Prolactin Actions on Casein and Lipid Biosynthesis in Mouse and Rabbit Mammary Gland Explants are Abolished by p-Bromphenacyl Bromide and Quinacrine, Phospholipase A₂Inhibitors

Abstract

p-Bromphenacyl bromide (BPB) at concentrations of 50 microM and above and quinacrine (50 microM) abolished the actions of prolactin (PRL) on casein and lipid biosynthesis in cultured mouse mammary gland explants. In cultured rabbit mammary gland explants, 100 microM BPB or quinacrine abolished the PRL stimulation of casein synthesis, while 50 microM BPB or 250 microM quinacrine abolished the PRL stimulation of lipid biosynthesis. Since BPB and quinacrine are known to inhibit the enzyme phospholipase A2 (PLA2), it is possible that ongoing PLA2 activity is essential for prolactin to express its actions on at least certain lactogenic processes.

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

“…Either acting alone or in concert with other hormones, prolactin has a plethora of effects on mammary epithelial function during lactation. Amongst other functions prolactin stimulates the production and/or secretion of casein, lipid [1], amino acids [2], and lactose [3] and activates ion transport processes such as those of sodium (Na + ), chloride (Cl − ), iodide (I − ), and calcium (Ca 2+ ) [4–6]. An increase in intracellular Ca 2+ ([Ca 2+ ] i ) in the mammary epithelium can serve two functions—it can contribute to the increased Ca 2+ 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.…”

Sequence of Prolactin Effects on Phospholipid Synthesis in Mouse Mammary Gland Explants

“…ODC activity is also stimulated by arachidonic acid, certain diglycerides, and the kinase C activators TPA and mezerein (Wing and Rillema 1983;Rillema 1985;Rillema and Waters 1986;Rillema and Whale 1988). In further studies it has been shown that phospholipase inhibitors including quinacrine and parabromphenacyl bromide abolish all the lactogenic effects of prolactin in mammary tissues in vitro ;Rillema 1979(b); Rillema, Etindi and Cameron 1986). More recently, it has been reported that PRL stimulates the formation of inositol bisphosphate (IP2) and inositol trisphosphate (IP3) 1-3 hours after PRL addition to cultured mouse mammary gland explants (Etindi and Rillema 1988).…”