Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2013

Mechanism for stress-induced suppression of reproduction: chronic pseudo-stress increases gonadotropin inhibitory hormone (GnIH) gene expression and neuronal input to gonadotropin releasing hormone (GnRH) cells. (#8)

Danielle Bartolini 1 , Belinda A Henry 1 , Iain J Clarke 1
  1. Monash University, Clayton, Vic, Australia

Stress reduces GnRH and gonadotropin secretion in sheep, due to a rise in cortisol levels1. The mechanism for this suppressive effect is unknown. One negative regulator of GnRH neurons and gonadotropes is GnIH, which is produced in neurons of the dorsomedial nucleus of the hypothalamus2. GnIH cells are not activated during acute stress3, but the effect of chronic stress is unknown. Here, we tested the hypothesis that GnIH neurons relay the effect of chronic pseudo-stress to GnRH neurons.

Ovariectomised ewes (n=8) received daily i.m. injections (0.5mg) of a long-acting synthetic adrenocorticotrophin (Synacthen Depot) or vehicle for 4 weeks, as described previously4. Synacthen treatment increased cortisol levels (p<0.01)4 and the earlier study also showed that the Synacthen treatment reduced LH secretion4.  The brains were harvested and processed for in situ hybridization and immunohistochemical analysis.  In situ hybridization was performed with a 35S-labelled riboprobe, enabling counts of GnIH cells and GnIH gene expression/cell (silver grains). In situ hybridization analysis showed that Synacthen treatment increased the mean (±SEM) GnIH cell number in the DMH (564±64 vs 314±0.5 in vehicle treated animals), with no difference in the level of expression/cell (silver grains/cell; Synacthen - 1588 ± 303, vehicle - 2469 ±734). Double label immunohistochemistry enabled measurement of the number of GnRH cells contacted by projections from GnIH cells. Synacthen treatment increased (p<0.01) the percentage of GnRH cells receiving GnIH contact (Synacthen - 16%±1.9% vs vehicle - 2.9±1.7%).

These data show that chronic pseudo-stress increases the function of GnIH cells as well as the degree to which GnIH cells provide input to GnRH cells. Accordingly, GnIH cells may provide a neuronal mechanism, within the brain, whereby stress and elevated cortisol levels negatively impact on reproductive function. Current studies are investigating whether acute and/or chronic pseudo-stress elevates secretion of GnIH into hypophyseal portal blood.

  1. Oakley et al. (2009) Endocrinology150:341
  2. Clarke et al. (2009) Front Neuroendocrinol 30:371
  3. Papagiris et al (2011) J Neuroendocrinol.
  4. Henry et al (2010) Domest Anim Endocrinol 38:46