Induction of Lactogenic Binding Sites in the Liver of the Snell Dwarf Mouse

Abstract
Lactogenic binding sites were shown to be absent in the livers of Snell dwarf mice (dw/dw). Phenotypically normal littermates (DW/?), bound o[ovine]PRL [prolactin] with an apparent affinity constant, Ka, 15 .times. 109 M-1 and possessed quantities of binding sites equivalent to 25 and 8 fmol [femtomoles]/mg liver protein in females and males, respectively. Lactogenic binding sites were induced in livers of dw/dw mice upon transplantation of intact DW/? pituitaries under the kidney capsule, induction occurring in a biphasic manner. Detectable binding sites could not be reinduced by daily single oPRL injections into dw/dw after the transplanted pituitary had been excised. I.p. injections of b[bovine]GH [growth hormone] + oPRL + thyroxine (T4) every 4 or 8 h induced detectable binding sites that were maximally detectable 8-12 h after the final injection. Injection of bGH alone every 8 h for 2 days also induced the lactogenic binding sites in an amount approaching that of the female DW? DW/? males exhibited a 6.5-fold or 2-fold increase in the number of lactogenic binding sites when treated every 4 h with bGH or oPRL, respectively. Addition of oPRL + T4 to the bGH injections lowered the increase to 2-fold. [125I]bGH did not bind nor did bGH compete with [125I]-oPRL bound to the membrane preparations. The inability of bGH to bind to the membrane preparations suggests either the necessity of an intermediate bGH-responsive tissue for induction of the lactogenic receptor or the presence of a bGH binding site in the liver, undetectable by receptor assays currently in use. The Snell dwarf mouse provides a convenient and naturally occurring model system to study the induction of lactogenic binding sites.