the Scanco

Medical finite element analysis software (22). Finite element

analysis suggested that the force required to compress the

vertebrae was the least for the calcium-restricted group, but

that the iron-deficient group was significantly lower than the

control and pair-fed groups. This is consistent with the femur

data, but this is the first report, to our knowledge, with regard

to iron deficiency and vertebrae strength. The consistency of

the estimates for stiffness and von Mises stresses and the

minimal variation of these measures within each treatment

group gave us confidence in concluding that iron deficiency

has a negative impact upon bone biomechanics. The decrease

in stiffness for the bones of calcium-restricted and iron-defi-cient

rats means they are more compliant than the control and

pair-fed groups, which is common for bones that are less

mineralized (23).

Like our previous study (11), reduced width and area of

cortical bone were apparent in iron-deficient rats. The degree

of reduction was greater in calcium-restricted rats. Malecki et

al. (24) claimed that iron deficiency did not affect the me-chanical

properties of bone in mice but their animals were not

truly iron deficient in that hematocrit levels were normal.

Iron-replete, hypotransferrinemic mutated mice differed

signif-icantly

from those fed an iron-deficient diet. However, the

hematocrit was 0.40 in the iron-deficient mice, which is not

considered physiological anemia. They also used mice and the

current study evaluated rats. On the other hand, Campos et al.

(25) reported that iron-deficient rats had decreased femur

mineralization that was accompanied by increased cortisol and

parathyroid hormone. In humans, serum ferritin levels and

bone density of skulls of young women were significantly

related (26). Recently, dietary iron in postmenopausal

women was reported to be positively associated with in-creased

bone mineral density in those with low to moderate

calcium intakes (27).

Urinary deoxypyridinium crosslinks and serum osteocalcin

were markedly increased in calcium-restricted rats compared

to all other groups, but there were no differences for the

iron-deficient rats. This may suggest a different mechanism for

the changes in bone physical strength and density in the

iron-deficient group. The increased deoxypyridinoline

crosslinks represent bone breakdown and the increased serum

osteoclacin suggests greater bone turnover in the calcium-restricted

rats but not in iron-deficient rats. We also measured

the active form of cholcalciferol,

alpha-1,25-dihydroxycholcalcif-erol,

because the final hydroxylation is iron dependent (28). In

rats fed the calcium-restricted diet, there was an almost 33%

increase in 1,25-dihydroxycholcalciferol compared to the

other 3 groups, which was expected. However, the iron-defi-cient

group had levels similar to those of control and pair-fed

rats, suggesting that iron deficiency did not affect circulating

levels of this form of cholcalciferol.

Type I collagen is an important component of bone. Sev-eral

studies demonstrated that decreased collagen crosslinking

leads to bone pathology. Lysyl oxidase is a copper-containing

enzyme that catalyzes the crosslinking of the epsilon-amino groups of

lysine and hydroxyproline between adjacent collagen fibrils,

thereby increasing the mechanical strength of the protein.

Copper deficiency was shown to result in decreased breaking

strength in femurs of rats (11). Jonas et al. (29) reported that

femurs from copper-deficient rats had decreased maximal

torque, angular distortion, and toughness compared to pair-fed

controls. Ash weight and calcium content did not differ be-tween

the 2 groups, suggesting that decreased mechanical

strength could be due to decreased lysyl oxidase activity lead-ing

to lower crosslinking of the collagen. Rucker et al. (30)

made similar observations with bones from copper-deficient

chicks. Opsahl et al. (31) reported that lysyl oxidase was

impaired in copper-deficient chicks, which resulted in de-creased

torsion strength when levels of dietary copper dropped

below 1 mg/kg diet. Injection of the lathrogen,

beta-aminopro-prionitrile

(BAPN), an inhibitor of lysyl oxidase, resulted in

decreased hydroxypyridinnium crosslinks and decreased me-chanical

strength of femoral diaphyses (32). Others reported

that BAPN administration to rats can impair ligaments of

teeth (33,34). Iron is a cofactor for prolyl and lysyl hydroxy-lases,

enzymes that catalyze an ascorbate-dependent hydroxyl-ation

of prolyl and lysyl residues, essential steps prior to

crosslinking by lysyl oxidase (10). Using a scorbutic rat model,

Ellender and Gazelakis (35) reported reduced physical strength

of the caudal vertebrae. There is no consensus on the impor-tance

of crosslinks to bone strength. One school of thought

suggests that crosslinks increase toughness but do not have a

profound impact upon the stiffness or strength of bone (36).

Osteoporotic women have fewer crosslinks in bone collagen,

as reviewed by Burr and (23).

...

again posted on this fourth abstract before I was ready

to send this post. It may be a price of being slow. Oh well,

what might we learn from the full-text that is pdf-available?

As indicated below, first, the level of CR was 60%.

The venn diagram, which has mentioned the name of

in another post and it confused me, was demonstrated nicely

showing the overlap in three circles and the size of overlap

shared commensurate with the given number of genes that

overlap.

The discussion of male- and female-specific gene expressions

also seemed to be of interest.

I did not understand why there was no presentation of details

regarding the glucose levels in the mice. Looking at markers

of glucose seems to me to be too indirect a method, is it not?

J Nutr. 2004 Nov;134(11):2965-74.

Hepatic Genes Altered in Expression by Food Restriction Are Not

Influenced by

the Low Plasma Glucose Level in Young Male GLUT4 Transgenic Mice.

Fu C, Xi L, Wu Y, Mc R, A, Hickey M, Han ES.

Because food restriction (FR) has a profound effect on most tissues,

it is

plausible that the modulation of aging by FR occurs through cellular

processes

such as gene expression. The effect of FR in lowering plasma glucose

levels has

been demonstrated in mice, rats, and nonhuman primates. The

consistency of this

finding suggests that decreased plasma glucose may be an important

consequence

of FR. Indeed, lowering plasma glucose in the absence of FR would be

expected to

change the expression of some of the same genes as seen with FR.

GLUT4

transgenic (TG) mice were particularly suited to this examination

because they

have low plasma glucose levels like FR mice. We investigated altered

gene

expression by FR and the effect of low plasma glucose levels caused

by genetic

manipulation by measuring mRNA expression in liver tissues of 4- to

6-mo-old

mice with 2.5-4.5 mo of FR using microarrays and 4 groups: GLUT4 TG

(C57BL/6

background) consumed food ad libitum (AL), GLUT4 TG FR, wild-type

littermates

AL, and wild-type littermates FR. The 3 statistical analysis methods

commonly

indicated that FR altered the expression of 1277 genes; however, none

of these

genes was altered by additional GLUT4 expression. In fact, the low

plasma

glucose level in GLUT4 TG mice did not affect gene expression. Some

results were

confirmed by real-time quantitative RT-PCR. We conclude that a low

plasma

glucose level does not contribute to or coincide with the effect of

FR on gene

expression in the liver.

PMID: 15514260 [PubMed - in process]

... Abbreviations used: AL, consumed food ad libitum; cyp,

cytochrome P450;

cyp2B9, cytochrome P450, family 2, subfamily b, polypeptide 9;

cyp2B13, cyto-chrome

P450, family 2, subfamily b, polypeptide 13; cyp7B1, cytochrome P450,

family 7, subfamily b, polypeptide 1; dChip, DNA-chip analyzer; FDR,

false

discovery rate; FMO3, flavin-containing monooxygenase 3; FR, food

restriction;

GO, gene ontology; HSD3b5, 3beta-hydroxysteroid dehydrogenase V; MAS,

mi-croarray

suite; NTG, nontransgenic; PM, perfect match; QRT-PCR, quantitative

RT-PCR; SAM, significance analysis of microarrays; SAS, statistical

analysis

system; TG, transgenic.

... All

mice consumed ad libitum Harlan Teklad LM-485 mouse/rat steril-izable

diet No. 7912 5 until 6 wk of age. At 6 wk, half of the mice from

each group (18 from NTG group and 18 from TG group) were

allowed to continue to eat this diet (groups NTG AL and TG AL)

until killed. The remaining 36 mice (18 from NTG group and 18 from

TG group) were restricted to 60% of the mean food intake of group

AL until killed (groups NTG FR and TG FR). FR mice were given

their food allotment 1 h before the start of the dark phase of the

light

cycle.

... The distribution of the numbers of genes selected by all 3

methods of analysis among the 3 comparisons is illustrated

(Fig. 1). There were 1277, 333, and 207 genes in common to

the 3 analysis methods in the comparisons of AL vs. R, NTG

AL vs. TG FR, and TG AL vs. G FR, respectively. Only 115

genes robustly showed differential expression throughout all 3

of the comparisons. Among these 115 genes, 62 were upregu-lated

and 53 were downregulated by FR. Twenty each of the

most significantly up- and downregulated genes of the 115

genes with detectable expression levels (present call as calcu-lated

in MAS 5.0) in one or both treatment groups are shown

(Table 2). Flavin-containing monooxygenase 3 (FMO3) was

most upregulated by FR. Several genes from the cytochrome

P450 (cyp) family 2 as well as regulator of G-protein signaling

16 were upregulated by FR. In the case of G-protein signaling

16, two different probe sets, each with a different GenBank

accession number (U94828 or AV349152), indicated upregu-lation

of the gene by FR. Two genes from the glutathione

S-transferase family were among the genes upregulated by FR.

The gene most downregulated by FR was 3beta-hydroxysteroid

dehydrogenase V (HSD3b5). Several genes from the cyp fam-ily

(family 7, 4, and 2) were also among the genes downregu-lated

by FR. There are 2 probe sets, each with a different

GenBank accession number (U36993, AV141027), for the

cyp, family 7, subfamily b, polypeptide 1 (cyp7B1) gene. Both

probe sets were detected as significantly downregulated by FR.

... Real-time QRT-PCR results indicated 3

genes [FMO3; cyp, family 2, subfamily b, polypeptide 9

(cyp2B9); and cyp, family 2, subfamily b, polypeptide 13

(cyp2B13)] that have female specific expression in the liver

(22,23) were expressed (turned on) in the liver tissues of our

male FR mice and not expressed in the liver tissues of the male

AL mice. One gene (HSD3b5) that is male specific in liver

tissues (24) was not expressed (turned off) in FR samples (i.e.,

expressed in AL samples).

... FMO3 expression was shown

to be female specific in the mouse liver and this sex depen-dence

appears to be due to repression of FMO3 expression by

testosterone (26). Plasma testosterone is decreased by FR (27).

Therefore, the reduced levels of testosterone may no longer

repress FMO3 expression in male FR mice. The other 2 genes,

cyp2B9 and cyp2B13, which were turned on by FR, are also

female specific in the mouse liver (23). Since cyp2B9 is in-volved

in testosterone metabolism (28), its induction may be

partly responsible for the decreased testosterone in FR mice.

We also found 1 gene that was turned off by FR. HSD3b5

belongs to the 3beta-hydroxysteroid dehydrogenase family (24).

HDS3b5 is a NADPH-dependent 3-ketosteroid reductase and

does not biosynthesize active steroid hormones, but rather

converts an active androgen, dihydrotestosterone, into an

inactive androgen, 5 -androgen-3 ,17 -diol. The expression

of HSD3b5 is specific in the male mouse liver, and Wong and

Gill (28) reported that FR significantly suppressed HSD3b5

expression. Consistent with these findings, we observed that

FR turned off the expression of HSD3b5 in the male mouse

liver. Glucocorticoid downregulates HSD3b5 expression (28),

and our early study indicated that FR is associated with an

enhanced diurnal elevation of glucocorticoid (29). Thus, the

increased plasma glucocorticoid by FR may suppress HSD3b5

expression in the male FR mouse liver.

...

Cheers, Alan Pater