AGENTS THAT INCREASE PHOSPHATIDIC-ACID INHIBIT THE LH-INDUCED TESTOSTERONE PRODUCTION

The results of the present study point to phosphatidic acid (PtdOH) as a possible intracellular messenger, which might be involved in local modulation of testicular testosterone production in vivo. Propranolol (27-266 mu M) induced an increased level of [H-3]PtdOH in isolated rat Leydig cells, prelabeled with [H-3]myristate, and at the same time a strong dose-dependent inhibition of the acute testosterone production stimulated by luteinizing hormone (LH). The inhibition was not bypasse d by the addition of dibutyryl-cAMP but was overcome, when 22(R)-hydro xycholesterol was added as a direct substrate for cytochrome P-450 sid e chain cleavage enzyme. Thus, the inhibition appears to be exerted at a point distal to cAMP-generation but before the first enzyme in the testosterone synthetic pathway. Treatment with other agents (4 beta-ph orbol 12-myristate 13-acetate (PMA), A23187, and sphingosine) giving r ise to increases in the PtdOH-level resulted in the inhibition of the LH-induced testosterone formation as well, thus indicating a connectio n between the two effects. Furthermore, we were able to demonstrate a highly significant correlation between the PtdOH-increase and the inhi bition of the LH-stimulated testosterone production. This may suggest a causal relationship between these two parameters.