Reduced energy reserves compromise the hypothalamo-pituitary gonadal axis (HPG), but how gonadotropin-releasing hormone (GnRH) neurons in the brain sense metabolic reserves is complex. GnRH neurons do not express leptin receptors but Kiss neurons do so and could transduce and relay metabolic signals to GnRH neurons. Kiss neurons also receive glutamatergic input essential for the pulsatile secretion of GnRH (1). The aim of this study was to examine this network in sheep with reduced bodyweight, in an effort to understand the plasticity that leads to reduced GnRH secretion.
Ovariectomised ewes (n = 5/group) were fed a maintenance diet or a restricted diet for 4 months to reach mean (±SEM) weights of 59.1 ± 0.8 kg and 35.2 ± 1.8 kg respectively. The lean animals displayed reduced pulsatile luteinising hormone secretion, elevated growth hormone secretion and reduced Kiss expression (determined by in situ hybridisation), as shown previously (2,3).
However, there was an 80% increase in the mean (±SEM) number of Kiss immunopositive cell in the arcuate nucleus of the lean animals (60 ± 12 vs 108 ± 5 cells/section, p<0.001), suggesting a reduction in activation and the accumulation of the peptide in perikarya. We also observed a 35% reduction in glutamatergic input to Kiss cells (13.8 ± 0.7 vs 9.09 ± 0.8 contact/cell p<0.001). These changes in synaptic connectivity could explain the reduction in activity of Kiss neurons that would lead to hypogonadotropic condition, since Kiss is a primary stimulator of GnRH secretion. Such plasticity may be due to an altered leptin action on Kiss neurons (3), with lowered levels of circulating leptin in the lean animals or to other metabolic factors, such as insulin, signalling energy status.
References