The Postnatal Offspring of Finasteride-Treated Male Rats Shows Hyperglycaemia, Elevated Hepatic Glycogen Storage and Altered GLUT2, IR, and AR Expression in the Liver
Background: A growing body of data indicates that the physiology of the liver is sex-hormone dependent, with some types of liver failure occurring more frequently in males, and some in females. In males, in physiological conditions, testosterone acts via androgen receptors (AR) to increase insulin r...
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/3/1242 |
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| author | Paulina Kur Agnieszka Kolasa-Wołosiuk Marta Grabowska Andrzej Kram Maciej Tarnowski Irena Baranowska-Bosiacka Sylwia Rzeszotek Małgorzata Piasecka Barbara Wiszniewska |
| author_facet | Paulina Kur Agnieszka Kolasa-Wołosiuk Marta Grabowska Andrzej Kram Maciej Tarnowski Irena Baranowska-Bosiacka Sylwia Rzeszotek Małgorzata Piasecka Barbara Wiszniewska |
| author_sort | Paulina Kur |
| collection | DOAJ |
| description | Background: A growing body of data indicates that the physiology of the liver is sex-hormone dependent, with some types of liver failure occurring more frequently in males, and some in females. In males, in physiological conditions, testosterone acts via androgen receptors (AR) to increase insulin receptor (IR) expression and glycogen synthesis, and to decrease glucose uptake controlled by liver-specific glucose transporter 2 (GLUT-2). Our previous study indicated that this mechanism may be impaired by finasteride, a popular drug used in urology and dermatology, inhibiting 5α-reductase 2, which converts testosterone (T) into dihydrotestosterone (DHT). Our research has also shown that the offspring of rats exposed to finasteride have an altered T–DHT ratio and show changes in their testes and epididymides. Therefore, the goal of this study was to assess whether the administration of finasteride had an trans-generational effect on (i) GLUT-2 dependent accumulation of glycogen in the liver, (ii) IR and AR expression in the hepatocytes of male rat offspring, (iii) a relation between serum T and DHT levels and the expression of GLUT2, IR, and AR mRNAs, (iv) a serum glucose level and it correlation with GLUT-2 mRNA. Methods: The study was conducted on the liver (an androgen-dependent organ) from 7, 14, 21, 28, and 90-day old Wistar male rats (F1:Fin) born by females fertilized by finasteride-treated rats. The control group was the offspring (F1:Control) of untreated Wistar parents. In the histological sections of liver the Periodic Acid Schiff (PAS) staining (to visualize glycogen) and IHC (to detect GLUT-2, IR, and AR) were performed. The liver homogenates were used in qRT-PCR to assess GLUT2, IR, and AR mRNA expression. The percentage of PAS-positive glycogen areas were correlated with the immunoexpression of GLUT-2, serum levels of T and DHT were correlated with GLUT-2, IR, and AR transcript levels, and serum glucose concentration was correlated with the age of animals and with the GLUT-2 mRNA by Spearman’s rank correlation coefficients. Results: In each age group of F1:Fin rats, the accumulation of glycogen was elevated but did not correlate with changes in GLUT-2 expression. The levels of GLUT-2, IR, and AR transcripts and their immunoreactivity statistically significantly decreased in F1:Fin animals. In F1:Fin rats the serum levels of T and DHT negatively correlated with androgen receptor mRNA. The animals from F1:Fin group have statistically elevated level of glucose. Additionally, in adult F1:Fin rats, steatosis was observed in the liver (see Appendix A). Conclusions: It seems that treating male adult rats with finasteride causes changes in the carbohydrate metabolism in the liver of their offspring. This can lead to improper hepatic energy homeostasis or even hyperglycaemia, insulin resistance, as well as some symptoms of metabolic syndrome and liver steatosis. |
| first_indexed | 2024-03-09T03:31:30Z |
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| last_indexed | 2024-03-09T03:31:30Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6fd14e9020b94d60a6eb3fe7ee64a6482023-12-03T14:55:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223124210.3390/ijms22031242The Postnatal Offspring of Finasteride-Treated Male Rats Shows Hyperglycaemia, Elevated Hepatic Glycogen Storage and Altered GLUT2, IR, and AR Expression in the LiverPaulina Kur0Agnieszka Kolasa-Wołosiuk1Marta Grabowska2Andrzej Kram3Maciej Tarnowski4Irena Baranowska-Bosiacka5Sylwia Rzeszotek6Małgorzata Piasecka7Barbara Wiszniewska8Department of Histology and Embryology, Pomeranian Medical University (PMU), Powstańców Wlkp. 72 Avene, 70-111 Szczecin, PolandDepartment of Histology and Embryology, Pomeranian Medical University (PMU), Powstańców Wlkp. 72 Avene, 70-111 Szczecin, PolandDepartment of Histology and Developmental Biology, Pomeranian Medical University, Żołnierska 48 Street, 71-210 Szczecin, PolandDepartment of Pathology, West Pomeranian Oncology Center, Strzałowska 22 Street, 71-730 Szczecin, PolandDepartment of Physiology, Pomeranian Medical University, Powstańców Wlkp. 72 Avenue, 70-111 Szczecin, PolandDepartment of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72 Avenue, 70-111 Szczecin, PolandDepartment of Histology and Embryology, Pomeranian Medical University (PMU), Powstańców Wlkp. 72 Avene, 70-111 Szczecin, PolandDepartment of Histology and Developmental Biology, Pomeranian Medical University, Żołnierska 48 Street, 71-210 Szczecin, PolandDepartment of Histology and Embryology, Pomeranian Medical University (PMU), Powstańców Wlkp. 72 Avene, 70-111 Szczecin, PolandBackground: A growing body of data indicates that the physiology of the liver is sex-hormone dependent, with some types of liver failure occurring more frequently in males, and some in females. In males, in physiological conditions, testosterone acts via androgen receptors (AR) to increase insulin receptor (IR) expression and glycogen synthesis, and to decrease glucose uptake controlled by liver-specific glucose transporter 2 (GLUT-2). Our previous study indicated that this mechanism may be impaired by finasteride, a popular drug used in urology and dermatology, inhibiting 5α-reductase 2, which converts testosterone (T) into dihydrotestosterone (DHT). Our research has also shown that the offspring of rats exposed to finasteride have an altered T–DHT ratio and show changes in their testes and epididymides. Therefore, the goal of this study was to assess whether the administration of finasteride had an trans-generational effect on (i) GLUT-2 dependent accumulation of glycogen in the liver, (ii) IR and AR expression in the hepatocytes of male rat offspring, (iii) a relation between serum T and DHT levels and the expression of GLUT2, IR, and AR mRNAs, (iv) a serum glucose level and it correlation with GLUT-2 mRNA. Methods: The study was conducted on the liver (an androgen-dependent organ) from 7, 14, 21, 28, and 90-day old Wistar male rats (F1:Fin) born by females fertilized by finasteride-treated rats. The control group was the offspring (F1:Control) of untreated Wistar parents. In the histological sections of liver the Periodic Acid Schiff (PAS) staining (to visualize glycogen) and IHC (to detect GLUT-2, IR, and AR) were performed. The liver homogenates were used in qRT-PCR to assess GLUT2, IR, and AR mRNA expression. The percentage of PAS-positive glycogen areas were correlated with the immunoexpression of GLUT-2, serum levels of T and DHT were correlated with GLUT-2, IR, and AR transcript levels, and serum glucose concentration was correlated with the age of animals and with the GLUT-2 mRNA by Spearman’s rank correlation coefficients. Results: In each age group of F1:Fin rats, the accumulation of glycogen was elevated but did not correlate with changes in GLUT-2 expression. The levels of GLUT-2, IR, and AR transcripts and their immunoreactivity statistically significantly decreased in F1:Fin animals. In F1:Fin rats the serum levels of T and DHT negatively correlated with androgen receptor mRNA. The animals from F1:Fin group have statistically elevated level of glucose. Additionally, in adult F1:Fin rats, steatosis was observed in the liver (see Appendix A). Conclusions: It seems that treating male adult rats with finasteride causes changes in the carbohydrate metabolism in the liver of their offspring. This can lead to improper hepatic energy homeostasis or even hyperglycaemia, insulin resistance, as well as some symptoms of metabolic syndrome and liver steatosis.https://www.mdpi.com/1422-0067/22/3/1242glycogen storageGLUT-2ARIRfinasterideDHT deficiency |
| spellingShingle | Paulina Kur Agnieszka Kolasa-Wołosiuk Marta Grabowska Andrzej Kram Maciej Tarnowski Irena Baranowska-Bosiacka Sylwia Rzeszotek Małgorzata Piasecka Barbara Wiszniewska The Postnatal Offspring of Finasteride-Treated Male Rats Shows Hyperglycaemia, Elevated Hepatic Glycogen Storage and Altered GLUT2, IR, and AR Expression in the Liver International Journal of Molecular Sciences glycogen storage GLUT-2 AR IR finasteride DHT deficiency |
| title | The Postnatal Offspring of Finasteride-Treated Male Rats Shows Hyperglycaemia, Elevated Hepatic Glycogen Storage and Altered GLUT2, IR, and AR Expression in the Liver |
| title_full | The Postnatal Offspring of Finasteride-Treated Male Rats Shows Hyperglycaemia, Elevated Hepatic Glycogen Storage and Altered GLUT2, IR, and AR Expression in the Liver |
| title_fullStr | The Postnatal Offspring of Finasteride-Treated Male Rats Shows Hyperglycaemia, Elevated Hepatic Glycogen Storage and Altered GLUT2, IR, and AR Expression in the Liver |
| title_full_unstemmed | The Postnatal Offspring of Finasteride-Treated Male Rats Shows Hyperglycaemia, Elevated Hepatic Glycogen Storage and Altered GLUT2, IR, and AR Expression in the Liver |
| title_short | The Postnatal Offspring of Finasteride-Treated Male Rats Shows Hyperglycaemia, Elevated Hepatic Glycogen Storage and Altered GLUT2, IR, and AR Expression in the Liver |
| title_sort | postnatal offspring of finasteride treated male rats shows hyperglycaemia elevated hepatic glycogen storage and altered glut2 ir and ar expression in the liver |
| topic | glycogen storage GLUT-2 AR IR finasteride DHT deficiency |
| url | https://www.mdpi.com/1422-0067/22/3/1242 |
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