Effects of Active Immunization against Somatostatin or Somatostatin Analogues on Male Rat Growth

Abstract

Effects of active immunization against somatostatin (SRIF) or various forms of somatostatin analogues on growth were investigated in male rats. In experiment 1, SRIF14, SRIF28, octreotide, Tyr 3 -octreotide or MK 608 were conjugated to human serum globulin and used as immunogens. Thirty-five Sprague-Dawley male rats were divided into seven groups and immunized against phosphate-buffered saline (PBS) (control 1), or one of the conjugated immunogens at five weeks of age. Booster immunizations were performed at 7, 9 and 12 weeks of age. Only SRIF14 induced the production of anti-somatostatin antibodies. There were no differences in blood GH concentration and growth performance between the SRIF14 group (with anti-SRIF antibodies) and other groups (without the antibodies). Although growth performance for the whole period was not affected by immunization with SRIF14 conjugate, daily weight gain and feed efficiency for 2 weeks after the third booster immunization were significantly improved, suggesting that the production of antibody against somatostatin can reach the minimal level for improving growth performance only after the third booster immunization in male rats. Experiment II was designed as a 2 2 2 2 2 factorial arrangement in which SRIF14 or Tyr11-SRIF14 was conjugated onto thyroglobulin or keyhole limpet haemocyanin (KLH) by glutaraldehyde or m-maleimidobenzoyl-N-hydroxysuccinimide coupling methods, and the immunization schedule was the same as experiment I. Anti-SRIF antibody titre values of the rats that received the conjugated SRIF14 or Tyr 11 -SRIF14 were higher than those injected with PBS. The levels of anti-SRIF antibody were not affected by the different coupling methods or by the different carrier proteins. In the Ag3 group treated with SRIF14 + KLH conjugate, total weight gain for the whole period and feed efficiency for 2 weeks after the third booster immunization were significantly different from other groups. Although GH concentration in blood was not changed by the production of antibody, our results show the possibility that active immunization against SRIF can improve growth performance in the male rat and SRIF14 peptide may be a potential candidate for active immunization.