Differential biological activities between mono- and bivalent fragments of anti-prolactin receptor antibodies.

Previous studies have established that antibodies against PRL receptors can mimic PRL effects on casein gene expression and on thymidine incorporation into DNA in the mammary gland. In the present work, bivalent F(ab')2 and monovalent Fab' fragments of the anti-PRL receptor antibodies were prepared. Both inhibited the binding of 125I-labeled PRL to rabbit mammary gland membranes.

Effect of sodium butyrate on the stimulation of casein gene expression by prolactin.

Sodium butyrate, but not isobutyrate, inhibits prolactin action on the induction of casein synthesis and casein mRNA accumulation in rabbit mammary explants. Sodium butyrate specifically prevents the generation of the prolactin relay which can be released from isolated membranes incubated with prolactin and which stimulates directly casein gene transcription when added to isolated mammary nuclei. This indicates that sodium butyrate exerts its inhibitory action essentially at the membrane level.

Effects of phorbol esters on multiplication and differentiation of mammary cells.

Three phorbol esters: phorbol-12,13-dibutyrate (PDB), 12-0-tetradecanoylphorbol-13-acetate (TPA) and phorbol-12,13-diacetate (PDA) were added at various concentrations (10(1)-10(4) ng/ml) to the culture medium of rabbit mammary explants. The three phorbol esters inhibited the mitogenic signals of insulin, EGF and prolactin. They also prevented the induction of casein synthesis and casein mRNA accumulation by prolactin.

[Comparison of the mechanism of action of insulin and prolactin].

One of the major actions of prolactin in the mammary cell is to activate the expression of casein genes by enhancing the transcription rate of the genes. Anti-prolactin receptor antibodies can mimic prolactin action when added to mammary cells, suggesting that a relay is formed at the membrane level and transferred to the target genes. None of the classical hormone intracellular relays can account for the transfer of the prolactin message.