This review explains that the brain’s GnRH hormone, which controls reproduction, is regulated by upstream neurons rather than directly by sex hormones. Kisspeptin neurons act as the main bridge for sex‑steroid feedback to GnRH, while GnIH neurons can suppress GnRH and also affect the pituitary. The paper highlights these pathways as key steps in how stress, nutrition, and seasons influence reproductive function.

The reproductive system is controlled by gonadotropin releasing hormone (GnRH) secretion from the brain, which is finely modulated by a number of factors including gonadal sex steroids. GnRH cells do not express estrogen receptor α, but feedback is transmitted by neurons that are at least 'one step back' from the GnRH cells. Modulation by season, stress and nutrition are effected by neuronal pathways that converge on the GnRH cells. Kisspeptin and gonadotropin inhibitory hormone (GnIH) neurons are regulators of GnRH secretion, the former being a major conduit for transmission of sex steroid feedback. GnIH cells project to GnRH cells and may play a role in the seasonal changes in reproductive activity in sheep. GnIH also modulates the action of GnRH at the level of the pituitary gonadotrope. This review focuses on the role that kisspeptin and GnIH neurons play, as modulators that are 'one step back' from GnRH neurons.