Historical text by DatBTrue, written between 2008 and 2016 and reproduced verbatim. It records what was argued then; it is not dosing guidance and not medical advice. Read the disclaimer.
I think it’s important to start off by visualizing an interesting distinction between peptide hormones such as insulin and growth hormone and the peptide hormone IGF-1. Insulin and Growth Hormone have their own specific storage vesicles within specialize cells or tissue where they may sit and await a command for release. IGF-1 has no such storage compartment. Stated succinctly, Growth Hormone and Insulin are held in storage compartments before release whereas there is no such storage compartment for IGF-1.
This distinction has the consequence that circulating growth hormone and insulin are low under non-stimulated conditions. As a result the signal to the body to go on and do something as a command from growth hormone or insulin derives almost exclusively from controlling the entry rate of those peptide hormones into circulation. When these peptides can be coaxed from their storage areas into circulation they have the opportunity to transmit that signal or command to target tissue. As a consequence of having their own specific storage sites, the signal level that growth hormone is capable of bringing or the signal level that insulin is capable of bringing is primarily regulated by controlling their entry into circulation. It is not controlled by their rate of synthesis.
The synthesis of insulin and growth hormone need not be rapid. The concentration of these two hormones released into circulation is not limited by their rate of synthesis. The body seems to always have plenty at the ready. Enhancement of growth hormone or insulin synthesis is never something we need be immediately concerned.
The signaling commands that insulin and growth hormone bring are only effective if target cells express specific receptors to receive the hormones and capture that signal. So it is rapid changes in hormone concentration together with receptive tissue that initiates the body to do something.
All of this is distinct from the IGF-1 system. There is no gland or storage vesicle for IGF-1. Without a storage component housing complete and ready for release IGF-1, it becomes more dependent on various components to convey it’s signaling command. The synthesis rate is important and IGF-1’s appearance in circulation is slow and dependent on it’s synthesis rate and on how the body chooses to maintain, discard or deliver it.
For IGF-1 the circulation becomes the extracellular storage area and it is maintained, discarded or delivered based on it’s attachment to binding proteins or the ternary complex – Acid labile subunit. These binding proteins and the ternary complex are in a way virtual storage compartments as they maintain IGF-1. The total serum level of IGF-1 depends on both the synthesis rate and the capacity and stability of the aforementioned complexes which act as a buffer.
Growth hormone and Insulin are transmitted to target tissue in a pulse through the bloodstream from their storage units. The bloodstream is merely a means of transmission. For IGF-1 it must rely on the bloodstream to serve as it’s reservoir.
IGF-1 also differs from growth hormone and insulin in that IGF-1 is produced in tissue throughout the body from muscle to brain (even though the liver remains the primary source). As a consequence IGF-1 is best thought of as an autocrine or paracrine IGF1 system even though circulating IGF-1 is often characterizes as endocrine or systemic. In the IGF-1 autocrine/paracrine system local signaling is highly dependent on the local synthesis and release of IGF acting on the producer cell, or its neighbours, by local diffusion. Furthermore local production of specific binding proteins may attract circulating IGF-1 and sequester them, either localizing them to target cells or retaining them in the producer tissue in an extracellular pool from which that cell population may eventually draw from. Proteases which cut off the IGF-1 from the attached binding proteins would free IGF-1 and make them available to the cellular receptors. The appearance of proteases to do this most likely comes from release & activation from damaged cells such as damaged muscle cells from resistance exercise.
IGF-1 once cut off from the local binding protein could either join a local pool of free IGF-1 for local activity or escape the local environment and enter circulation. Binding proteins in circulation would reattach to and buffer the paracrine IGF-1 to prevent the locally generated IGF-1 signaling to spread to other tissues.
Blood tests for circulating IGF-1 do not measure the activity of IGF-1. They are actually measuring the storage reserve. Whereas blood tests for growth hormone and insulin need to be timed correctly they do not measure storage but reveal the amount of peptide in route to activity at that point in time.
Endocrine vs paracrine secretory systems. a) The classical endocrine system, with a gland reserve of hormone and transmission of bursts of hormone release in the bloodstream to stimulate target tissues that selectively express the relevant hormone receptor. b) The endocrine IGF1 system has no primary gland store, but the peptide is constitutively produced from many tissues, with liver being a major source. The bloodstream serves as the IGF reservoir, retaining IGF1 complexed with binding proteins (BPs) and acid labile subunit (ALS) to prevent rapid elimination. A small proportion of free IGF dissociated from these complexes can bind IGF receptors in the target tissues. c) IGF1 is also generated locally in many tissues which are also targets for its action. They also produce binding proteins which may block or enhance IGF1 local action. BP and ALS in the circulation now serve to capture and buffer any locally produced IGF1 escaping to signal elsewhere.