AGE-RELATED EFFECTS OF ECTOPIC PITUITARY TRANSPLANTS ON THE ACTIVATION OF AMES DWARF MOUSE LYMPHOCYTES IN-VITRO

Prolactin (PRL), one of the anterior pituitary hormones, has been impl icated in the development and maintenance of immune system function, T he following experiments were conducted to evaluate age-related effect s of PRL on immune system activity in a PRL-deficient mouse model, the Ames dwarf, Two- and ten-month-old dwarf and phenotypically normal ma le mice were used. Six dwarf mice from each age group received a surgi cally implanted pituitary (under the kidney capsule) from a normal don or female mouse, Six different dwarfs were similarly operated but had no pituitary graft inserted and will be referred to as sham-operated d warfs. Three weeks following surgery, spleens were removed from the dw arfs and age-matched normal mice and splenocytes isolated, The two age groups will subsequently be referred to as ''3-month-old'' and ''11-m onth-old'', respectively. The splenocytes were used in mitogen-induced (concanavalin A [Con A]; phytohemagglutinin [PHA]; lipopolysaccharide [LPS]) proliferation assays, and histopaque isolated lymphocytes were used for T cell surface marker determination. Pituitary grafting incr eased body weights of dwarf mice although the weights were less than c ontrol mice independent of age. A similar pattern was observed for tot al number of splenocytes per spleen. In young animals, the relative nu mber of splenocytes per gram of body weight increased in pituitary gra fted dwarfs reaching values of control mice, whereas much smaller diff erences were observed in older animals. The relative percentage of CD4 + cells was reduced (P < 0.01) in 9-month-old pituitary-grafted mice, compared with sham-operated dwarf mice, while no differences were obse rved between sham-operated dwarf and normal mice. Pituitary grafting d id not affect the numbers of CD8+ cells, In 11-month-old animals, the relative percentages of CD4+ and CD8+ cells were greater (P < 0.05) in , sham-operated dwarf than in normal mice but not affected by pituitar y grafting. At 3 months of age, proliferation of splenocytes in respon se to Con A was increased (P < 0.05) in sham-operated dwarfs and reduc ed (P < 0.05) in pituitary-grafted dwarfs compared with normal mice. i n contrast, PHA stimulation of splenocytes was decreased (P < 0.05) in sham-operated compared with normal, and was still tower in mice recei ving an ectopic pituitary, Substantially different responses were obta ined in 11-month-old animals, In response to Con A, splenocytes from s ham-operated dwarfs exhibited a reduced IP < 0.05) proliferative capac ity as compared with normals, and proliferation was increased in pitui tary-grafted as compared with sham-operated dwarfs. In the presence of PHA, the proliferative capacity of splenocytes was greater (P < 0.05) in sham-operated dwarfs as compared to normals and pituitary grafting normalized this parameter, These results demonstrate differential eff ects of PRL deficiency (sham-operated dwarfs versus normal) and of PRL replacement (pituitary-grafted versus sham-operated) in young as comp ared with old dwarf mice on immune system activation.