Prolactin and Dexamethasone Regulate Second Messenger-Stimulated Cl− Secretion in Mammary Epithelia

Utchariya Anantamongkol,Jayashree Sarathy Nee Venkatasubramanian,Nateetip Krishnamra,Mrinalini C Rao,Mei Ao,Y Sangeeta Devi

doi:10.1155/2012/192142

Abstract

Mammary gland ion transport is essential for lactation and is regulated by prolactin and glucocorticoids. This study delineates the roles of prolactin receptors (PRLR) and long-term prolactin and dexamethasone (P-D)-mediation of [Ca2+]i and Cl− transport in HC-11 cells. P-D (24 h) suppressed ATP-induced [Ca2+]i. This may be due to decreased Ca2+ entry since P-D decreased transient receptor potential channel 3 (TRPC3) but not secretory pathway Ca2+-ATPase 2 (SPCA2) mRNA. ATP increased Cl− transport, measured by iodide (I−) efflux, in control and P-D-treated cells. P-D enhanced I− efflux response to cAMP secretagogues without altering Cl− channels or NKCC cotransporter expression. HC-11 cells contain only the long form of PRLR (PRLR-L). Since the short isoform, PRLR-S, is mammopoietic, we determined if transfecting PRLR-S (rs) altered PRLR-L-mediated Ca2+ and Cl− transport. Untreated rs cells showed an attenuated [Ca2+]i response to ATP with no further response to P-D, in contrast to vector-transfected (vtc) controls. P-D inhibited TRPC3 in rs and vtc cells but increased SPCA2 only in rs cells. As in wild-type, cAMP-stimulated Cl− transport, in P-D-treated vtc and rs cells. In summary, 24 h P-D acts via PRLR-L to attenuate ATP-induced [Ca2+]i and increase cAMP-activated Cl− transport. PRLR-S fine-tunes these responses underscoring its mammopoietic action.

Highlights

Prolactin is critical for the development of the mammary gland into a secretory type gland during lactation
By transfecting HC-11 with prolactin receptors (PRLR)-S we further examined if coexpression of both prolactin receptor long form (PRLR-L) and prolactin receptor short form (PRLR-S) isoforms altered the response to prolactin
We had previously demonstrated that short-term exposure to prolactin did not alter [Ca2+]i in HC-11 cells [24] but suppressed ATPdependent Ca2+ increases in MCF-7 cells [4]

Summary

Introduction

Prolactin is critical for the development of the mammary gland into a secretory type gland during lactation. An increase in intracellular Ca2+ ([Ca2+]i) in the mammary epithelium can serve two functions—it can contribute to the increased Ca2+ content of milk seen during lactation and it can serve as a signaling molecule to stimulate cell function, including fluid, that is, Cl− secretion, necessary for milk production. The present study attempts to delineate interplay between hormonal mediation of Ca2+ transporters and fluid secretion, in a single model system, the nontransformed mouse mammary epithelial cell line, HC-11. Most prominent are the long (PRLR-L) and short (PRLR-S) isoforms whose expression is both species and organ specific [9, 10]

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