Adverse early environments can have a profound and lifelong influence on stress reactivity. Exposure of neonatal rats to stress, e.g. an immunological challenge of lipopolysaccharide (LPS), programs long-term changes in hypothalamo-pituitary-adrenal activity with increases in basal corticosterone pulse frequency and amplitude as well as marked increases in stress-induced corticosterone release in adulthood. This neonatal challenge also impacts on the hypothalamo-pituitary-gonadal (HPG) axis, resulting in delayed puberty and disruption to ovarian cyclicity which persisted into adulthood. The up-regulation of ovarian low-affinity receptor of nerve growth factor (p75NGFR), a key marker of raised sympathetic tone, may account for the observed increased thickness of the theca interna and reduced follicle reserve. The down-regulation of hypothalamic kisspeptin, identified as an essential gatekeeper of pubertal onset and gonadotrophic hormone secretion, could provide a mechanism for the observed delay of puberty and may be the first manifestation of more long-lasting changes to the HPG axis, namely disturbed ovarian cycles and sensitisation to stress-induced suppression of the GnRH pulse generator in adulthood. In the adult, considerable progress has been made concerning the mechanisms underlying corticotrophin-releasing factor (CRF)-induced suppression of GnRH pulse generator activity, including novel sites of action within key brain regions commonly associated with stress responsivity. There is a differential involvement of CRF receptor type 1 and 2 in stress-induced suppression of the GnRH pulse generator, which is both stressor and brain loci specific. Moreover, the observed CRF or stress-induced down regulation of kisspeptin and its receptor (Kiss1r) expression in hypothalamic regions critical for the control of LH secretion suggests a key role for the integration of CRF and kisspeptin signalling in the regulation of the GnRH pulse generator. We have recently shown a novel role for CRF in the timing of puberty and the up-regulation of amygdaloid CRF with delayed puberty in neonatal-LPS treated rats suggests this limbic brain structure may contribute to the developmental cues that drive and modulate the kisspeptin system critical for reproduction.