Feedback from oestradiol (E2) plays a critical role in the regulation of major events in the physiological menstrual cycle including the release of gonadotrophins to stimulate follicular growth, and the mid-cycle luteinising hormone (LH) surge that leads to ovulation. E2 predominantly exerts its action via oestrogen receptor-alpha (ERα), however, as gonadotrophin releasing hormone (GnRH) neurons lack ERα, E2-feedback is posited to be indirectly mediated via upstream neurons. Kisspeptin (KP) is a neuropeptide expressed in hypothalamic KP-neurons that control GnRH secretion and plays a key role in the central mechanism regulating the hypothalamic-pituitary-gonadal (HPG) axis. In the rodent arcuate (ARC) nucleus, KP is co-expressed with Neurokinin B and Dynorphin; and thus, these neurons are termed ‘Kisspeptin-Neurokinin B-Dynorphin’ (KNDy) neurons. ARC KP-neurons function as the ‘GnRH pulse generator’ to regulate GnRH pulsatility, as well as mediating negative feedback from E2. A second KP neuronal population is present in the rostral periventricular area of the third ventricle (RP3V), which includes anteroventral periventricular (AVPV) nucleus and preoptic area neurons. These RP3V KP-neurons mediate positive feedback to induce the mid-cycle luteinising hormone (LH) surge and subsequent ovulation. Here, we describe the role of KP-neurons in these two regions in mediating this differential feedback from oestrogens. We conclude by considering reproductive diseases for which exploitation of these mechanisms could yield future therapies.

Head and neck cancers are largely squamous cell carcinomas derived from the epithelial lining of the structures in the region, and are often classified anatomically into oral, oropharyngeal, nasopharyngeal and laryngeal carcinomas. The region’s component structures serve complex and intricate functions, such as speaking, swallowing and breathing, which are often compromised by these neoplasms. Such lesions may also cause disfigurement, leading to distressing social and psychological issues. Conventional treatments of these neoplasms usually involve surgical intervention with or without chemoradiotherapy. These have shown to be efficacious; however, they can also cause damage to healthy as well as diseased tissue, exacerbating the aforementioned problems. Access to a given region to deliver the treatments is also often a problem, due to the complex anatomical structures involved. The use of photodynamic therapy in the head and neck region has been established for about two decades. In this review, we looked at the basic mechanisms of this intervention, examined its use in common head and neck malignancies and vascular anomalies, and reported on the most recent clinical studies. We further included a clinical guide which can help replicate the use of this technology by any unit. Based on this review, photodynamic therapy has been shown to be efficacious in the treatment of head and neck malignancies and vascular tumours. This therapy can be targeted to the diseased tissue and causes no damage to underlying structures. Recent studies have shown this therapy to be as effective as conventional therapies, without causing major adverse effects.

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