Kisspeptin stimulates reproduction, and
kisspeptin cells in the arcuate nucleus (
ARC) express Ob-Rb in the mouse. Herein we report studies in ewes to determine whether
kisspeptin cells express Ob-Rb and respond to
leptin and whether reciprocal connections exist between
kisspeptin cells and
proopiomelanocortin (
POMC) or
neuropeptide Y (NPY) cells to modulate reproduction and metabolic function. Kiss1
mRNA was measured by in situ hybridization in ovariectomized ewes that were normal body weight, lean, or lean with
leptin treatment by intracerebroventricular (icv) infusion (4 microg/h, 3 d). Kiss1 expression in the
ARC and the preoptic area was lower in hypogonadotropic lean animals than animals of normal weight, and icv infusion of
leptin partially restored Kiss1 expression in lean animals. Single-cell
laser capture microdissection coupled with real-time PCR showed that Kiss1 cells in the preoptic area and
ARC express Ob-Rb. Double-label fluorescent immunohistochemistry showed that reciprocal connections exist between
kisspeptin cells and NPY and
POMC cells. Accordingly, we treated ovariectomized ewes with
kisspeptin (5 microg/h, icv) or vehicle for 20 h and examined
POMC and NPY gene expression by in situ hybridization.
Kisspeptin treatment reduced
POMC and increased NPY gene expression. Thus,
kisspeptin neurons respond to
leptin and expression of Kiss1
mRNA is affected by
leptin status.
Kisspeptin cells communicate with NPY and
POMC cells, altering expression of the relevant genes in the target cells; reciprocal connections also exist. This network between the three cell types could coordinate brain control of reproduction and metabolic homeostatic systems.