Endocrine Pathway
The Growth Hormone Axis
Growth hormone secretion is governed by two opposing hypothalamic peptides — GHRH (stimulatory) and somatostatin (inhibitory) — modulated by the stomach-derived ghrelin. Pulsatile GH release drives hepatic IGF-1, which mediates most anabolic effects. Synthetic GHRH analogues (sermorelin, CJC-1295) and GHRP-class ghrelin agonists (ipamorelin, GHRP-2) are widely studied in research models of the axis.
Peer-reviewed references
- • Veldhuis JD et al. Endocr Rev (2016) — Pulsatile GH secretion.
- • Sigalos JT & Pastuszak AW. Sex Med Rev (2018) — GH secretagogue pharmacology.
Metabolic Pathway
GLP-1 Signalling
Glucagon-like peptide-1 is released by intestinal L-cells after meals. It binds the GLP-1R, a Class B GPCR, on pancreatic β-cells where Gαs–cAMP–PKA signalling potentiates glucose-dependent insulin release. Central GLP-1R activation slows gastric emptying and reduces appetite. Native GLP-1 has a half-life of ~2 minutes, leading to the engineered long-acting analogues that now dominate the field.
Peer-reviewed references
- • Drucker DJ. Cell Metab (2018) — Mechanisms of action of GLP-1.
- • Müller TD et al. Mol Metab (2019) — Glucagon-like peptide 1.
Receptor Family
The Melanocortin System
Five melanocortin receptors (MC1R–MC5R) — all Class A GPCRs — integrate signals across pigmentation, adrenal cortisol output, energy balance, sexual arousal and exocrine function. Their endogenous ligands (α-, β-, γ-MSH and ACTH) derive from a single POMC precursor. Research peptides targeting MC3R/MC4R explore hypothalamic appetite circuits; MC1R/MC4R agonists are studied in pigmentation and arousal pathways respectively.
Peer-reviewed references
- • Cone RD. Endocr Rev (2006) — Studies on the physiological functions of the melanocortin system.
- • Krashes MJ et al. Trends Neurosci (2016) — Melanocortin-4 receptor signalling.
Immunology
Immune Pathways: Thymic & Host-Defence Peptides
Thymosin α-1 (Tα1) is a 28-residue immunomodulator that promotes T-cell maturation via TLR9 and influences dendritic cell function. Host-defence peptides such as LL-37 (cathelicidin) are amphipathic cationic peptides that disrupt microbial membranes while also modulating cytokine output. Research interest centres on chronic infection, sepsis and ageing.
Peer-reviewed references
- • Goldstein AL & Goldstein AL. Expert Opin Biol Ther (2009) — Thymosin α1.
- • Hancock REW et al. Nat Immunol (2016) — The immunology of host-defence peptides.
Cell Biology
Mitochondrial Biology & Derived Peptides
Mitochondria generate ATP via oxidative phosphorylation across the inner membrane. They also encode small open reading frames producing mitochondrial-derived peptides (MDPs) — MOTS-c, humanin, the SHLP series — which act as retrograde signals influencing insulin sensitivity, neuronal survival and metabolic homeostasis. SS-31 (elamipretide) binds cardiolipin to stabilise inner-membrane architecture.
Peer-reviewed references
- • Lee C et al. Cell Metab (2015) — MOTS-c, a mitochondrial-derived peptide.
- • Birk AV et al. J Am Soc Nephrol (2013) — SS-31 cardiolipin interaction.
Neurological Pathway
Neuroplasticity & BDNF Signalling
Brain-derived neurotrophic factor binds TrkB receptors to drive long-term potentiation, synaptogenesis and neuronal survival. Several research peptides — Semax (an ACTH 4–7 analogue) and Selank (a tuftsin analogue) — modulate BDNF and monoamine signalling and are widely studied for cognition and stress resilience.
Peer-reviewed references
- • Park H & Poo MM. Nat Rev Neurosci (2013) — Neurotrophin regulation of neural circuit development.
- • Levitskaya NG et al. Neurosci Behav Physiol (2008) — Pharmacological profile of Semax.
