Orderliness of hormone release patterns: a complementary measure to conventional pulsatile and circadian analyses

Pre-eminent features of physiological hormone release include both pulsatile and nyctohemeral elements, which are modulated in normal physiology and often disrupted in pathological states. The pulsatile nature of neurohormone signaling is critical to long-term activation and physiological regulation of many neuroendocrine axes, such as the gonadotropin-releasing hormone (GnRH)–luteinizing hormone (LH)–gonadal axis in men and women. Indeed, a pulsatile but not continuous GnRH signal to gonadotrope cells will preserve physiological biosynthesis and secretion rates of the gonadotropins, LH and follicle-stimulating hormone (FSH) and, in turn, maintain gonadal steroidogenesis and gametogenesis. For the growth hormone-releasing hormone (GHRH)–somatostatin/growth hormone (GH)/insulinlike growth factor-I (IGF-I) axis, pulsatile GHRH release by hypothalamic neurons is also believed to organize episodic GH secretion, as coordinated by prior and concurrent hypothalamic somatostatin tone. Moreover, the pulsatile GH signal activates organ-specific secondmessenger signaling pathways, such as the STAT5b signaling cascade in the liver, with subsequent induction of specific genomic responses in relevant target tissues, which are not induced equivalently by a constant GH stimulus. Non-pituitary hormones (e.g. parathyroid hormone (PTH), insulin, renin) also exhibit a distinctly pulsatile time-course of release. Furthermore, neurohormone secretion often partakes of a nyctohemeral and, in some specific cases, circadian rhythmicity. The 24-h rhythms are assembled in part from day-night amplitude and frequency control of the underlying ultradian (shorter-term) pulsations (1). Recent modeling strategies suggest possible mechanisms linking physiological pulsatility and circadian rhythmicity (2), but far more study will be required to establish the bases for such connectivity in health and disease.