Modulatory Role for Substance P: DISCUSSION(3)


In addition to its ability to increase basal LH secretion, we have found that SP potentiates the stimulatory action of GnRH on LH release from porcine pituitary cells in static culture during a 4-h coincubation. In rats, analysis of the effects of SP on GnRH-induced LH release has led to contradictory results. Thus, whereas some authors have reported that SP at low concentrations potentiates, and at high doses inhibits, the GnRH stimulatory effect, others have found no effect or an inhibitory effect of SP in this regard. asthma inhalers

The mechanism(s) by which SP potentiates GnRH-induced LH release in our experimental model is presently unknown. However, other neuropeptides, such as pituitary adenylate cyclase-activating polypeptide (PACAP) and neuropeptide Y (NPY) have been shown to enhance GnRH-induced LH secretion in static cultures of rat pituitary cells, and the mechanisms mediating their effects have been investigated. In the case of PACAP, it has been suggested that the synergistic interaction with GnRH is likely to occur at different levels along the intracellular signaling cascades activated by both peptides (reviewed in ). More specifically, the ability of PACAP to activate the cAMP-protein kinase A system would potentiate, through a “cross-talk,” the stimulatory effects of GnRH on the phospholipase С (PLC)/inositol phosphate pathway leading to LH release. Although the mechanisms of action of SP on gonadotrophs have not been fully elucidated, there is compelling evidence that the intracellular signals activated by this neuropeptide are very similar to those activated by GnRH in this cell type.


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