Zmora, N., Stubblefield, J., Golan, M., Servili, A., Levavi-Sivan, B., and Zohar, Y. (2014) The Medio-Basal Hypothalamus as a Dynamic and Plastic Reproduction-Related Kisspeptin-gnrh-Pituitary Center in Fish. Endocrinology. 155(5):1874-86.
Kisspeptin regulates reproductive events, including puberty and ovulation, primarily via GnRH neurons. Prolonged treatment of pre-pubertal striped bass females with Kiss1 or Kiss2 peptides failed to enhance puberty but suggested a gnrh-independent pituitary control pathway. Kiss2 inhibited, but Kiss1 stimulated FShβ expression and gonadal development, although hypophysiotropic gnrh1 and gnrh receptor expression remained unchanged. In situ hybridization and immunohistochemistry on brains and pituitaries revealed a differential plasticity between the two kisspeptin neurons. The differences were most pronounced at the pre-spawning phase in two regions along the path of gnrh1 axons: the nucleus lateralis tuberis (NLT) and the neurohypophysis. Kiss1 neurons appeared in the NLT and innervated the neurohypophysis of pre-spawning males and females, reaching Lh gonadotropes in the proximal pars distalis. Males, at all reproductive stages, had Kiss2 innervations in the NLT and the neurohypophysis, forming large axonal bundles in the former and intermingling with gnrh1 axons. Unlike in males, only pre-ovulatory females had massive NLT-neurohypophysis staining of kiss2. Kiss2 neurons showed a distinct appearance in the NLTv-equivalent region only in spawning zebrafish, indicating that this phenomenon is wide-spread. These results underscore the NLT as important nuclei for kisspeptin action in two facets: 1) kisspeptin – gnrh interaction: both kisspeptins are involved in the regulation of gnrh release, in a stage- and sex-dependent manner, especially at the pre-spawning phase and 2) gnrh-independent effect of Kiss peptides on the pituitary, which together with the plastic nature of their neuronal projections to the pituitary, implies that a direct gonadotropic regulation is plausible.