Mechanism of luteinizing hormone regulation of prostaglandin synthesis in rat granulosa cells.

The present study was undertaken to examine the mechanism by which luteinizing hormone (LH) stimulates prostaglandin (PG) synthesis in rat granulosa cells. Immature rats were injected with 20 IU of pregnant mare's serum gonadotropin and granulosa cells isolated 48 h later. LH (5 microgram/ml) stimulated PGE synthesis markedly over the control with no additions in 6-h incubations (1.98 +/- 0.24 and 0.24 +/- 0.05 ng/2 X 10(6) cells, respectively, n = 6). When arachidonic acid (100 microgram/ml) was included during the last hour of incubation, further increases to 15.4 +/- 2.9 and 2.48 +/- 0.48 ng of PGE/2 X 10(6) cells in LH and control incubations were observed. The cause of the increased response to a 1-h incubation with arachidonic acid in the LH-treated cells did not appear to be a stimulation of fatty acid uptake. In addition, when cellular lipids were labeled by a 2-h incubation with radioactive arachidonic acid, LH did not stimulate intra- or extracellular release of arachidonic acid. A 5-fold stimulation of prostaglandin synthetase activity, however, was observed in cells incubated with LH for 5 h. Our results, therefore, indicate that LH acts at a step in the prostaglandin pathway after hydrolysis of arachidonic acid esters and produces an increase in prostaglandin synthetase activity.