Effects of Kisspeptin on Hormone Secretion in Humans - Kisspeptin Signaling in Reproductive Biology - page 105

Conclusions
Studies of the effects of kisspeptin in human subjects have not only validated
fi ndings made in animal models, they have also contributed new insights into the
intricate physiology of kisspeptin. Some of these key insights include the fi ndings
that brief exposure to kisspeptin results in sustained GnRH release in vivo, that
kisspeptin resets the GnRH pulse generator in men, that kisspeptin secretion and
GnRH responsiveness to kisspeptin vary across the menstrual cycle, and that desen-
sitization occurs after days of exposure to kisspeptin. The pulsatile pattern of endog-
enous kisspeptin secretion [ 64 , 65 ] suggests that modes of kisspeptin administration
that result in brief pulses of kisspeptin in the blood are more likely to refl ect the
normal physiological effects of kisspeptin. Future studies using short-acting boluses
of kisspeptin may elucidate the precise effects of sex steroids on the response to
exogenous kisspeptin and may thereby result in a better understanding of how
changes in both kisspeptin secretory tone and GnRH neuronal responsiveness to
kisspeptin contribute to the physiological variation in neuroendocrine activity
across the menstrual cycle and across the life cycle. In contrast, protocols that result
in prolonged kisspeptin exposure open the door for pharmacologic manipulation of
the kisspeptin signaling pathway, and it will be important to determine the precise
conditions under which continuous kisspeptin administration can bring about
desensitization of the kisspeptin receptor in humans. Importantly, kisspeptin is just
starting to be used to probe the pathophysiology of reproductive disorders such as
isolated GnRH defi ciency, and the excellent safety record for kisspeptin to date
opens the door for future studies using kisspeptin as a diagnostic and therapeutic
tool for the care of patients with these disorders.
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