[Cyclic AMP: role in the synthesis and release of luteinizing hormone]

GnRH is capable of inducing an increase in cyclic AMP (AMPc) production in the anterior pituitary gland. However, this intracellular messenger is not involved in the mechanisms leading to acute release of gonadotropins. Using anterior pituitary cells in culture, we recently found that AMPc, like GnRH, stimulated the expression of genes encoding for LH and consequently increased the synthesis of LH subunits. To reevaluate the role of AMPc in the secretion of pituitary gonadotropins, we first studied the effects of 8-Br-AMPc, a permeant AMPc analog, on LH release during a 48-hour period. Direct activation of protein kinases A by 8-Br-AMPc substantially stimulated LH release, to values as high as those seen with GnRH under the optimal conditions used in this experiment. However, kinetics were different, with GnRH inducing a rapid rise in LH and 8-Br-AMPc causing a gradual increase after a five-hour lag. We also studied the effects of 8-Br-AMPc on the release of neosynthesized subunits. Pituitary cells were incubated with 35S-Met, and labeled alpha and LH beta polypeptides were recovered in parallel from the cells and medium. We observed that 8-Br-AMPc stimulated not only LH synthesis but also release of newly synthesized LH subunits, in this respect 8-Br-AMPc was more effective than GnRH. After five hours incubation with 1.5 mM 8-Br-AMPc, 95% of the alpha subunit and 40% of the LH beta subunit that had been newly synthesized were released into the medium, whereas the corresponding figures with exposure to 10 nM GnRH were 80% and 15% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)