Kisspeptin cells in the ewe brain respond to leptin and communicate with neuropeptide Y and proopiomelanocortin cells.
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.
Backholer
Kathryn
K
Department of Physiology, Monash University, Clayton, Victoria 3800, Australia.
Smith
Jeremy T
JT
Rao
Alix
A
Pereira
Alda
A
Iqbal
Javed
J
Ogawa
Satoshi
S
Li
Qun
Q
Clarke
Iain J
IJ
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D008954:Models, Biological; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D010052:Ovariectomy; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
D020738:Leptin; D009478:Neuropeptide Y; D054411:Receptors, Leptin; D025521:Tumor Suppressor Proteins; D011333:Pro-Opiomelanocortin