Hypothalamus Anterior pituitary [Effects on skeletal homeostasis: Invitro ~ KISS1/KISSIR expressed in osteoblast and osteoclast lineage cell ines. Kisspeptin | = Positive stimulates osteoblast precursor differentiation in mause mesenchymal stem cells, | Sam Negative Invivo ~ Mediates @ nouroskeletal circuit in the ARC modulating bone formation in mice No effect or uncertain Invitro ~ GnéH and GnRHR expressed in canine osteosarcoma cell ines and fo lesser extent in normal canine osteogenic progenitor cells. Peripheral GnRH signaling may participate direct in bone ‘emodelig in osteosarcom cll ines, potentially through RANKL and the serotonergic system. | Invivo~ Wo data ‘In vitro — Oseobiasts (out oot esteoclasts) express PALR. PAL acts drectly on bone to predominantly increase bone resoration (via osteoblast-osteactast pathways). {In vivo ~ Stinulats intestinal calcium absorption uring pregnancy and lactation, as well as direct and independent negative effects on bone remodeling, Invitro — FSHR expressed in human ostoclasts and mesenchymal stem cells (but not in mature osteoblasts}, with data supporting a dvec ole in osteclastogenesis, Invivo— Several fot 0 al) non-humen experimental and human observational studies suggest negative ‘bone effects, However, as yet no interventional human studies identifying direct bone effects, in fro ~ Lif expressea on primary nunan osteoblasts ard osteobiastike cel nes. In vivo Etec on bone physiology predaminanty mediated vie gonadal sex steroids (ndiect / @o> \ ‘ ww {In vitro PR expressed on osteoblasts and osteoclasts, with stimulatory effects on osteoblasts. In vivo ~ Promotes bane formation in cotaboration with estogen (but potentialy detrimental at b Pa, gas “Bstosterone Esirogen’ ‘supraphysiogical doses {In vitro Receptor expressed by osteoclasts stimulating osteaclastogenesis. Positive effect on astenblastogenesis {In vivo Positive effects on bone remodelng. Disrupted relaxin pathways reduces bone density {In vitro ~ Stimulates ostoblastogenesis ard osteoclastogenesis in primary murine bone marrow culture, but sunpresses mineralization in human osteoblast preparation, ‘In vivo ~ Stimulatory elects on bone formation ‘In vitro ~ Suppresses osteoblastogenesis and osteoclastogenesis in bath primary murine bone marrow culture and human mesenchymal cells, {In-vivo Positive effects on bane formation in mice. Associaton with bone mass and turnover (inverse) in humans,