Endocrine Abstracts

Biological clocks drive the physiology and behaviour of all organisms, from bacteria to humans. Much attention has focused on the circadian 24 h clock, and rapid progress made in defining key molecular components that regulate our rhythmic physiology. The circadian clock also drives a linked timing system that controls annual cycles of hormone secretion and metabolism, this is most evident in wild species, such as hibernating mammals. Annual cycles are also key feature of domesticated animals, where seasonal clocks drive reproduction, growth and behaviour. Remarkably, a hitherto under-investigated pituitary structure – the pars tuberalis (PT) – appears to be central to the generation of such annual cycles. The PT can measure day length, encoded by nocturnal secretion of melatonin hormone, and TSH of PT origin drives an adjacent circuit regulating thyroid hormone metabolism in the hypothalamus. Thyroid hormone (tri-iodothyronine) activation in the brain leads to altered neuroendocrine activity and rhythmic control of annual reproductive hormones.

In this talk, I will summarise the current state-of-the art investigations of this exciting new timing circuit. I will show that an ancient photoreceptor gene has been co-opted to drive summer-like responses in this tissue, leading to dramatic re-modeling of cells in this endocrine tissue. Re-modeling of epigenetic circuits is likely in this system and I will discuss how clock-controlled methylation/demethylation may lead to long-term changes in neuroendocrine function and annual cycles.

What of humans? Very little is known of the underlying causal mechanisms driving pituitary pathology and endocrine dysfunction. I propose that we may gain important insight into human disease by studying how long-term rhythm generation – driven by clocks – may underpin normal physiology and speculate that perhaps dysregulation of these circuits may also lead to pathology in humans.