Sex hormones differently regulate lipid metabolism genes in primary human hepatocytes.

Autor: Seidemann L; Department of Hepatobiliary Surgery and Visceral Transplantation, Clinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, 04103, Leipzig, Germany.; Saxonian Incubator for Clinical Translation (SIKT), Leipzig University, 04103, Leipzig, Germany., Lippold CP; Department of Hepatobiliary Surgery and Visceral Transplantation, Clinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, 04103, Leipzig, Germany.; Saxonian Incubator for Clinical Translation (SIKT), Leipzig University, 04103, Leipzig, Germany., Rohm CM; Department of Hepatobiliary Surgery and Visceral Transplantation, Clinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, 04103, Leipzig, Germany.; Saxonian Incubator for Clinical Translation (SIKT), Leipzig University, 04103, Leipzig, Germany., Eckel JC; Department of Hepatobiliary Surgery and Visceral Transplantation, Clinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, 04103, Leipzig, Germany.; Saxonian Incubator for Clinical Translation (SIKT), Leipzig University, 04103, Leipzig, Germany., Schicht G; Department of Hepatobiliary Surgery and Visceral Transplantation, Clinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, 04103, Leipzig, Germany.; Saxonian Incubator for Clinical Translation (SIKT), Leipzig University, 04103, Leipzig, Germany., Matz-Soja M; Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103, Leipzig, Germany., Berg T; Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, 04103, Leipzig, Germany., Seehofer D; Department of Hepatobiliary Surgery and Visceral Transplantation, Clinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, 04103, Leipzig, Germany., Damm G; Department of Hepatobiliary Surgery and Visceral Transplantation, Clinic for Visceral, Transplant, Thoracic and Vascular Surgery, Leipzig University Medical Center, 04103, Leipzig, Germany. georg.damm@medizin.uni-leipzig.de.; Saxonian Incubator for Clinical Translation (SIKT), Leipzig University, 04103, Leipzig, Germany. georg.damm@medizin.uni-leipzig.de.
Jazyk: angličtina
Zdroj: BMC endocrine disorders [BMC Endocr Disord] 2024 Aug 01; Vol. 24 (1), pp. 135. Date of Electronic Publication: 2024 Aug 01.
DOI: 10.1186/s12902-024-01663-9
Abstrakt: Background: Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher in men than in women. Hormonal and genetic causes may account for the sex differences in MASLD. Current human in vitro liver models do not sufficiently take the influence of biological sex and sex hormones into consideration.
Methods: Primary human hepatocytes (PHHs) were isolated from liver specimen of female and male donors and cultured with sex hormones (17β-estradiol, testosterone and progesterone) for up to 72 h. mRNA expression levels of 8 hepatic lipid metabolism genes were analyzed by RT-qPCR. Sex hormones and their metabolites were determined in cell culture supernatants by LC-MS analyses.
Results: A sex-specific expression was observed for LDLR (low density lipoprotein receptor) with higher mRNA levels in male than female PHHs. All three sex hormones were metabolized by PHHs and the effects of hormones on gene expression levels varied depending on hepatocyte sex. Only in female PHHs, 17β-estradiol treatment affected expression levels of PPARA (peroxisome proliferator-activated receptor alpha), LIPC (hepatic lipase) and APOL2 (apolipoprotein L2). Further changes in mRNA levels of female PHHs were observed for ABCA1 (ATP-binding cassette, sub-family A, member 1) after testosterone and for ABCA1, APOA5 (apolipoprotein A-V) and PPARA after progesterone treatment. Only the male PHHs showed changing mRNA levels for LDLR after 17β-estradiol and for APOA5 after testosterone treatment.
Conclusions: Male and female PHHs showed differences in their expression levels of hepatic lipid metabolism genes and their responsiveness towards sex hormones. Thus, cellular sex should be considered, especially when investigating the pathophysiological mechanisms of MASLD.
(© 2024. The Author(s).)
Databáze: MEDLINE
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