Studies of lysosomes—VI: The effect of neutral steroids and bile acids on lysosomes in vitro

Abstract

The effect of steroid hormones and bile acids on the release of hydrolases from lysosomes in granular fractions of rabbit liver and leukocytes has been studied in sucrose suspensions. At concentrations above 2.5 × 10 −4 M, steroids such as etiocholanolone, pregnanedione, pregnanolone, lithocholic acid, and progesterone were found to release β-glucuronidase and acid phosphatase activity from granules of rabbit liver. Metabolic precursors of etiocholanolone, such as testosterone, dehydroepiandrosterone, or 11-desoxycortisol, were active at 37° but not at 20°. Whereas these 5-β-H and Δ4,5 or Δ5,6 steroids released enzymes from the granules into the suspending medium, no 5-α-H isomer, such as androsterone, had comparable activity. Oxygenation or hydroxylation of carbon-11 of pregnanolone or etiocholanolone decreased the activity on the granules of the steroids. Pretreatment of liver granules with cortisol acetate, cortisone acetate, or chloroquine diminished the release of acid hydrolases by etiocholanolone or progesterone. Both etiocholanolone and progesterone reduced the apparent absorbance of suspensions of isolated leukocyte granules, and released β-glucuronidase from the particles, without physically disrupting the majority of granules. The data are compatible with the hypothesis that lysosomes are disrupted by pyrogenic steroids; the relationship of this action in vitro to their fever-provoking capacity in man has yet to be determined.