Gonadotropin-Inhibiting Hormone Rises and Luteinizing Hormone Falls in Male Rats Exposed to Stress

Abstract

Many animals, including rats and humans, show reproductive abnormalities after experiencing stress. Multiple interactions between the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis are responsible for the negative effects of stress on reproduction. It has recently been reported that the gonadotropin-inhibitory hormone (GnIH) in quail is a negative regulator of the HPG axis, and that its orthologous neuropeptides, RFamide-related peptides (RFRPs), have been found in rodents and primates. However, whether or whether GnIH/RFRPs affect HPG axis activity while under pressure is not well understood. Here we demonstrate that adult male rats' RFRP expression in the dorsomedial hypothalamus (DMH) increases in response to acute and chronic immobilization stress, and that this rise is accompanied by a reduction in HPG activity. Moreover, our results show that the normal stress-induced upregulation of RFRP expression is blocked by adrenalectomy. Around 53% of RFRP cells have glucocorticoid (GC) receptors, according to immunohistochemistry, indicating that adrenal GCs may directly act on RFRP cells to modulate the stress effect. It is hypothesized that GnRH-secreting neurons play a mediating role between stress and the central regulation of reproduction. Our findings demonstrate that elevated RFRP contributes to hypothalamic regulation of reproductive function by increasing the activity of GCs in the adrenal glands in response to stress. These novel insights into the HPA-HPG connection imply that the role of GnIH/RFRP has to be addressed in future investigations of the interplay between stress and the reproductive system, shifting the paradigm for research into stress-related reproductive dysfunction and infertility.