Effects of Phospholipases on Ornithine Decarboxylase Activity in Mammary Gland Explants from Midpregnant Mice*

Abstract

Phospholipases A2 (PLA2) and C (PLC) stimulate ornithine decarboxylase (ODC) activity in mouse mammary gland explants preincubated with insulin and cortisol. PLC concentrations of 0.1 micrograms/ml produced responses that were close in magnitude to that of PRL, whereas PLA2 at concentrations of 5-50 micrograms/ml was 35-40% as efficacious as 1 microgram/ml PRL in stimulating ODC activity. The time courses of PLC, PLA2, and PRL actions on ODC activity were not different from one another. When PRL and PLC were tested together, a response greater than the sum of the responses of each of these agents alone was observed; PLA2 (25 micrograms/ml) when tested with PRL produced a nonadditive response. The action of PRL on ODC activity was significantly attenuated by quinacrine, an inhibitor of PLC and PLA2 activities. These results suggest that PRL, PLA2, and PLC stimulate ODC activity via similar mechanisms in the mammary gland and make tenable the idea that the action of PRL on ODC activity may be carried out via an action of PRL on PL activity.

Prolactin involvement in breast cancer.

“…The phosphorylation and activation of phosphatidylinositol-3 (PI3)-kinase for signal transduction of PRL in Nb2 cells have been reported (Alsakkaf et al 1996). Endogenously added phospholipase C, an enzyme that hydrolyzes L-α-phosphoinositol 4,5-diphosphate (PIP2) to D-myo-inositol triphosphate (IP3) and diacylglycerol, elicited PRL-like effects on ornithine decarboxylase activity and RNA synthesis in pregnant mouse mammary gland explants in culture (Rillema et al 1983). In NOG-8 mammary cells, PRL activates and translocates PKC to the membranes within 5-10 min (Banerjee & Vonderhaar 1992).…”

Prolactin‐Stimulated Mitogenesis of Cultured Astrocytes Is Mediated by a Protein Kinase C‐Dependent Mechanism

“…Protein kinase C (PKC) has been implicated as one of the transmembrane signaling systems involved in the regulation of PRL-induced cell proliferation. In Nb2 lymphoma cells, a cell line which is dependent on lactogenic hormones for proliferation (Gout et al, 1980;Tanaka et al, 1980), studies have suggested that PKC may be involved in the PRL-induced mitogenesis in this cell line (Rillema et al, 1983(Rillema et al, , 1989Buckley et al, 1986). Similarly, in the rat liver, the trophic effects of PRL have been linked to an increase in 1,2-diacylglycerol and the subsequent activation of PKC (Buckley and Buckley,199 1).…”

“…Stimulation of brain tissue in vivo and in vitro with physiological concentrations of PRL has been shown to result in the rapid translocation of PKC from the cytosol to the membrane (DeVito et al, 199 1). Because PKC has been implicated in the regulation of the mitogenic effect of PRL in several tissues (Rillema et al, 1983(Rillema et al, , 1989Buckley et al, 1986;Buckley and Buckley, 199 l), we examined the possibility that PKC may mediate the mitogenic effect of PRL in cultured astroc ytes.…”

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

“…In subsequent studies, we observed that exogenously added PLA 2 would also stimulate the rate of [ 3 H]-leucine incorporation into a casein-rich phosphoprotein fraction in cultured mouse mammary tissues; PLA 2 was only efficacious, however, if the tissues were also exposed to 0.5 raM spermidine, added to the cultured medium (Rillema, Linebaugh and Mulder 1977). More recently, we have shown that PLA 2 will stimulate ornithine decarboxylase activity in cultured mouse mammary tissues, but the magnitude of a maximal stimulatory concentration of PLA 2 is only a fraction of that elicited with prolactin (Rillema, Wing and Foley 1983). The prolactin and PLA 2 effects on ODC activity are, however, nonadditive when maximum stimulatory concentrations of these agents are tested together.…”