Modulation of gonadotrophin-releasing hormone secretion by an endogenous circadian clock

The mechanisms mediating positive feedback effects of oestradiol on pre-ovulatory gonadotrophin releasing-hormone (GnRH) surge generation in female mammals, although well-explored, are still incompletely understood. In addition to binding to and signalling through classical nuclear receptor-mediated pathways in afferent hypothalamic neurones, recent evidence suggests that ovarian steroids may use membrane-bound receptors or nonclassical signalling pathways to directly influence cell function leading to the generation of GnRH surge secretion. We review recent investigations into the role of the endogenous molecular circadian clock on modulation of GnRH gene expression and neuropeptide secretion, and will explore potential molecular mechanisms by which ovarian steroids may directly induce secretory changes at the level of the GnRH neurone, examining closely whether circadian clock gene oscillations may be involved.