Estrogen induction of very low density apolipoprotein II synthesis, a major avian liver yolk protein, involves the recruitment of hepatocytes.

The mechanism of steroid hormone action was studied in the cockerel liver. Very low density apolipoprotein II (apo-VLDL-II), a yolk protein, is a low molecular weight apolipoprotein that is inducible by estrogen. The intracellular apo-VLDL-II messenger RNA (mRNA) concentration under various hormonal conditions was examined by a dot-blot assay. The concentration was very low in untreated cockerels (approximately 0.5 molecule per cell). It increased to 8,000 molecules per cell within 24 h of estrogen treatment and reached a maximum level of approximately 70,000 molecules per cell after 14 daily doses of estrogen. The distribution of hepatocytes harboring apo-VLDL-II and its mRNA was studied by immunohistochemistry and by in situ nucleic acid hybridization to cloned [3H]apo-VLDL-II complementary DNA (cDNA). The number of cells containing the immunoreactive protein and the hybridizable mRNA increased from extremely low (0.3% and 0.27%, respectively) to substantial (11% and 10%, respectively) at 24 h after estrogen treatment and to extremely high (94% and 92%, respectively) in maximally treated animals. Our studies indicate that, in addition to enhanced transcription and stabilization of mRNA, the recruitment of liver cells previously not engaged in the synthesis of apo-VLDL-II is an important mechanism by which the hormone induces the hepatic production of this protein. The phenomenon of recruitment and the heterogeneity of the functional capacity of individual hepatocytes to respond to estrogen may be important to our understanding of estrogen action in the liver.