|State||Accepted/In press - Jun 2010|
Ultradian pulsatile hormone secretion underlies the activity of most neuroendocrine sys- tems, including the hypothalamo-pituitary adrenal (HPA) and gonadal (HPG) axes, and this pulsatile mode of signalling permits the encoding of information through both amplitude and frequency modulation. Thus in the HPA axis, glucocorticoid pulse ampli- tude increases in anticipation of waking, and in the HPG axis changing gonadotrophin- releasing hormone (GnRH) pulse frequency is the primary means by which the body alters its reproductive status during development. The prevalence of hormone pulsatility raises two crucial questions: how are ultradian pulses encoded (or generated) by these systems, and how are these pulses decoded (or interpreted) at their target sites? We have looked at mechanisms within the HPA axis responsible for encoding the pulsatile mode of glucocorticoid signalling that we observe in vivo. We review evidence regard- ing the ‘hypothalamic pulse generator’ hypothesis, and present an alternative model for pulse generation which involves steroid feedback-dependent endogenous rhythmic ac- tivity throughout the HPA axis. We also consider the second question concerning the decoding of hormone pulsatility, taking the HPG axis as a model system, and focussing on molecular mechanisms of frequency decoding by pituitary gonadotrophs.
Additional information: A preprint document accepted for publication in the Journal of Neuroendocrinology. The definitive version is available at www3.interscience.wiley.com
Sponsorship: EPSRC EP/E032249/1
- decoding, pulsatile hormone secretion, encoding, mathematical modelling, hpa axis, gonadotrophin-releasing hormone, glucocorticoid hormones, endocrine signalling, ultradian pulsatility, ultradian rhythm