ResearchSafe

New peptide antagonist blocks the GH receptor itself, not just secretion

Posted by midwest_swims in GH & Growth Peptides - 0 points, 4 comments.

https://www.napleslongevity.com/post/growth-hormone-peptides

This one jumped out because most stuff on the board is about turning GH up, but this is about turning GH signalling down at the receptor. The researchers made a small helical peptide that binds the GH receptor and blocks it, and it actually lowered IGF-1 in animal models from what I can gather. The interesting bit for me is that they are framing it as a longer acting alternative to current GH antagonists like pegvisomant, which is a big protein drug and a pain to dose.

My take, if anyone has read it more carefully, does this antagonist look like it actually reduces GH action tissue by tissue, or is it a blunt drop everywhere? Because excess GH in acromegaly is the obvious target, but a reversible receptor blocker could also be useful research wise for studying how much of the body comp effects people chase actually come from the GH signal itself versus IGF-1 downstream.

Anyone here looked into receptor level antagonism at all, or is everyone still focused on the secretagogue side?

Comments

  • formerdana: Im honestly more interested in the research side of this than the therapeutic angle. If you can block the receptor in a reversible way, that gives you a proper tool to separate out whats GH driven vs IGF-1 driven, which is a question ive wanted answered for ages. Most of the data people chase is correlational at best. A clean receptor blocker in animals would at least give some mechanism. I havent read the paper closely yet but id want to know if its actually selective for the GHR or if it drag
  • mira_mobility: Yeah the prolactin cross reactivity is exactly what i was going to flag, pegvisomant binds PRLR too and that muddies a lot of older data. If this new peptide stays clean on GHR it could genuinely clean up the mechanistic picture, even if it never makes it past animal work.
  • midwest_swims: Right, that's a on PRLR. I hadn't fully clocked how much of the "GH-specific" data in acromegaly work is actually confounded by prolactin signalling too. If it really is clean on GHR only, then yeah, even just as a research tool it would be useful. Most of what people cite about GH vs IGF-1 effects is muddled because the available blockers aren't selective enough.
  • midwest_swims: Yeah that's actually the part that bugged me too when I skimmed it. The authors mostly just say "selective for GHR" but don't really show binding data against prolactin or related receptors, which like you said is the whole thing pegvisomant gets hammered for. If they're claiming reversible receptor antagonism they should at least run a counter-screen against the prolactin receptor, otherwise it's just marketing. Did you see if they included any off-target binding panel in the supplement? I onl

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