Modulatory Role for Substance P: DISCUSSION(5)

DISCUSSION(5)

The dynamics of the effects of SP and/or GnRH on LH release were investigated by using a superfusion system in which pulsatile GnRH administration resembles the in vivo situation more closely than in static cultures of pituitary cells. Under these conditions, three successive pulses of GnRH or SP clearly stimulated LH release by anterior pituitary fragments, although a slight, but significant, decrease of the magnitude of the response was observed after the first pulse.

This decrease could suggest a loss of responsiveness or ‘desensitization’ of porcine gonadotrophs to the secretagogues, which may be related to the duration of both pulse and interpulse period. In contrast to observations in monolayer cultures, concurrent treatment with SP and GnRH in superfusion did not result in a synergistic stimulation of LH release, since peak LH amplitude and AUC elicited by GnRH alone, and by GnRH+SP, were similar. These findings are consistent with previous perifusion studies carried out with rat pituitary glands and suggest that a prolonged exposure to SP is likely to be required for this neuropeptide to enhance the stimulatory effect of GnRH on LH release. It is not known whether hypothalamic SP is secreted into the portal circulation and reaches the pituitary intermittently (as GnRH does) or continuously. buy asthma inhaler
On the other hand, the presence of SP within the pituitary is well established and supports a paracrine mode of action for this peptide. In this latter scenario, a more continuous exposure of gonadotrophs to SP would be feasible. It is also conceivable that the doses and administration pattern of GnRH and SP used were not the optimal for detecting a potentiation between the effects of both peptides in this experimental system. Notwithstanding, differences between the two culture systems employed could also contribute to the differential response to the combined treatment with SP and GnRH.

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