Regulation of the Truncation of Luteinizing Hormone Receptors at the Plasma Membrane Is Different in Rat and Mouse Leydig Cells*

Abstract

Regulation of the truncation of LH receptors was investigated in two types of mouse tumor Leydig cells (MA10 and MLTC-1), rat testis Leydig cells (RTL), and a rat tumor Leydig cell (R2C). Receptor numbers were measured by binding [125I]hCG to the cells cultured in monolayers. Addition of 3.3 nM LH for 2 h at 34 C had no detectable effect on binding sites in RTL or R2C cells, but in MA10 and MLTC-1 cells it caused a loss in binding sites. The effect on MA10 and MLTC-1 cells could be mimicked by inhibiting receptor internalization with 5 mM NaN3 and prevented by the addition of protease inhibitors. Incubating RTL and R2C cells with protease inhibitors caused a 2- to 3-fold increase in binding sites and a 2- to 3-fold increase in LH (0.033 and 0.33 nM)-stimulated cAMP production. When RTL and MA10 cells were incubated in the presence of [125I]hCG, a radioactive protein complex with an approximate mol wt of 80,000-90,000 was released into the incubation medium. We conclude that LH receptors are regulated by proteolysis at the plasma membrane in both mouse and rat Leydig cells. Furthermore, truncation of the LH receptor in the mouse Leydig cells is involved in down-regulation, whereas in the rat it is a continuous process.