A. Kauffman – Kisspeptin Signaling in Reproductive Biology (2013)

Автор: A. Kauffman
Название книги: Kisspeptin Signaling in Reproductive Biology
Формат: PDF
Жанр: Биологические науки
Страницы: 514
Качество: Изначально компьютерное, E-book

Kisspeptin has been shown to be both necessary and sufficient for activation of the reproductive axis, during puberty and later in adulthood. This makes kisspeptin a fundamental component of the reproductive axis. Kisspeptin has been deemed the single most potent stimulator of GnRH neurons yet known. The importance of kisspeptin has been documented in humans as well as non-human animal models, ranging from monkeys, sheep, and rodents to numerous fish species, thus signifying a highly conserved nature of its reproductive function. Importantly, kisspeptin neurons seem to mediate many of the regulatory effects of other signals, whether they are metabolic, circadian, hormonal, or stress. This places kisspeptin neurons in a unique position to be key nodal points and conduits for conveying numerous endogenous and exogenous signals to the reproductive axis.

We were lucky to get into the kisspeptin “ fi eld” during its early days, though we had
different avenues of entry. In early 2004, Sasha was a postdoctoral fellow in
Dr. Emilie Rissman’s lab in Virginia, where he was studying the effects of various
reproductive neuropeptides, such as GALP and GnRH variants, on sex behavior.
Dr. Rissman asked whether Sasha would be interested in studying sexual behavior
and sexual differentiation in a newly created transgenic mouse that was lacking an
orphan receptor called GPR54. This was just months after several high-pro fi le (and
soon-to-be seminal) papers had been published linking this receptor—and its ligand
kisspeptin—to reproductive status in humans and mice. The prospect of studying
this new, highly uncharacterized reproductive factor was too enticing to pass up.
Meanwhile, across the country in Seattle, Washington, Jeremy was also conducting
postdoctoral research in the lab of Dr. Robert Steiner, who had also recently
stumbled upon the exciting new kisspeptin system and was currently testing its
gonadotropin-releasing ability and sex steroid regulation in mice. Such was our
initial foray into kisspeptin reproductive biology, and our paths soon crossed when
Sasha headed west in 2005 to work in the Steiner lab. Since then, much has been
learned—by us and many others—about kisspeptin and GPR54. Satisfyingly, much
of what the fi eld has learned in the past decade has come from a growing community
of international scientists and labs situated all around the globe, not to mention
from a large variety of species and animal models. Indeed, kisspeptin has now been
shown, by numerous investigators, to be important for puberty and reproduction in
not only humans and mice, as originally demonstrated in 2003, but in a great assemblage
of vertebrate species, ranging from mammals of all shapes and sizes down to
frogs and fi sh.
As we rapidly approach the 10-year anniversary of the “discovery” of kisspeptin’s
role in reproductive biology, we believe this textbook is particularly timely.
The goal was to critically highlight—in a single cohesive volume—the functions
and regulation of kisspeptin as it relates to reproductive biology. To this end, we
present in-depth reviews of a wide range of kisspeptin topics, including (but not
limited to) hormone-releasing effects of kisspeptin in a variety of species (including
humans); consequences and underlying mechanisms of impaired kisspeptin systems; utility and bene fi ts of speci fi c kisspeptin experimental “tools” (including a variety
of new mouse models and novel chemical analogues); development of the kisspeptin
system; the role of kisspeptin in puberty; the regulation of kisspeptin circuits
by hormones, photoperiod, circadian signals, metabolic conditions, and stress, as
well as by other reproductive neuropeptides; alterations in kisspeptin induced by
endocrine-disrupting chemicals; and the newest kid on the block: electrophysiological
properties of kisspeptin neurons. In addition, this book emphasizes several larger
themes, including the importance and bene fi ts of comparative biology (despite—or
perhaps because of—the occasional “species differences”), as well as the value of
using both molecular and physiological analyses to advance the fi eld, not to mention
the growing importance of bedside-to-benchside (and back) research. Another
prominent message throughout the book is that there is still much to learn. While a
good deal of the “low-hanging fruit” on the kisspeptin experimental tree has now
been plucked, there are still many intriguing questions to be answered and many
fundamental gaps in our knowledge that demand fi lling. These numerous key areas
of future direction underscore the notion that, while we have come incredibly far in
the past decade, we still have a long way to go to solve some of reproductive biology’s
greatest puzzles. Thus, our aim for this book is to summarize and celebrate the
key fi ndings from the past decade of kisspeptin research, as well as stimulate both
future experimentation and further re fi nement of clinical use of kisspeptin for medical
and therapeutic endeavors.
In sum, we hope this cohesive and timely volume of kisspeptin reviews will be a
valuable educational and reference tool, useful for both the seasoned kisspeptin
researcher and clinician, as well as for new students and doctors wishing to dive into
the kisspeptin pool. We believe the comprehensive discussion herein of the numerous
kisspeptin topics will provide a fair, yet critical, assessment of the current state
of the kisspeptin fi eld, as well as identify key areas of targeted future research and
clinical applicability. Indeed, as we pass the fi rst 10-year marker on our kisspeptin
journey, it is likely that many of the open questions identi fi ed throughout this book
will guide the next series of exciting experimental and therapeutic kisspeptin ventures
well into the next decade.