The neuropeptide galanin augments lobuloalveolar development.
Mammary lobuloalveolar development during pregnancy is controlled by ovarian sex steroids and pituitary prolactin release. In organ culture these hormones are incapable of reproducing the density and size of lobuloalveoli seen in mice, suggesting the existence of other undiscovered factors. We showed previously that galanin knockout mice fail to lactate sufficiently for pup survival following their first pregnancy. Here we demonstrate that prolactin treatment of galanin knockout mice allows pup survival but does not completely rescue lobuloalveolar development or reduced milk protein expression. When galanin was used in combination with prolactin in mammary organ culture, larger and more numerous lobules were produced than with prolactin alone. Galanin alone produced sustained activation of STAT5a and the induction of milk protein expression but did not induce lobulogenesis. Examination of the transcriptional interaction between galanin and prolactin using oligonucleotide microarrays demonstrated synergistic and antagonistic modes of interaction between these hormones. These data establish a new role for galanin as a hormone augmenting mammary development during pregnancy in concert with prolactin.
Naylor
Matthew J
MJ
Development Group, Cancer Research Program and Neurobiology Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, New South Wales 2010, Australia.
Ginsburg
Erika
E
Iismaa
Tiina P
TP
Vonderhaar
Barbara K
BK
Wynick
David
D
Ormandy
Christopher J
CJ
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D004347:Drug Interactions; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D019004:Galanin / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007774:Lactation; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000254:growth & development* / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008894:Milk Proteins / Q000032:analysis / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D011247:Pregnancy; D011388:Prolactin / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; D015534:Trans-Activators; D019004:Galanin; D011388:Prolactin