Sex Hormone-Dependent Physiology and Diseases of Liver
Abstract
:1. Sex Hormone-Dependent Glucose Metabolism in a Healthy Liver, in Insulin Resistance (IR) and in Diabetes (T2D)
1.1. Cellular Transporters Involved in Glucose Transport: Their Expression in IR, T2D and MetS (metabolic syndrome)
1.2. Relationship between Androgens/Androgen Receptor/5α-Reductase and Hepatic Glucose Homeostasis
1.3. Relationship between Estrogens/Estrogen Receptors/Aromatase and Hepatic Glucose Homeostasis
2. Sex Hormone-Dependent Lipid Metabolism in the Normal Liver, in Nonalcoholic Fatty Liver Disease (NAFLD), Obesity and in Metabolic Syndrome (MetS)
2.1. Relationship between Estrogens/Estrogen Receptors/Aromatase and Hepatic Lipid Homeostasis
2.2. Correlation of Non-Alcoholic Fatty Liver Disease (NAFLD)/Non-Alcoholic Steatohepatitis (NASH) with Sex Steroids
3. HBV/HCV and Hepatocellular Carcinoma (HCC, Hepatoma)
3.1. Relationship between Estrogens/ERs and HBV-Related Acute Liver Failure Such as HCC
3.2. Relationship between Androgens/AR and HBV-Related Acute Liver Failure Such as HCC
3.3. Complicity of Noncoding mRNAs in the Onset and Progression of HCC
3.4. HCC Malignancy and Sex Hormones
3.5. Hypothesis about the Role of ERs in HCC
3.6. Immune Response in Liver Failure and Sex Hormones
3.7. Activity of Aromatase/Estrogens/ERs (and Variants) in HCC
4. Other Pathological Conditions and HCC
5. Pathological Condition Associated with the Biliary Tree
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ACACA | acetyl-CoA carboxylase alpha |
ACC | acetyl-CoA carboxylase |
AFP | alpha-fetoprotein |
ALIOS | American lifestyle-induced obesity syndrome |
ALP | alkaline phosphatase |
ALT | alanine aminotransferase |
AMPK | AMP-activated protein kinase |
AOX | fatty acyl-CoA oxidase |
AR | androgen receptor |
AR−/y | AR knockout male mice |
ARE | androgen response element |
AREG | amphiregulin |
ARKO | AR konockout |
ArKO | aromatase-knockout |
AST | aspartate aminotransferase |
ATP5J | ATPase coupling factor 6 |
BDL | bile duct ligation |
CCA | cholangiocarcinoma |
CCRKs | cell cycle-related kinases |
CLD | chronic liver disease |
CTCs | circulating tumor cells |
CTGF | connective tissue growth factor |
DEN | diethylnitrosamine |
DGAT1/2 | diacylglycerol O-acyltransferase 1/2 |
DHT | dihydrotestosterone |
DPN | bis-hydroxy-phenyl-propionitryle |
E2 | estradiol |
EGF-R | epidermal growth factor receptor |
ER | estrogen receptor |
ERα/ERβ | estrogen receptor alpha/estrogen receptor beta |
ERαKO/ERβKO | ERα knockout/ERβ knockout |
ESRRG | estrogen-related receptor gamma |
FA | fatty acid |
FASN | fatty acid synthase |
Foxa | forkhead box protein A |
GGT | γ-glutamyltransferase |
GLUT | glucose transporter |
GLR | glucagon receptor |
GPER | G protein-coupled estrogen receptor, known as Gpr30 |
Gpr30 | orphan G protein-coupled receptor 30 |
H-AR−/y | hepatic AR knockout male mice |
H-AR−/− | hepatic AR knockout female mice |
HBsAg | HBV surface antigen |
HBV | hepatitis B |
HBx | HBV X protein |
HCC | hepatocellular carcinoma |
HCV | hepatitis C |
HDL-C | high-density lipoprotein |
HepG2 | human liver cell line |
HFD | high-fat diet |
HFHC | high-fat and high-cholesterol diet |
HRT | hormone replacement therapy |
IBDM | intrahepatic bile duct mass |
IFN-γ | interferon γ |
IL-1β | interleukin 1β |
IL-6 | interleukin 6 |
IL-12A | interleukin 12A |
JNK | c-Jun N-terminal kinase |
KCNN4 | Ca2+-activated K+ channel |
L-AR−/y | liver AR knockout male mice |
LDL-C | low-density lipoprotein |
LKO | liver ERα-knockout |
lncRNA | long non-coding RNAs |
LT | lymphotoxin |
MetS | metabolic syndrome |
miR | microRNA |
MMP9 | matrix metalloproteinase 9 |
MOER | ERα at the plasma membrane |
MTA1 | metastasis-associated protein 1 |
MyD88 | myeloid differentiation primary response 88 |
NAFLD | non-alcoholic fatty liver disease |
NASH | non-alcoholic steatohepatitis |
NF-Κb | nuclear factor kappa B |
NK | natural killer |
ORX | orchidectomized |
OVX | ovariectomized |
PBC | primary biliary cirrhosis |
PCLD | polycystic liver disease |
PCOS | polycystic ovary syndrome |
PEPCK | phosphoenolpyruvate carboxykinase |
PI3K | phosphoinositide 3-kinase |
PPAR-α | proliferator-activated receptor-alpha |
PPAR-δ | peroxisome proliferation activator receptor-delta |
PPAR-γ | peroxisome proliferator activator receptor-gamma |
PPT | propyl-pyrazole-triol or trisphenol |
PR | progesterone receptor |
PSC | primary sclerosing cholangitis |
PTP1B | protein-tyrosine phosphatase 1B |
SCD1 | stearoyl-CoA desaturase-1 |
SGLT | Na+-coupled glucose transporters |
siRNA | small interfering RNA |
SREBP-1c | sterol-regulatory element-binding protein 1c |
STAT3 | signal transducer and activator of transcription 3 |
T | testosterone |
T2D | type 2 diabetes |
TCF | T cell factor |
Tfm | testicular feminized male mice |
TG | triglycerides |
TGF-β1 | transforming growth factor beta 1 |
TNFα | tumor necrosis factor alpha |
vER | variant estrogen receptor |
VLACS | very long fatty acyl-CoA synthetase |
WT | wild type |
wtER | wild type estrogen receptor |
XIAP | X-linked inhibitor of apoptosis protein |
5αR | 5α-reductase |
5αR1/5αR2 | 5α-reductase type1/5α-reductase type 2 |
5αR1−/−/5αR2−/− | 5α-reductase type1/5α-reductase type 2 knockout |
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Hormone Imbalance or Receptor/Enzyme Dysfunction | Results | References |
---|---|---|
Disturbed carbohydrate metabolism in male | ||
↓ Testosterone | Hyperglycemia, T2D, MetS | Muthusamy et al. [5] |
AR (lack) | IR, T2D | Lin et al. [4] |
AR knockout | ↓ Glucose metabolism, IR, hyperinsulinemia | Lin et al. [4] |
AR knockout + HFD | ↓ Sensitivity to insulin | Lin et al. [11] |
5α-red1 knockout + ALIOS | Hyperinsulinemia | Dowman et al. [12] |
5α-red1 knockout + HFD | Hyperinsulinemia | Livingstone et al. [13] |
↓ ERα | ↓ Glucose metabolism, IR, hyperinsulinemia, T2D, MetS | Zirilli et al. [16], Yamada et al. [28] |
ERαKO | ↓ Glucose tolerance, hepatic IR | Bryzgalova et al. [20], Nilsson et al. [29] |
↓ Testosterone | Hyperglycemia, T2D, MetS | Muthusamy et al. [5] |
Disturbed carbohydrate metabolism in female | ||
↓ Testosterone | ↑ Glucose | Kelly et al. [7] |
↓ Estrogens | ↑ Diabetes | Saengsirisuwan et al. [21], Feigh et al. [22] |
Hormone Imbalance or Receptor/Enzyme Dysfunction | Results | References |
---|---|---|
disturbed lipids metabolism in male | ||
↓ Testosterone | ↑ Hepatic steatosis ↓ Hepatic steatosis | Vőlzke et al. [64] Jones et al. [65] Schwingel et al. [66] |
5α-red1 knockout + ALIOS | Hepatic steatosis | Dowman et al. [12] |
5α-red1 knockout + HFD | ↑ TG, hepatic steatosis | Livingstone et al. [13] |
Hepatic AR- knockout + HFD | Hepatic steatosis, IR | Lin et al. [4], Lin et al. [11] |
↓ AR | ↑ TG in liver, hepatic steatosis | Lin et al. [4] |
ARKO | ↑ TG in liver, obesity, IR | Lin et al. [4] |
ArKO | Liver steatosis, obesity | Hewitt et al. [40], Fisher et al. [44] |
↓ Aromatase | Metabolic anomalies | Maffei et al. [15] |
↓ ERα + HFD | ↑ TG, ↑ diacylglyceride, IR | Zhu et al. [38] |
ERαKO | Fatty liver | Bryzgalova et al. [20] |
LKO + ↓ Gpr30 + HFD | ↑ TG, ↑ diacylglyceride | Zhu et al. [38], Meoli et al. [39] |
disturbed lipids metabolism in female | ||
↓ Estrogen | ↑ LDL-C, ↓ HDL-C, hepatic steatosis | Trapani et al. [71], Chen et al. [1] |
↓ Estrogen + HFD/HFHC | NASH | Kamada et al. [47] |
LKO + ↓ Gpr30 + HFD | ↑ TG, ↑ diacylglyceride, ↓ HDL-C, ↑ fat liver accumulation, IR | Zhu et al. [38], Meoli et al. [39] |
ERαKO | Fatty liver | Bryzgalova et al. [34] |
ArKO | Liver steatosis, obesity | Fisher et al. [44] |
Hyperandrogenism + PCOS | Obesity, IR, NAFLD | Bohdanowicz-Pawlak et al. [70] |
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Kur, P.; Kolasa-Wołosiuk, A.; Misiakiewicz-Has, K.; Wiszniewska, B. Sex Hormone-Dependent Physiology and Diseases of Liver. Int. J. Environ. Res. Public Health 2020, 17, 2620. https://doi.org/10.3390/ijerph17082620
Kur P, Kolasa-Wołosiuk A, Misiakiewicz-Has K, Wiszniewska B. Sex Hormone-Dependent Physiology and Diseases of Liver. International Journal of Environmental Research and Public Health. 2020; 17(8):2620. https://doi.org/10.3390/ijerph17082620
Chicago/Turabian StyleKur, Paulina, Agnieszka Kolasa-Wołosiuk, Kamila Misiakiewicz-Has, and Barbara Wiszniewska. 2020. "Sex Hormone-Dependent Physiology and Diseases of Liver" International Journal of Environmental Research and Public Health 17, no. 8: 2620. https://doi.org/10.3390/ijerph17082620