Why pulsatile secretion matters for interpreting secretagogue claims

Why pulsatile secretion matters for interpreting secretagogue claims — that is the question, and I have not found it answered plainly anywhere I have looked.

A follow-up question about pulsatile secretion that I did not know to ask the first time.

The earlier thread answered what I asked. What I should have asked is below, and I think it is the one that matters.

Worth separating two things that the opening post runs together.

Ipamorelin is usually described as selective in that it produces less of an effect on cortisol and prolactin than earlier compounds in the family. Selective is a relative claim and the comparison group matters.

I would treat that as a working assumption and revisit it.

Following this. I have the same question and no better information than the first post.

Growth hormone secretagogues act on the ghrelin receptor or on the growth hormone releasing hormone receptor rather than supplying growth hormone, which is the distinction that matters for anyone reading the literature.

Picking up post #4: that is the part I would want checked first.

Reading a rodent study on a secretagogue without over-extrapolating: rodent studies can show a mechanism is plausible. They cannot show magnitude of effect in humans or safety profile in humans. That gap is larger for secretagogues than for incretin agonists because the human evidence is thinner.

Noting that the question and the thing people usually mean by it are different.

Ipamorelin selectivity claims originate in preclinical characterisation and are reasonably well supported for what they claim: less effect on cortisol and prolactin than earlier GHRPs. Whether that translates to something clinically meaningful is a different question from whether the selectivity is real.

Pulsatile secretion matters because growth hormone is secreted in pulses, not continuously. A single post-dose growth hormone level is nearly uninterpretable. Assessing this class properly requires serial sampling or an integrated measure like IGF-1, and almost nothing published online does either.

GHRH analogues versus ghrelin mimetics are often conflated but they are different mechanisms. GHRH analogues (like CJC-1295) cause the pituitary to release growth hormone. Ghrelin mimetics (like GHRPs) act on the ghrelin receptor directly. The effect on growth hormone secretion is similar but the mechanisms are distinct.

Two people can read the same figure differently here and both be reasonable.

What a well-designed human trial of a secretagogue would look like: randomised, placebo-controlled, adequate sample size, IGF-1 as primary outcome, muscle and strength as secondary outcomes, adequate follow-up duration. Very few secretagogue trials meet that description.