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Partial hepatectomy induces delayed hepatocyte proliferation and normal liver regeneration in ovariectomized mice.

Umeda M, Hiramoto M, Imai T - Clin Exp Gastroenterol (2015)

Bottom Line: Both E2 administration and PH induced the gene expression of estrogen receptor α (ERα).The transcripts of ERα were detected specifically in periportal hepatocytes after E2 administration and PH.Moreover, the E2 concentrations and hepatocyte proliferation rates were highest in the proestrus period of the estrous cycle.

View Article: PubMed Central - PubMed

Affiliation: Department of Aging Intervention, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.

ABSTRACT
Estrogens play central roles in sexual development, reproduction, and hepatocyte proliferation. The ovaries are one of the main organs for estradiol (E2) production. Ovariectomies (OVXs) were performed on the female mice, and hepatocyte proliferation was analyzed. The ovariectomized mice exhibited delayed hepatocyte proliferation after partial hepatectomy (PH) and also exhibited delayed and reduced E2 induction. Both E2 administration and PH induced the gene expression of estrogen receptor α (ERα). The transcripts of ERα were detected specifically in periportal hepatocytes after E2 administration and PH. Moreover, the E2 concentrations and hepatocyte proliferation rates were highest in the proestrus period of the estrous cycle. Taken together, these findings indicate that E2 accelerated ERα expression in periportal hepatocytes and hepatocyte proliferation in the female mice.

No MeSH data available.


Related in: MedlinePlus

The estrous cycle regulated E2 concentration and hepatocyte proliferation.Notes: (A) Both of hepatocyte proliferation (left y-axis, BrdU-positive hepatocytes, and the open hexagons with dotted lines) and the circulating concentration of E2 (right y-axis and the filled triangle) were increased in an E2 dose of 0 (Veh), 1, 3, 10, 30, and 100 mg/30 g body weight. The values are expressed as the mean ± SEM (n=5). *P<0.05. (B) The estrous cycle regulated E2 concentration (right y-axis and the filled rectangles) and hepatocyte proliferation (left y-axis, BrdU-positive hepatocytes, and the open circle). The values are expressed as the mean ± SEM (n=5). *P<0.05. (C) Possible model of the estrous cycle regulated hepatocyte proliferation.Abbreviations: E2, estradiol; BrdU, bromodeoxyuridine; SEM, standard error of the mean.
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f2-ceg-8-175: The estrous cycle regulated E2 concentration and hepatocyte proliferation.Notes: (A) Both of hepatocyte proliferation (left y-axis, BrdU-positive hepatocytes, and the open hexagons with dotted lines) and the circulating concentration of E2 (right y-axis and the filled triangle) were increased in an E2 dose of 0 (Veh), 1, 3, 10, 30, and 100 mg/30 g body weight. The values are expressed as the mean ± SEM (n=5). *P<0.05. (B) The estrous cycle regulated E2 concentration (right y-axis and the filled rectangles) and hepatocyte proliferation (left y-axis, BrdU-positive hepatocytes, and the open circle). The values are expressed as the mean ± SEM (n=5). *P<0.05. (C) Possible model of the estrous cycle regulated hepatocyte proliferation.Abbreviations: E2, estradiol; BrdU, bromodeoxyuridine; SEM, standard error of the mean.

Mentions: PH induces E2 concentration9,11,12,20 (Figure 1) as well as hepatocyte proliferation (Figure 2).14,15 E2 was administered to the OVX mice, and hepatocyte proliferation was analyzed (Figure 2A). E2 administration induced hepatocyte proliferation in the OVX mice in a dose-dependent manner (Figure 2A and B).32 The target factors of E2 are ERα, ERβ, and GPR30,3–6 and the ICI182780 (ICI) is one of the selective ER modulators (SERMs). ICI is an antagonist for ERα and ERβ, but an agonist for GPR30.5,6,33,34 ICI reduced hepatocyte proliferation (Figure 3B), which indicates that the target(s) of E2 action is related to hepatocyte proliferation that was not GPR30 but could have been ERα and/or ERβ. Moreover, no ERβ expression was observed in the male livers.19,20


Partial hepatectomy induces delayed hepatocyte proliferation and normal liver regeneration in ovariectomized mice.

Umeda M, Hiramoto M, Imai T - Clin Exp Gastroenterol (2015)

The estrous cycle regulated E2 concentration and hepatocyte proliferation.Notes: (A) Both of hepatocyte proliferation (left y-axis, BrdU-positive hepatocytes, and the open hexagons with dotted lines) and the circulating concentration of E2 (right y-axis and the filled triangle) were increased in an E2 dose of 0 (Veh), 1, 3, 10, 30, and 100 mg/30 g body weight. The values are expressed as the mean ± SEM (n=5). *P<0.05. (B) The estrous cycle regulated E2 concentration (right y-axis and the filled rectangles) and hepatocyte proliferation (left y-axis, BrdU-positive hepatocytes, and the open circle). The values are expressed as the mean ± SEM (n=5). *P<0.05. (C) Possible model of the estrous cycle regulated hepatocyte proliferation.Abbreviations: E2, estradiol; BrdU, bromodeoxyuridine; SEM, standard error of the mean.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4494181&req=5

f2-ceg-8-175: The estrous cycle regulated E2 concentration and hepatocyte proliferation.Notes: (A) Both of hepatocyte proliferation (left y-axis, BrdU-positive hepatocytes, and the open hexagons with dotted lines) and the circulating concentration of E2 (right y-axis and the filled triangle) were increased in an E2 dose of 0 (Veh), 1, 3, 10, 30, and 100 mg/30 g body weight. The values are expressed as the mean ± SEM (n=5). *P<0.05. (B) The estrous cycle regulated E2 concentration (right y-axis and the filled rectangles) and hepatocyte proliferation (left y-axis, BrdU-positive hepatocytes, and the open circle). The values are expressed as the mean ± SEM (n=5). *P<0.05. (C) Possible model of the estrous cycle regulated hepatocyte proliferation.Abbreviations: E2, estradiol; BrdU, bromodeoxyuridine; SEM, standard error of the mean.
Mentions: PH induces E2 concentration9,11,12,20 (Figure 1) as well as hepatocyte proliferation (Figure 2).14,15 E2 was administered to the OVX mice, and hepatocyte proliferation was analyzed (Figure 2A). E2 administration induced hepatocyte proliferation in the OVX mice in a dose-dependent manner (Figure 2A and B).32 The target factors of E2 are ERα, ERβ, and GPR30,3–6 and the ICI182780 (ICI) is one of the selective ER modulators (SERMs). ICI is an antagonist for ERα and ERβ, but an agonist for GPR30.5,6,33,34 ICI reduced hepatocyte proliferation (Figure 3B), which indicates that the target(s) of E2 action is related to hepatocyte proliferation that was not GPR30 but could have been ERα and/or ERβ. Moreover, no ERβ expression was observed in the male livers.19,20

Bottom Line: Both E2 administration and PH induced the gene expression of estrogen receptor α (ERα).The transcripts of ERα were detected specifically in periportal hepatocytes after E2 administration and PH.Moreover, the E2 concentrations and hepatocyte proliferation rates were highest in the proestrus period of the estrous cycle.

View Article: PubMed Central - PubMed

Affiliation: Department of Aging Intervention, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan.

ABSTRACT
Estrogens play central roles in sexual development, reproduction, and hepatocyte proliferation. The ovaries are one of the main organs for estradiol (E2) production. Ovariectomies (OVXs) were performed on the female mice, and hepatocyte proliferation was analyzed. The ovariectomized mice exhibited delayed hepatocyte proliferation after partial hepatectomy (PH) and also exhibited delayed and reduced E2 induction. Both E2 administration and PH induced the gene expression of estrogen receptor α (ERα). The transcripts of ERα were detected specifically in periportal hepatocytes after E2 administration and PH. Moreover, the E2 concentrations and hepatocyte proliferation rates were highest in the proestrus period of the estrous cycle. Taken together, these findings indicate that E2 accelerated ERα expression in periportal hepatocytes and hepatocyte proliferation in the female mice.

No MeSH data available.


Related in: MedlinePlus