Brainstem noradrenergic neuronal populations: dual effects on regulating GnRH and LH secretion

Abstract Noradrenergic neurons are a brain network that integrate viscero-sensorial signals to modulate neural and neuroendocrine function. Although it has been known for decades that noradrenergic neural circuits influence neuroendocrine and reproductive function, the cellular and molecular players involved remain largely unknown. The objective of this review is to summarize past and current knowledge regarding the influence of brainstem noradrenergic systems on gonadotrophin-releasing hormone (GnRH) and gonadotrophin secretion. The main noradrenergic cell groups A1, A2 and A6, known as the ventrolateral medulla, nucleus of the solitary tract and locus coeruleus, respectively, are involved in the control of reproductive neuroendocrine secretion. Current evidence suggests that brainstem noradrenergic circuits promote the generation and maintenance of the luteinizing hormone (LH) surge in both spontaneous (rats, sheep) or induced ovulators (rabbit, ferret). In contrast, recent studies have established that LH pulsatile secretion is suppressed by specific activation of brainstem noradrenergic cell groups. The duality of the GnRH/LH response to noradrenaline reflects the inherent complexity of hindbrain noradrenaline neurons, which are responsive to stressors and gonadal steroids (i.e. estradiol) and co-express a variety of neurotransmitters and neuropeptides. Therefore, elucidating the organization and functionality of brainstem noradrenergic systems will provide targets for controlling reproduction and understanding the interconnection with stress.