Comparison
Gonadorelin vs. MOTS-c
Two peptides side-by-side — identity, evidence base, legal status and known adverse events.
Identity
Category
Research other
Research other
CAS no.
33515-09-2
1627580-64-6
Molecular weight
1182.29 g/mol
2174.61 g/mol
Half-life
0.1 h
no data
Sequence
pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-ArgMechanism of action
Gonadorelin
Gonadorelin acts as an agonist at the GnRH receptor on the gonadotroph cells of the pituitary and triggers release of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The temporal pattern of receptor exposure is decisive: pulsatile administration mimics the natural hypothalamic secretory rhythm and sustains LH/FSH release, whereas continuous exposure leads to receptor internalisation and desensitisation with subsequent paradoxical suppression of gonadotropins. The latter principle is exploited therapeutically by longer-acting GnRH agonists.
MOTS-c
MOTS-c arises from a short open reading frame located in the 12S rRNA region of the mitochondrial genome — unlike most peptides it is therefore not encoded by nuclear DNA. Mechanistically, preclinical work describes MOTS-c as modulating the folate cycle and the de novo purine biosynthesis tethered to it, thereby affecting the AMP/ATP ratio and, downstream, AMP-activated protein kinase (AMPK). Under metabolic stress, an AMPK-dependent translocation of the peptide into the cell nucleus and involvement in the regulation of stress-responsive genes (including via antioxidant-response-element-regulated transcription factors) have also been reported. These models derive predominantly from cell culture and rodents; the extent to which they reflect human physiology after administration of exogenous synthetic MOTS-c is not established by human studies.
Evidence base
Highest evidence
Human trial
Human trial
Studies
4
4
of which in humans
4
1
Effects recorded
4
4
Open conflicts
1
1
Documented adverse events
2
1
Legal status
Full entries
Frequently asked questions
- What is the difference between Gonadorelin and MOTS-c?
- Gonadorelin is classified as "Research other", while MOTS-c is classified as "Research other". Gonadorelin: Gonadorelin is the synthetic decapeptide with an amino-acid sequence identical to endogenous gonadotropin-releasing hormone (GnRH/LHRH). Historically approved in several countries for diagnostic testing of pituitary function and for fertility indications (pump systems). A defining feature is the opposite effect of pulsatile versus continuous administration: pulsatile stimulates, continuous leads to receptor desensitisation. MOTS-c: MOTS-c is a 16-amino-acid mitochondrial-encoded peptide (mitochondrial-derived peptide, MDP) whose open reading frame lies within the 12S rRNA region of mitochondrial DNA. In basic research (including the laboratories of Changhan Lee and Pinchas Cohen) it is described as a regulator of metabolic homeostasis and an activator of the AMPK pathway, and is sometimes discussed as an 'exercise mimetic'. The evidence comes almost entirely from cell and animal models; controlled human trials of MOTS-c as a therapeutic are lacking. It is not approved as a medicine anywhere and is traded on the grey market as a research chemical. This page contrasts both neutrally and source-based — with no usage or dosing recommendation.
- Which peptide is better supported by science, Gonadorelin or MOTS-c?
- The highest available evidence level is "Human trial" for Gonadorelin and "Human trial" for MOTS-c. A higher evidence level means more robust data, but says nothing about suitability for an individual. The full body of evidence is on each peptide's own page.
- What is the legal status of Gonadorelin and MOTS-c in Germany and the United States?
- Germany: Gonadorelin — Prescription, MOTS-c — Unapproved. United States: Gonadorelin — Prescription, MOTS-c — Unapproved. These are factual summaries with source and review date on the individual pages.