Regulation of the gonadotropin‐releasing hormone neuron during stress

Abstract

The effect of stress on reproduction and gonadal function has captivated investigators for almost 100 years. Following the identification of gonadotropin-releasing hormone (GnRH) 50 years ago, a niche research field emerged fixated on how stress impairs this central node controlling downstream pituitary and gonadal function. It is now clear that both episodic GnRH secretion in males and females and surge GnRH secretion in females are inhibited during a variety of stress types. There has been considerable advancement in our understanding of numerous stress-related signaling molecules and their ability to impair reproductive neuroendocrine activity during stress. Recently, much attention has turned to the effects of stress on two populations of kisspeptin neurons: the stimulatory afferents to GnRH neurons that regulate pulsatile and surge-type gonadotropin secretion. Indeed, future work is still required to fully construct the neuroanatomical framework underlying stress effects, directly or indirectly, on GnRH neuron function. The present review evaluates and synthesizes evidence related to stress-related signaling molecules acting directly on GnRH neurons. Here, we review the evidence for and against the action of a handful of signaling molecules as inhibitors of GnRH neuron function, including corticotropin-releasing hormone, urocortins, norepinephrine, cortisol/corticosterone, calcitonin gene-related peptide and arginine-phenylalanine-amide-related peptide-3.

Interactions between β‐endorphin and kisspeptin neurons of the ewe arcuate nucleus are modulated by photoperiod

“…Indeed, infusion of the μ opioid receptor antagonist, β‐funaltrexamine, blocks stress‐associated LH suppression induced by electric footshocks in rats 48 . Whether or not BEND may involve CRH neurons to modulate LH release in sheep remains to be established but, in contrast with other species, it was previously shown in steroid‐replaced ewes that central administration of 20 nmol of CRH stimulates LH release 50 ; therefore, the stimulation of KP neurons following BEND infusion may pass through activation of CRH release that, in turn, will activate KNDy neurons but, as stated in a recent review, 51 CRH effect on LH release may be extremely complex in the ovine species because it depends on the gonadal status and the time of the ovarian cycle.…”

Neuromodulatory Effects Induced by the Association of Moringa oleifera Lam., Tribulus terrestris L., Rhodiola rosea Lam., and Undaria pinnatidifida Extracts in the Hypothalamus

“…The secretion of GnRH in females is reduced in presence of stress stimuli. [25] Additionally, the stimulation of serotonin release, as in the case of anti-depressant drug administration, is followed by reduced GnRH activity; thus explaining, at least in part, the reduction of libido. [52] In this context, the increased GnRH gene expression induced by the formulation may contribute not only to improve the resistance towards the stress, but also to prevent the reduction of libido that could occur with a stimulation of the serotoninergic pathway.…”

“…[20,21] Therefore, the present study evaluted the modulatory effects of a commercial formulation including water extracts from R. rosea, M. oleifera, and U. pinnatifida on hypothalamic factors involved in fatigue and response to the stress, among which CRH, NPY, orexin A, and serotonin. [4,[22][23][24][25] The activity of the formulation was also evaluated in terms of intrinsic antioxidant properties, alongside with content of specialised metabolites, namely phenolic and flavonoid compounds. These compounds are known to exert protective and neuromodulatory effects.…”

Pathogenesis of the crosstalk between reproductive function and stress in animals—part 1: Hypothalamo–pituitary–adrenal axis, sympatho‐adrenomedullary system and kisspeptin

“…Other mechanisms linking HPA, metabolic and reproductive systems have been discovered. This includes kisspeptin and the gonadotropin‐inhibitory hormone (GnIH) (McCosh et al, 2022). Kisspeptin is a potent regulator of the pulsatile GnRH secretion and of the surge LH release in horses (Magee et al, 2009; McGrath et al, 2016), pigs (Lents et al, 2008), dogs (Albers‐Wolthers et al, 2016) sheep and bovine (Caraty & Franceschini, 2008).…”