Receptor activator of nuclear factor kappa B ligand (RANKL): another link between breast and bone.
Mice rendered null for the genes encoding receptor activator of nuclear factor kappa B ligand (RANKL) or its receptor, RANK, are osteopetrotic because of failure of osteoclast development. The failure of lactation owing to the lack of development of lobulo-alveolar structures during pregnancy, despite earlier stages of mammary gland development being normal, is now added to each of these phenotypes. The breast phenotype in RANKL-/- (but not in RANK-/-) mice is rescued by treatment of pregnant mice with RANKL, indicating a key role for these tumour necrosis factor (TNF) ligand and receptor family members in a crucial terminal step in breast development and lactation. Both RANKL and RANK are synthesized by mammary epithelial cells, with both prolactin and parathyroid hormone-related protein (PTHrP) able to enhance production of mRNA for RANKL. These findings reveal a paracrine-autocrine system in lactation control, with novel signalling pathways that reflect intercellular communication processes in bone.
Martin
T J
TJ
St Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy 3065, Victoria, Australia. j.martin@medicine.unimelb.edu.au
Gillespie
M T
MT
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D001940:Breast / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D044162:Parathyroid Hormone-Related Protein; D011247:Pregnancy; D011506:Proteins / Q000235:genetics / Q000502:physiology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse