Prolactin-like activity of anti-prolactin receptor antibodies on casein and DNA synthesis in the mammary gland.
Prolactin receptors were partially purified from rabbit mammary gland membranes by using an affinity chromatography technique. Antibodies against this prolactin receptor preparation were obtained in guinea pig and sheep. Both antisera were able to inhibit the binding of 125I-labeled ovine prolactin to rabbit mammary gland membranes. When added to culture media of rabbit mammary explants, the anti-prolactin receptor antiserum inhibited the capacity of prolactin to initiate casein synthesis and casein mRNA accumulation as a function of the antiserum concentration. However, in the absence of prolactin, both antisera (guinea pig and sheep) at moderate concentrations were capable of mimicking prolactin action on casein gene expression and on DNA synthesis. At higher concentrations, the anti-prolactin receptor antibodies inhibited their own actions. Several characteristics of the prolactin effect were also observed with the anti-prolactin receptor antibody: the stimulatory effect of the antibody was amplified by glucocorticoids; colchicine, which was capable of blocking prolactin action, also prevented the induction by the antibody. Lysosomotropic agents, which do not interfere with prolactin action, did not alter the response observed with the antibody. These results indicate that an anti-prolactin receptor antibody can mimic two major actions of prolactin obtained in mammary explant culture and suggests that the prolactin molecule is not required beyond the initial binding to its receptor.
D000818:Animals; D000937:Antigen-Antibody Reactions; D001667:Binding, Competitive; D002364:Caseins / Q000096:biosynthesis* / Q000235:genetics; D003078:Colchicine / Q000494:pharmacology; D005260:Female; D008321:Mammary Glands, Animal / Q000502:physiology*; D008566:Membranes / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000302:isolation & purification; D011981:Receptors, Prolactin
D002364:Caseins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011981:Receptors, Prolactin; D011388:Prolactin; D003078:Colchicine