Pulsatile secretion is a biochemical phenomenon observed in a wide variety of cell types, in which chemical products are secreted in a regular pattern. The most common cellular products observed to be released in this manner are intercellular signaling molecules such as hormones or neurotransmitters. The most common examples of hormones that are secreted pulsatilely include insulin, thyrotropin, TRH, gonadotropin-releasing hormone and growth hormone. In the nervous system, pulsatility is observed in oscillatory activity from pacemakers and central pattern generators. Pulsatile activity is critical to the function of many hormones in order to maintain the delicate homeostatic balance necessary for essential life processes, such as development and reproduction. Pulsatile secretion can be critical to hormone function, as evidenced by the case of GnRH agonists, which cause functional inhibition of the receptor for GnRH due to profound downregulation in response to constant stimulation. Pulsatility may function to sensitize target tissues to the hormone of interest and upregulate receptors, leading to improved responses. This heightened response may have served to improve the animal's fitness in its environment and promote its evolutionary retention. Pulsatile secretion in its various forms is observed in:
Hypothalamic-Pituitary-Gonadal axis related hormones
LH is released from the pituitary gland along with FSH in response to GnRH release into the hypophyseal portal system. Pulsatile GnRH release causes pulsatile LH and FSH release to occur, which modulates and maintains appropriate levels of bioavailable gonadal hormone: testosterone in males and estradiol in females. In females the levels of LH is typically 1–20 IU/L during the reproductive period and is estimated to be 1.8–8.6 IU/L in males over 18 years of age.
Glucocorticoids
Regular pulses of glucocorticoids, mainly cortisol in the case of humans, are released regularly from the adrenal cortex following a circadian pattern in addition to their release as a part of the stress response. Cortisol release follows a high frequency of pulses, with amplitude being the primary variation in its release. Glucocorticoid pulsatlity has been observed to follow a circadian rhythm, with highest levels observed before waking and before anticipated mealtimes. This pattern in amplitude of release is observed to be consistent across vertebrates. Studies done in humans, rats, and sheep have also observed a similar circadian pattern of release of adrenocorticotropin shortly preceding the pulse in the resulting corticosteroid. It is currently hypothesized that the observed pulsatility of ACTH and glucocorticoids is driven via pulsatility of corticotropin-releasing hormone, however there exists little data to support this due to difficulty in measuring CRH.
Insulin
Oscillations of intracellular calcium concentration in beta cells within the pancreas produces a basal pulsatile secretion of insulin form the pancreas. Secretion pulses emanating form free beta cells not located within an islet of Lagerhans have been observed to be highly variable. Beta cells within an islet, however, become synchronized via electrical coupling resulting from gap junctions and osculate more regularly. ATP signalling has also been proposed as a method of coordination between beta cells. Pulsatile insulin secretion from individual beta cells is driven by oscillation of the calcium concentration in the cells. In beta cells lacking contact, the periodicity of these oscillations is rather variable. However, within an islet of Langerhans, the oscillations become synchronized by electrical coupling between closely located beta cells that are connected by gap junctions, and the periodicity is more uniform. In addition to gap junctions, pulse coordination is managed by ATP signaling. α and δ cells in the pancreas also share secrete factors in a similar pulsatile manner.
