Expression of calcitonin receptor in rat mammary gland during lactation.
Calcitonin (CT) and calcitonin receptor (CTR) have been reported to play an important role in mammary tissue during pregnancy, lactation, and involution. In the present study, the expression and distribution of CTR mRNA in rat mammary tissue during pregnancy and lactation were investigated. As measured by real-time RT-PCR, CTR mRNA levels were increased only slightly during pregnancy, but increased markedly immediately postpartum and remained elevated through lactation, with the highest levels observed 14 days postpartum. In situ hybridization analysis showed that intense CTR mRNA signals were detected in the whole mammary gland. We performed immunohistochemistry to determine distribution of CTR in the mammary epithelium. CTR has been reported to act as an amylin receptor when heterodimerized with receptor activity modifying protein-1 (RAMP1) or RAMP3. mRNA expression of RAMP1 and RAMP3 in mammary tissue decreased during pregnancy and lactation, and amylin mRNA was undetectable, suggesting that up-regulated CTR in lactating mammary tissues binds CT rather than amylin. In primary cultures of mammary cells isolated from rat dams 14 days postpartum, CT produced a statistically significant decrease in thymidine incorporation. These results suggest that up-regulation of CTR during lactation may contribute to inhibition of mammary epithelial cell proliferation.
Ishii
Aiko
A
Department of Pathology, Wakayama Medical University, Wakayama, Japan.
Nakamura
Misa
M
Nakamura
Atsushi
A
Takeda
Koichi
K
Han
Bo
B
Kakudo
Kennichi
K
D000818:Animals; D002116:Calcitonin / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007774:Lactation / Q000378:metabolism*; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011920:Rats, Inbred WF; D058262:Receptor Activity-Modifying Protein 1; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014886:Weaning
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C545508:Ramp1 protein, rat; C545510:Ramp3 protein, rat; D058262:Receptor Activity-Modifying Protein 1; D058264:Receptor Activity-Modifying Protein 3; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin; D002116:Calcitonin; D004247:DNA