Negative Cooperativity in the Prolactin-Receptor Interaction in the Rabbit Mammary Gland: Action of High Prolactin Concentration

¹ Department of Animal Breeding, Faculty of Agriculture, University of Tokyo, Bunkyo-ku, Tokyo, Japan

The concentration of serum prolactin in the lactating mother is elevated by milking, and the dissociation of prolactin from the receptor is accelerated by the presence of prolactin in vitro. The interaction of prolactin at high concentrations with the receptor was examined using lactating rabbit mammary microsomes. At low concentrations of prolactin, the Scatchard plots were linear. At concentrations >30 ng/ml, however, the slope of the Scatchard plot line changed. The Hill coefficient decreased from 1.09 to .77 or from .80 to .65 as prolactin concentrations increased. When a receptor preloaded with prolactin was utilized, prolactin at concentrations >20 ng/ml associated with the receptor in a concentration-dependent manner. The Hill coefficient of this reaction was .70. The receptor remained intact for reassociation after prolactin-induced dissociation. These data indicate that, because of the presence of negative cooperativity, prolactin at exceedingly high concentrations greatly accelerates the prolactin-binding reaction. The elevation of serum prolactin induced by milking may be important in the maintenance of active milk synthesis.

Key Words: prolactin • mammary prolactin receptor • negative cooperativity • prolactin-induced association and dissociation

Submitted on May 18, 1993
Accepted on October 7, 1993