Octreotide inhibits liver regeneration by suppressing regional estrogen receptor type a expression.

Background and Rationale: Liver regeneration involves a significant variety of growth and paracrine factors. Octreotide has long been shown to inhibit liver regeneration, although the exact mechanism of its action remains unclear. This paper aims to examine the effect of long-term octreotide administration on the expression of the estrogen receptor type alpha (Era) as a potential novel pathway via which liver regeneration may be hindered. Sixty adult male Wistar rats were submitted to 70% (extensive) hepatectomy and subsequently randomized to receive either a subcutaneous injection of 50grams/kg body weight octreotide diluted in 1mL of 0.9% normal saline (SS group) or simply 1mL of 0.9% normal saline (NS group). Animals were followed up to 168 or 1440h (1 week and 1 month, respectively) post-hepatectomy and subsequently sacrificed. Removed livers were weighted, diluted in paraformaldehyde, embedded in paraffin wax, sliced at 5 micrometer intervals and prepared for the immunohistochemical detection of ERa. The control group labeling indices for both hepatocytes and cholangiocytes at 168 and 1440h were higher at a statistically significant degree compared to age-matched SS group animals. Interestingly, ERa expression is significantly increased over time in control animals for both cell types examined, while this is not true for animals receiving octreotide. In conclusion, octreotide-mediated inhibition of liver regeneration involves the long-term down-regulation of ERa expression in hepatocytes and cholangiocytes. This hormonal cross-talk may be of particular significance to explain sex-specific differences in liver repair dynamics.