Modulatory Role for Substance P: DISCUSSION(1)

DISCUSSION(1) An emerging body of evidence derived from morphological, biochemical, and physiological studies suggests that SP can play a relevant role in the regulation of the hypothalamo-gonadotropic axis. However, there is a dearth of information on the effects that SP can exert on gonadotrophs from species other than the rat. Likewise, the possible interaction of SP with GnRH, the main factor controlling gonadotroph function, has hitherto received little attention. In the present study, we provide unequivocal evidence that SP stimulates LH release from cultures of porcine gonadotrophs and that this effect is not mediated via a GnRH receptor. Furthermore, we show that under certain conditions SP can enhance the stimulatory effect of GnRH on LH secretion.
Our initial set of studies with monolayer cultures of porcine pituitary cells clearly demonstrated the ability of SP to stimulate LH secretion in a dose-dependent manner. The SP effect was significant at concentrations at, or above, 100 nM. However, the secretory response induced by SP seemed to be of lower magnitude than that elicited by GnRH, since the typical LH increase induced by 10 nM GnRH was mimicked only by a 10-(xM dose of SP. Our results are consistent with those reported for pituitary cells from female rats by Shamgochian and Leeman in that only 100-nM doses or higher of SP elicited significant LH increases. Moreover, in the same study, differences in the magnitude of LH response to GnRH and SP were comparable to those found here for porcine gonadotrophs. Results from binding studies indicate that the density of SP receptors in rat pituitary cells is lower than that for other secre-tagogues. buy asthma inhalers
If a similar situation occurs in the porcine pituitary, it would account for the lower magnitude of response to SP with respect to GnRH observed herein. On the other hand, none of the doses of SP tested significantly modified the intracellular LH content in the cultures. Although the possible changes in LH mRNA levels in response to SP treatment have not yet been determined, this lack of effect of SP in pLH content probably reflects the maintenance of a balance between hormone release and the production of new hormone during the 4-h incubation. Therefore, our results demonstrate that SP acts on porcine gonadotrophs to stimulate LH release and to maintain the levels of immunoreactive pLH stored in static cultures of porcine pituitary cells.

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