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

• Published in: Journal of Signal Transduction Vol. 2012; no. 2012; pp. 81 - 95
• Main Authors: Sarathy nee Venkatasubramanian, Jayashree, Anantamongkol, Utchariya, Rao, Mrinalini C., Krishnamra, Nateetip, Devi, Y. Sangeeta, Ao, Mei
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Limiteds 01.01.2012; Hindawi Puplishing Corporation; Hindawi Publishing Corporation; Hindawi Limited
• Subjects: Crystal structure; Kinases; Lactose; Milk; Proteins; Rodents; Studies
• ISSN: 2090-1739; 2090-1747
• DOI: 10.1155/2012/192142

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.