Kisspeptin (KP)- and neurokinin B (NKB)- synthesizing neurons of the hypothalamic
arcuate nucleus play a pivotal role in the regulation of pulsatile gonadotropin-releasing
hormone (GnRH) secretion. Unlike in rodents and sheep, the homologous KP and NKB neurons
in the human infundibular region rarely express dynorphin- but often exhibit Substance
P (SP) immunoreactivity, indicating remarkable species differences in the neurochemical
phenotype of these neurons. In search for additional neuropeptides in human KP and
NKB neurons, we carried out immunofluorescent studies on hypothalamic sections obtained
from five postmenopausal women. Colocalization experiments provided evidence for the
presence of cocaine- and amphetamine-regulated transcript (CART) in 47.9+/-6.6% of
KP-immunoreactive (IR) and 30.0+/-4.9% of NKB-IR perikarya and in 17.0+/-2.3% of KP-IR
and 6.2+/-2.0% of NKB-IR axon varicosities. All three neuropeptides were present in
33.3+/-4.9% of KP-IR and 28.2+/-4.6% of NKB-IR somata, respectively, whereas triple-labeling
showed lower incidences in KP-IR (14.3+/-1.8%) and NKB-IR (5.9+/-2.0%) axon varicosities.
CART-IR KP and NKB neurons established contacts with other peptidergic cells, including
GnRH-IR neurons and also sent projections to the infundibular stalk. KP and NKB fibers
with CART often contained SP as well, while being distinct from CART fibers co-containing
the orexigenic peptide agouti-related protein. Presence of CART in human, but not
rodent, KP and NKB neurons represents a new example of species differences in the
neuropeptide repertoire of mediobasal hypothalamic KP and NKB neurons. Target cells,
receptor sites and physiological significance of CART in the efferent communication
of KP and NKB neurons in primates require clarification.
