Sex hormone-related functions in regenerating male rat liver

Abstract

Sex hormone receptors were quantitated in normal male rat liver and in regenerating liver at several different times after partial (70%) hepatectomy. Both estrogen and androgen receptor content were altered dramatically by partial hepatectomy. Total hepatic content and nuclear retention of estrogen receptors increased, with the zenith evident 2 days after partial hepatectomy, corresponding to the zenith of mitotic index. Serum estradiol increased after 1 day, and reached a maximum at 3 days after surgery. In contrast, total and nuclear androgen receptor content demonstrated a massive decline at 1, 2, and 3 days after resection. Serum testosterone displayed a parallel decline. In addition, hepatic content of two androgen-responsive proteins was reduced to 15% and 13% of normal values during this period. The activity of these various proteins during regeneration of male rat liver is comparable to that observed in the liver of normal female rats. Taken together, these results indicate that partial hepatectomy induces a feminization of certain sexually dimorphic aspects of liver function in male rats. Furthermore, these data provide evidence that estrogens, but not androgens, may have an important role in the process of liver regeneration.

Figure 1

Variations in hepatic estrogen receptor activity after partial hepatectomy of male rats. Specific [³H]E₂ binding was measured in cytosolic and nuclear fractions prepared from livers of partially hepatectomized rats (days after 70% hepatectomy). The values are expressed as picomoles per gram liver for total liver content (A), cytosolic binding (B), and nuclear binding (C). B and C represent recalculations of data previously described in Reference . Serum E₂ levels (picograms per milliliter) as measured by specific radioimmunoassay are shown in D. The values are expressed as mean ± SD. Values differing from those at time 0 are indicated: *p < 0.005, **p < 0.01. Sham-operated animals killed at 24 and 48 h displayed receptor and serum E₂ levels identical to those animals killed at time 0.

Figure 2

Variations in hepatic androgen receptor activity after partial hepatectomy of male rats. Specific [³H]R1881 binding was measured in cytosolic and nuclear fractions prepared from livers of sham-operated (time 0) and partially hepatectomized rats (days after partial hepatectomy). The values are expressed as femtonic as per gram liver for total liver content (A), cytosolic binding (B), and nuclear binding (C). Serum testosterone levels are shown in D. The values expressed as mean ± SD and values differing from those at time 0 are indicated: *p < 0.005.

Figure 3

Activity of two hepatic androgen-responsive proteins after partial hepatectomy. Microsomal E2-OHase (A) activity was measured as the amount of [³H]2-methoxy-1,3,5(10)-estrien-17-one-3-ol product formed, and cytosolic MEB (B) was quantitated by its [³H]E₂ binding activity, as described in Materials and Methods. All groups consisted of at least 3 animals except for the MEB determination on day 2, which consisted of a single rat. The values are expressed as mean + SEM, and values differing from those observed at time 0 are indicated by *p < 0.005. Sham-operated animals were also tested at 24 and 48 h after surgery; the values for MEB and E2-OHase from these animals were identical to those of the time 0 control group.