p-Chlorophenylalanine-induced proliferation of the seminal vesicle epithelium

Intraperitoneal injection of p-chlorophenylalanine (pCPA) methylester (100 mg/kg body weight) results in an activation of the lysosomal system of the secretory cells in the rat seminal vesicle and an elevation of the activities of lysosomal enzymes within 15 min following the injection. Large autophagic vacuoles are formed, sequestering rough endoplasmic reticulum and part of the Golgi apparatus within 2 h. Shortly after the activation of the lysosomal system an elevation of both DNA- and protein synthesis is measured biochemically. 6 h subsequent to the injection a wave o mitoses of the secretory cells begins, reaching a maximum of 6 h later and then declining within 3 h. About 12 h following the injection a second rise in lysosomal activity begins, declining within 24 h. The entire sequence of lysosomal and proliferative activities is inhibited in antiandrogen-pretreated rats. Deduced from these findings the following hypothesis of growth regulation of the accessory sex glands is advanced: enhanced loss of intracellular material during autophagocytosis diminishes the intracellular concentration of a substance curtailing cell division below its effective threshold resulting in division of the secretory cells. The prerequisites of this mechanism are (i) a sufficient distributive capacity of the stroma for hormones (androgens) and metabolic precursors, and (ii) sufficient capacity of the basal cells for transporting the precursors to the secretory cells. Sloughing of the secretory cells separates them from these auxiliary structures (stroma and basal cells) and enables the basal cells to divide.