Developmental Changes in Hypothalamic Kiss1 Expression during Activation of the Pulsatile Release of Luteinising Hormone in Maturing Ewe Lambs

Abstract

Onset of puberty is characterised by a marked increase in the frequency of release of gonadotrophin-releasing hormone (GnRH) and luteinising hormone (LH). The Kiss1 gene plays a critical role in pubertal development, and its product, kisspeptin, stimulates GnRH and LH release. In the present study, we tested the hypothesis that Kiss1 gene expression in the preoptic area (POA) and hypothalamus increases during maturation of the reproductive neuroendocrine axis in association with increased LH pulsatility. Ovariectomised, oestradiol-replaced lambs were euthanised at 25, 30 and 35 weeks of age. Blood samples were collected before euthanasia to characterise the pattern of LH release. Kiss1 mRNA was detected in coronal sections of the POA and hypothalamus and Kiss1-expressing cells were identified on the basis of silver grain density. The mean number of Kiss1-expressing cells in the POA/periventricular (PeV) areas increased from 25 to 30 weeks of age. No further increase at 35 weeks of age was observed, and the changes in Kiss1 expression in the POA/PeV were independent of changes in LH pulse frequency. The mean number of Kiss1-expressing cells in the arcuate (ARC) nucleus did not differ among age groups, although it was greater in the middle ARC of lambs exhibiting increased frequency of LH release. The density of silver grains per cell did not differ among groups in any of the areas studied. The results obtained indicate that the Kiss1 gene is activated in the POA/PeV and ARC of ewe lambs during juvenile development, and that kisspeptin neurones in the middle ARC, in particular, are involved in the acceleration of pulsatile LH release during maturation of the reproductive neuroendocrine axis in ewe lambs.

Localization of kisspeptin neurons in the hypothalamus of peripubertal female lambs; possible connection with gonadotrophin releasing hormone and neuropeptide Y neurons

“…In contrast, in 6-month-old prepubertal female lambs, only single and very lightly stained kp perikarya have been observed in this hypothalamic area (Nestor et al, 2012), similarly to the observations in peripubertal lambs in our study. High expression of kp mRNA has also been observed, however (Redmond et al, 2011). These data suggest that during prepubertal development of lambs, the post-translational processing of kp does not occur in the kp perikarya distributed in the MPOA-AHA.…”

“…Recent data obtained on prepubertal (5-to 6-month-old) and post pubertal (9-month-old) female lambs also showed a predominant population of kp perikarya in the ARC nucleus that increased with age (Nestor et al, 2012). The expression of Kiss1 mRNA is also activated in the ARC nucleus of ewe lambs during juvenile development from 25-35 weeks of age (Redmond et al, 2011). It was demonstrated on ovariectomized ewes treated acutely with E2 that the number of kp arcuate cells co-labelled with c-fos increased 6-fold, so the authors conclude that these kp neurons are involved in generating the positive feedback preovulatory GnRH/LH surge (Smith et al, 2009b).…”

“…It was demonstrated on ovariectomized ewes treated acutely with E2 that the number of kp arcuate cells co-labelled with c-fos increased 6-fold, so the authors conclude that these kp neurons are involved in generating the positive feedback preovulatory GnRH/LH surge (Smith et al, 2009b). It was also demonstrated that mainly the subpopulation of arcuate kp neurons is involved in the increased input to GnRH neurons leading to puberty in sheep (Redmond et al, 2011). In conclusion, the visualization and high number of kp arcuate perikarya, without inhibition of axonal transport by colchicine treatment, observed in the present study, may result from their increased secretory activity in the period preceding the first ovulation.…”

Role of Adipose Secreted Factors and Kisspeptin in the Metabolic Control of Gonadotropin Secretion and Puberty

“…Furthermore, expression of KiSS-1 in the ARC and the rostral preoptic area are differentially regulated by gonadal steroids (Estrada et al, 2006;Smith et al, 2005Smith et al, , 2007Tomikawa et al, 2010). It has recently been shown that increased LH pulsatility during sexual maturation in the ewe is associated with a reduction in the suppressive effects of estradiol on KiSS-1 expression (Redmond et al, 2011). The fundamental importance of kisspeptin in the onset of puberty raises the question as to whether kisspeptin has a central role in the timing of pubertal events associated with metabolic state or body energy reserves.…”

GENOMICS SYMPOSIUM: Using genomic approaches to uncover sources of variation in age at puberty and reproductive longevity in sows

“…The hypothalamic ARC contains neurons that are involved in regulating pubertal onset and maintenance of estrous cycles through the control of gonadotropin secretion Redmond et al, 2011). High-throughput RNA sequencing reads were obtained from the ARC from gilts representing pre-and postpubertal time points and early and late pubertal gilts fed 3 different dietary treatments.…”