Kisspeptin as a functional probe
A response has a history. Reversal and pubertal transition make the diagnostic question especially demanding.
After reversal
The word reversal gives this study its force. In men with congenital idiopathic hypogonadotropic hypogonadism who had undergone reversal, the ability of an intravenous kisspeptin bolus to evoke an LH pulse tracked the presence of endogenous LH pulsatility. Endogenous means produced within the body. Acquiring kisspeptin responsiveness appeared to accompany reactivation of the reproductive axis.
Set beside the absent response in patients with abiding disease, this makes a functional challenge seem particularly worthwhile to me. A diagnostic name describes a disorder; a provoked response may add information about the activity of the network at the time it is tested. These were separate cohorts, so the comparison is a question to pursue rather than a direct experiment between the groups.
Detecting a change in capacity would make the challenge valuable to me. Raising LH alone seems a thinner achievement. A challenge becomes interesting when its answer helps describe the system receiving it.
Pubertal transition in boys
Healthy boys studied across the Tanner stages of puberty, alongside adult men, showed a significant LH rise after intravenous kisspeptin-10 only at Tanner stage V and in adults. A significant testosterone rise emerged from Tanner stage IV onward. The authors interpreted this as maturation of sensitivity during later puberty, reaching adult levels at Tanner stage V.
Those details make the capacity question more demanding. The same study located significant LH and testosterone responses at different stages. I want the hormone named precisely, alongside the developmental state of the person responding.
This study concerned healthy boys and adult men. Applying its stage-specific findings to a disorder would require a separate argument. The result gives an investigation of responsiveness a developmental context; it leaves the diagnostic usefulness of a challenge to be established in the population of interest.
At the neuron
A functional probe needs a biological explanation. In mouse experiments, kisspeptin failed to stimulate LH and FSH when Gpr54 was knocked out; the same paper reported GnRH release with a parallel serum LH rise after central kisspeptin administration in sheep. Those are animal findings, and they help locate the control point being challenged.
The mouse brain-slice work on GnRH neurons supplies a still closer view: kisspeptin depolarized the neurons and increased their firing through a phospholipase C/calcium-dependent pathway. It is satisfying to be able to move from a human challenge question down to the activity of a cell without pretending the experiments measured the same thing.
The amenorrhea studies complicate this further. A network’s reply can change during the experiment itself.
