Neonatal hypothalamic XXXX expression in an excitotoxicity-induced model of precocious puberty.

@entity1024 @entity3390 @entity4 @entity16 @entity5019 @entity10639 @entity143 @entity35 @entity5542
We have used immunocytochemical detection of @entity5019 expression (FOS-like immunoreactivity, FLI) to establish the site of action of @entity5542 ( @entity5542 ) in neonatal @entity35 in a model of lesion-induced precocious puberty. The primary target appears to be the hypothalamic arcuate nucleus (ARC) but other circumventricular organs (CVO) are also affected (e.g. subfornical organ). Single injections of @entity5542 (1-4 mg/g single dose, postnatal day 2 (P2)) which result in precocious puberty induce an area of @entity4 , surrounded by a ring of FLI in the basal hypothalamus. In contrast, a maximal sub-lethal dose of @entity143 ( @entity1024 ; 3 mg/kg) which produces a different pattern of ARC FLI, without @entity4 , has no effect on puberty. Multiple doses of @entity5542 (4 mg/g P2, P4, P6, P8), consistent with severe @entity16 and resultant sterility, markedly attenuates the FLI response by P8, with no visible @entity4 following the final injection. In efforts to block the effect of @entity5542 , pretreatment with the @entity143 receptor-specific antagonist @entity3390 ( @entity3390 ) prevented the appearance of @entity4 , as well as the onset of precocious puberty. However, @entity3390 did not completely eliminate the FLI, but transformed the pattern of staining so that the original @entity4 area now contained many FOS-positive cells. This remaining @entity5542 -induced FLI could not be eliminated by higher doses of @entity3390 or by the non- @entity143 antagonist @entity10639 ( @entity10639 ). The combination of @entity3390 and @entity10639 was also ineffective. @entity3390 or @entity10639 had no effect on FLI when injected alone (i.e., without @entity5542 ) or in combination. The receptor which mediates @entity5542 -induced @entity5019 expression, in the presence of @entity3390 or @entity10639 , needs to be identified. We conclude, in conjunction with our previous work, that @entity5542 induces precocious sexual maturation via an @entity3390 -sensitive mechanism associated with an @entity4 response of the basal hypothalamus. Whether the appearance of @entity4 is indicative of an excitotoxic action of @entity5542 , resulting in the removal of neurons inhibitory to sexual maturation, remains to be established.
