|dc.contributor.author||Simony Conesa, Fabian Jesus||
|dc.description.abstract||Kisspeptin is synthesised in the brain in known regions such as the arcuate
nucleus (ARC) and anteroventral periventricular nucleus (AVPV). Kisspeptin has been
classified as a key player in puberty and acts centrally in the upstream regulation of
GnRH neurone secretion via Kiss1 receptors (Kiss1r) to elicit release of GnRH peptide
for further stimulation of LH secretion from the pituitary and consequently of the
gonads to trigger spermatogenesis, follicle development, and sex steroid synthesis. The
KNDy (kisspeptin/neurokinin B/dynorphin) compendium of neurones in the ARC hints
at the possible site of the GnRH pulse generator. Moreover, Kiss1 cells in different
rodent brain areas respond to the absence of circulating steroids in castrate models.
Projections of Kiss1 neurones are found throughout the brain and other kisspeptinergic
populations exist in important areas that regulate metabolism, the circadian rhythm, and
stress. Taken together, these observations suggest that the scope of kisspeptin actions is
not only limited to the modulation of reproductive function and different Kiss1 cell
populations in several brain regions implies association with major
neuropeptides/neurotransmitters and involvement in other physiological processes.
Firstly, the immunocytochemical protocol and antiserum were optimized and
validated to assess true kisspeptin immunoreactive detection of cells and fibres.
Kisspeptin cells were found in specific areas and fibres were located virtually
everywhere throughout the rat forebrain. Kisspeptin neurones were predominantly based
in the ARC, AVPV, medial amygdala, bed nucleus of the stria terminalis and other
hypothalamic regions. Sex steroid regulation of Kiss1 neurones was then investigated by examining the
effects of a chemical castration on those with and without steroid rescue. GnRH
antagonist s.c. injection down-regulated the number Kiss1 neurones in various brain
regions while it enhanced the number of cells in the ARC Kiss1 population.
Testosterone replacement reversed the antagonist effects on Kiss1 neurones. LH plasma
concentration decreased in rats injected with the GnRH antagonist with or without
testosterone administration. These studies therefore confirm importance of sex steroids
on the different kisspeptin populations.
Then, the effects of fasting and re-feeding on Kiss1 neurones in the ARC, rostral
part of the third ventricle (RP3V), and dorsomedial nucleus (DMN) were investigated.
Re-feeding after a 24 hour fast induced no Fos expression in RP3V Kiss1 neurones and
very mild Fos activation in ARC and DMN neurones.
Thus, Kiss1 cells are found in various brain regions whereby distinct
physiological actions occur and each individual population responds differently to the
effects of steroid and metabolic regulation.||en_US
|dc.publisher||The University of Edinburgh||en_US
|dc.relation.hasversion||Sonigo, C, Bouilly, J, Carré, N, Tolle, V, Caraty, A, Tello, J, Simony-‐Conesa, F-‐J, Millar, R, Young, J & Binart, N 2012, ‘Hyperprolactinemia-‐induced ovarian acyclicity is reversed by kisspeptin administration’, Journal of Clinical Investigation, vol. 122, no. 10, pp. 3791–3795.||en_US
|dc.title||Neuroanatomical distribution and properties of Kiss1 neurones in male rats||en_US
|dc.type||Thesis or Dissertation||en_US
|dc.type.qualificationname||MPhil Master of Philosophy||en_US