Neuroanatomical connections between kisspeptin neurones and somatostatin neurones in female and male rat hypothalamus: a possible involvement of SSTR1 in kisspeptin release

Abstract

Somatostatin (SST) a neuropeptide involved in the central modulation of several physiological functions, is co-distributed in the same hypothalamic areas as kisspeptin (KP), the most potent secretagogue of the gonadotropin-releasing hormone (GnRH) secretion known to date. As SST infused intracerebroventricularly (icv) evoked a potent inhibition of GnRH release, we explored neuroanatomical relationships between KP and SST populations in male and female rats. For that, intact males and ovariectomised oestradiol-replaced females were killed and their brains processed in order to simultaneously detect KP, SST and synapsin, a marker for synapses. We observed numerous appositions of KP on SST neurones both in female and male arcuate nucleus (ARC) and ventromedial hypothalamus. A large association between SST terminals and KP neurones at the level of the pre-optic area (POA) was also observed in female rats and in a more limited frame in males. Finally, most KP neurones from the ARC showed SST appositions in both sexes. To determine whether SST could affect KP cell activity, we assessed whether SST receptors (SSTR) were present on KP neurones in the ARC. We also looked for the presence of SSTR1 and SSTR2A in the brain of male rats. Brains were processed through a sequential double immunocytochemistry in order to detect KP and SSTR1 or KP and SSTR2A. We observed overlapping distributions of immunoreactive neurones for SSTR1 and KP and counted approximately one third of KP neurones with SSTR1. In contrast, neurones labelled for SSTR2A or KP were often juxtaposed in the ARC and the occurrence of double-labelled neurones was sporadic (<5%). These results suggest that SST action on KP neurones would pass mainly through SSTR1 at the level of the ARC.

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