Expression of Calcitonin Receptor in Rat Mammary Gland during Lactation

Abstract

Abstract. 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.

Calcitonin receptor immunoreactivity associated with specific cell types in diseased radial and internal mammary arteries

“…Alternatively, it has been demonstrated that particular isoforms of CTR, when expressed by transfected cell lines, slow down the cell cycle 28,29 . This inhibition of cell proliferation may be an important control mechanism for the ordered process of healing, in which the drive is a return to the original state or control of organogenesis as demonstrated in the developing (discussed above) or lactating breast 30 . An integrated model might include the expression of CT‐like ligands in damaged or diseased tissues, including CVD, where they act both as a molecular beacon (with a tropic factor 27 ) for the recruitment of CTR+ precursor cells and as a mechanism to restrict cell division that may be important for the control of the healing process.…”

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

“…Calcitonin acts on the calcitonin receptor, which is expressed by osteoclasts (660), lactating mammary epithelial cells (432,938), and pituitary (831), as well as numerous other tissues during embryonic and fetal development (437). Pharmacological doses of CGRP and amylin can activate the CTR, but at physiological doses they act on different receptors (787).…”

The calcitonin receptor regulates osteocyte lacunae acidity during lactation in mice

“…Whilst it is well established that circulating levels of calcitonin are elevated during lactation in both humans and mice due to extrathyroidal production (Stevenson et al 1979, Gonen et al 2005 and the expression of the CTR gene is upregulated in mammary tissue during lacation in mice (Tverberg et al 2000, Ishii et al 2006, the expression of the CTR within bone during pregnancy and lactation has not been documented. We now show that the CTR within bone is markedly increased at the end of pregnancy and lactation in control mice and is restored to virgin control levels by 3 weeks post-lactation.…”

“…A number of questions relating to the physiological role of the CTR to protect the maternal skeleton during lactation, however, remain unanswered. While it is established that the circulating levels of calcitonin (Toverud et al 1978, Bucht et al 1986, Miller 2006) and the expression of the CTR gene in mammary tissue (Ishii et al 2006) are increased in lactation, very little is known about the level of CTR gene expression within bone during pregnancy and lactation. Second, the mechanism by which the CTR inhibits osteocytic osteolysis during lactation has not yet been identified and, lastly, it is not known whether the CTR is required for the restoration of the bone mineral to the osteocyte lacunae post-lactation.…”