Hepatic intracellular distribution of pregnenolone-16alpha-carbonitrile and its influence on adenyl cyclase activity in rat liver cells

Abstract

Pregnenolone-16alpha-carbonitrile (PCN) enhanced adenyl cyclase activity in the liver cells of female Sprague-Dawley rats. Injection of 14C-PCN and fractionation of hepatocytes into nuclei, mitochondria, total ribosomes, endoplasmic reticulum (ER) membranes, cytosol and plasma membranes revealed that after 4 h there was a preferential localization of the cyanosteroid in ER membranes. Total ribosomes and cytosolar proteins seemed to contain less PCN after 4 h, the optimal time for maximal penetration and intracellular establishment. On the other hand, PCN was localized preferentially in plasma membranes after 2 h and this diminished with time. Only trace amounts of the cyanosteroid were found in the nuclei and mitochondria, from the time of its intracellular introduction to the time of its apparent removal from the hepatocyte.