Physiological significance of the rhythmic secretion of hypothalamic and pituitary hormones

The various hypothalamic-pituitary-end-organ/gland axes are central to the regulation of mammalian homeostasis. These have a core role in integrating the response of both endocrine and nervous systems to external and internal stimuli, by means of multi-level signalling through negative and positive feedback loops. The content of these hormonal signals is overwhelmingly conveyed in a rhythmic secretory pattern (frequency modulation of signal) that is energetically more efficient in transmitting neuroendocrine signals than the alternatives (modulation of signal by amplitude or by total area-under-curve). These rhythmic neuroendocrine secretions are individually distinct but the majority display a common feature of low-level basal secretion with superimposed pulsatile rhythms. The underlying mechanisms contributing to this unique rhythmic secretion are complicated and incompletely understood, but are beginning to be better defined as a result of several elegant studies performed in recent years. In some cases, signal transduction in the target tissue is critically dependent upon a pulsatile input, but in others the observed pulsatility is a downstream echo of obligate pulsatility exhibited by a higher-level control hormone. Thus, the gonads are presented with a pulsatile gonadotrophin signal, not because this is essential to gonadotrophin action (the same level of stimulation can be elicited by a continuous input), but as a downstream consequence of pulsatile GnRH-mediated stimulation of pituitary gonadotrophs. By contrast, rhythmicity of signal is embedded at all levels of the hypothalamo-pituitary-adrenal axis. Hypothalamic-pituitary rhythmic secretions are influenced by various internal and external inputs such as age, gender, sleep and wakefulness, food intake, light (photoperiod) or exposure to stress. Understanding the physiological significance of the rhythmic secretion of hypothalamic and pituitary hormones has the potential to provide insights into disease mechanisms, to validate diagnostic tests and, ultimately, to help develop novel therapeutic interventions. This chapter will overview the physiological basis of rhythmic secretion of hypothalamic and pituitary hormones, principally in humans and, by reference to specific examples, describe the various feedback loops and internal and external stimuli that precisely determine these neuroendocrine secretory patterns.