Reproductive Experience Alters Prolactin Receptor Expression in Mammary and Hepatic Tissues in Female Rats1

Abstract

Recent studies have reported that reproductive experience in female rats alters prolactin (PRL) receptor gene expression in the brain as well as neural sensitivity to PRL. Given PRL's actions in nonneural tissues, that is, mammary tissue and liver, it was asked whether reproductive experience may also alter prolactin receptor (Prlr) gene expression in these tissues. Groups of age-matched female rats were generated with varying reproductive histories. Separate groups of primiparous (first lactation) and multiparous (second lactation) had mammary tissue and liver samples collected on Day 3 or 10 of lactation. A fifth group raised one litter to weaning and then resumed estrous cyclicity. This group and a final group of age-matched, virgin controls were killed on diestrus. Tissue was processed by quantitative PCR for expression rates of the long and short forms of Prlr mRNA as well as casein beta mRNA (mammary tissue only). Western blots were performed to quantify receptor protein content. Multiple lactations as well as lactation itself resulted in alterations in Prlr expression. Prlr gene expression in mammary tissue was increased in primiparous mothers compared with that in multiparous dams, whereas in the liver, Prlr expression was reduced during an initial lactation. In contrast, PRLR protein levels declined during lactation in mammary, but not hepatic, tissues. Overall, the results demonstrate that the prolactin receptor system is altered in nonneural tissues as a result of the female's reproductive history. The findings are discussed in the context of milk and bile production and PRL's possible role in breast cancer.

Long-term alterations in neural and endocrine processes induced by motherhood in mammals

“…PRLr gene expression increases in mammary tissue of primiparous versus age-matched, multiparous rats, a pattern opposite that found in neural tissues (Anderson et al, 2006). In contrast, in hepatic tissue PRLr gene expression was increased in primiparous mothers compared with that in multiparous dams (Bridges et al, 2011). These shifts in PRL receptor expression in mammary and hepatic tissues may reflect alterations in hormone sensitivity that enhance lactogenesis along with altered metabolic activity in multiparous dams.…”

“…In the rat increased expression of estrogen receptor β2 is found in mammary tissue as a function of prior parity (Kass et al, 2004). Likewise, the number of births affects expression of the long form of the PRL receptor gene in rat mammary tissue (Bridges et al, 2011). PRLr gene expression increases in mammary tissue of primiparous versus age-matched, multiparous rats, a pattern opposite that found in neural tissues (Anderson et al, 2006).…”

Prolactin prevents hepatocellular carcinoma by restricting innate immune activation of c-Myc in mice

“…In contrast, short-form PRLR (PRLR-S) does not meaningfully activate STAT5 or other PRLR-L pathways (10). In female reproductive tissues, the proportion of long: short-form receptor varies depending on hormonal fluctuations, whereas the liver maintains a constant preference for PRLR-S (11)(12)(13). In agreement with reports elsewhere (8), we found in mammary tissue and cells that 85-90% of total PRLR mRNA was PRLR-L, whereas in mouse and human liver tissue the vast majority was PRLR-S (Fig.…”

Physiological mechanisms, behavioral and psychological factors influencing the transfer of milk from mothers to their young

“…Consistent with its role in milk synthesis there is an increase in PRLR in the mammary gland of primiparous rats compared with non-lactating controls (Bridges et al, 2011). In rodents, the ability of exogenous prolactin administration to influence milk production decreases in late lactation while relative contribution of growth hormone increases (Flint et al, 1992;Hadsell et al, 2008).…”