Endocrine Abstracts (2009) 20 P620

Influence of hyperprolactinemia on prolactin receptor manifestation and hepatic bilirubin excretory activity under condition of female rat obstructive cholestasis

Natalia Kushnareva, Maria Sergeeva & Olga Smirnova

M V Lomonosov Moscow State University, Moscow, Russian Federation.

Ordinary complication of pregnancy is shift of hepatic excretory activity leading to cholestasis. Gallstone disease is also predominated in women. Both high prolactin (Prl) concentration and high level of liver prolactin receptors (PrlR) in normal and pregnant women were assumed to participate in obstructive cholestasis development.

Using female rat model of hyperprolactinemia combined with obstructive cholestasis we aimed to investigate Prl influence on female rat liver PrlR expression, alterations of hepatic structure and liver bilirubin excretory activity.

Obstructive cholestasis was induced by common bile duct ligation and hyperprolactinemia by female donor pituitary transplantation under kidney capsule of female recipient. Intensity of PrlR manifestation was analyzed with indirect immunohistochemical technique with quantitative computer analysis of imaging. Bilirubin concentration in bile, blood, and urine, bile flow and bilirubin excretion rates were tested.

Hyperprolactinemia induced elevation of PrlR manifestation in hepatocytes under normal and obstructive cholestasis conditions. PrlR expression in cholangiocytes was sharply increased in obstructive cholestasis with no additional influence of hyperprolactinemia and decreased after bile duct decompression.

Hyperprolactinemia in conjunction with elevated hepatocyte and cholangiocyte PrlR manifestation caused additional alterations in hepatic structure and functions as compared to obstructive cholestasis influence: 1) amount and size of bile ducts were additionally increased with occasionally observed ducts with elements of intestinal metaplasia; 2) fibrosis and inflammation of periportal areas were more prominent; 3) depending on hyperprolactinemia duration restoration of bile flow after bile duct decompression was firstly suppressed and then not restored; and 4) bilirubin concentration was firstly elevated in blood and urine and then decreased in bile.

Thus, hyperprolactinemia under obstructive cholestasis condition is accompanied by elevation of hepatocyte PrlR manifestation and may further damage liver structure, aggravate liver functions and participate in redirection of bile flux from liver to blood and urine.

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