Pulsatile GH Secretion

Growth hormone is not secreted continuously. Frequent sampling over 24 hours shows on the order of ten discrete bursts, each lasting tens of minutes, separated by intervals in which concentrations fall to the detection limit. The pattern comes from the reciprocal rhythm of hypothalamic GHRH and somatostatin: secretion occurs when GHRH drive meets a withdrawal of somatostatin, and the trough between pulses is active inhibition, not absence of stimulus. Deconvolution separates burst frequency, burst mass and basal secretion, which respond differently to age, sex and adiposity.

The pattern itself carries information the total does not. Men secrete in tall, well-separated pulses; women secrete more often with higher interpulse concentrations, giving a profile closer to continuous exposure. In rodents this waveform difference, acting through pulsatile versus sustained STAT5b activation, drives sexually dimorphic hepatic gene expression, and continuous infusion of the same daily amount produces a different transcriptional response from pulses. Adiposity flattens pulses; slow-wave sleep amplifies them.

The practical consequence is that a random growth hormone measurement is uninterpretable in either direction. A healthy adult sampled at a peak can exceed an untreated acromegalic sampled at a nadir, which is why diagnosis rests on provocation, suppression or IGF-1 as a time-integrated proxy, never a single concentration.

Pulsatility is also the strongest pharmacological argument distinguishing secretagogues from injected growth hormone, and it is routinely overstated. Preserving a pulsatile waveform is biologically meaningful, but no trial has shown that it translates into better clinical outcomes or a better safety profile in humans, and a secretagogue given often enough to keep concentrations elevated has abandoned the property being claimed for it.