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The hypothalamic-pituitary-gonadal (HPG) axis is a textbook example of cascading peptide signaling, and several research compounds act at one of its levels.
Kisspeptin
Hypothalamic neurons release kisspeptin, which activates KISS1R on GnRH neurons. It is the «switch» that initiates puberty and regulates the axis's pulsatility.
GnRH
A decapeptide released in pulses toward the pituitary. Pulse frequency favors LH (fast pulses) or FSH (slow pulses).
LH and FSH
Pituitary glycoproteins that act on the gonad: LH on sex steroid production, FSH on gamete maturation.
Feedback
Testosterone, estradiol, progesterone and inhibin restrain the axis at the hypothalamus and pituitary.
Compounds that act at each level
| Level | Compound | What it mimics or modulates |
|---|---|---|
| Hypothalamus | Kisspeptin | Stimulates GnRH release |
| Pituitary | GnRH analogs | Stimulation in pulses or suppression with continuous exposure |
| Gonad | hCG | LH-type activity (shares the LH/CG receptor) |
| Gonad | hMG (menotropin) | FSH + LH activity |
Why the level matters
A compound that acts high in the axis (kisspeptin) preserves the body's own feedback and pulsatility; one that acts low (hCG) stimulates the gonad directly and, over time, the negative feedback of the steroid produced can suppress endogenous LH and FSH secretion. It is the same principle that distinguishes a GH secretagogue from exogenous GH.
Oxytocin, in the same neighborhood
Oxytocin is a hypothalamic nonapeptide released by the posterior pituitary. Besides its role in childbirth and lactation, its central action on social behavior has motivated an extensive intranasal literature, with heterogeneous results and effects that depend greatly on context and the individual.
In any endocrine axis, the lower a compound acts, the more direct its effect and the more likely it is to suppress the body's own production through feedback.
Catalogue compounds mentioned in this lesson
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