Oral Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

A novel role for ghrelin in stress and infertility (#133)

Luba Sominsky 1 , Alita Soch 1 , Ilvana Ziko 1 , Madeleine R Di Natale 1 , Simone N De Luca 1 , Sarah J Spencer 1
  1. School of Health and Biomedical Sciences, RMIT University, Melbourne

Infertility has become alarmingly common, with 70 to 80 million couples worldwide currently experiencing infertility, including 1 in 6 Australian couples. Chronic stress can reduce fertility, even in normally-fertile men and women. However, attempts to isolate single causal links between stress and infertility have not yet been successful due to their multi-faceted aetiologies. The gut-derived hormone ghrelin regulates stress and plays a crucial role in fertility. It may therefore be pivotal in the integration of the hypothalamic-pituitary-adrenal (HPA) and –gonadal (HPG) axes. Here, we hypothesised that chronic stress would lead to deleterious effects on reproductive function that are mediated by acyl ghrelin-induced activation of the growth hormone secretatogue receptor (GHSR). C57BL/6J female mice were given 30 min of daily chronic predator stress for 4 weeks or no stress, and administered daily with GHSR antagonist (D-Lys3; 2.74 μg/kg, i.p.) or saline. Chronic predator stress led to significant HPA axis disruption in the absence of the GHSR antagonist, reducing relative saccharine consumption in a saccharine preference test, suppressing circulating corticosterone, and increasing circulating growth hormone levels. The effects on saccharine preference and growth hormone were both rescued by the GHSR antagonist. These effects of chronic stress were accompanied by a substantial increase in circulating acyl ghrelin that was not affected by the GHSR antagonist. Importantly, chronic stress robustly reduced the size of the primordial follicle pool, and this was mitigated by GHSR antagonism. These data suggest that chronic stress-induced increase in acyl ghrelin may act as a crucial neuroendocrine link between stress and reproductive dysfunction that can be pharmacologically targeted to mitigate the negative effects of stress on fertility.