Comparison of the galactopoietic response to pituitary-derived and recombinant-derived variants of bovine growth hormone

Two studies were designed to examine the differences in galactopoietic potency of molecular variants of pituitary- and recombinant-derived bovine GH (bGH). The recombinant bGH molecules included amino-terminal and position-127 amino acid substitutions which are representative of two of the four natural pituitary variants or of partially degraded bGH molecules. Amino-terminal variants of bGH included methionine (Met¹), alanine (Ala¹), serine (Ser¹) or deletion of four amino acids (Δ^1-4). The Δ^1-4 variants were representative of degradation products previously isolated in pituitary bGH preparations. In the first study, 54 lactating Holstein cows received i.m. injections of a buffer solution (control), pituitary-derived bGH, or recombinant-derived [Met¹,Leu¹²⁷]-bGH, [Met¹,Val¹²⁷]-bGH, [Ala¹,Leu¹²⁷]-bGH, or [Ala¹,Val¹²⁷]-bGH. Cows received 25 mg bGH/day for 21 days. Substitution of the amino-terminal alanyl residue with methionine did not affect milk response. GH variants with Val¹²⁷ elicited a greater milk response (8.5 kg/day) than Leu¹²⁷ bGH variants (6.5 kg/day). The average milk response to the four recombinant bGH variants was 7.5 kg/day greater than controls compared with 4.4 kg/day for pituitary-derived bGH. In contrast, blood bGH concentrations were equivalent for pituitary and recombinant bGH treatments, approximately 20 μg/l more than control levels at 3 h after injection. Blood free fatty acid concentrations were increased, but insulin and glucose levels were unaffected by bGH treatment. In the second study, 54 lactating Holstein cows received i.m. injections of a buffer control solution or recombinant-derived [Met¹,Leu¹²⁷]-bGH, [Ser¹,Leu¹²⁷]-bGH, [Ser¹,Val¹²⁷]-bGH, [Δ^1-4,Leu¹²⁷]-bGH or [Δ^1-4,Val¹²⁷]-bGH. Cows received 25 mg bGH/day for 28 days. The milk response to full-length bGH variants was 6.6 kg/day greater than the response to the amino-terminal deletion variants (P < 0.05). Substitution of valine for leucine did not affect milk response to either the deletion (Δ^1-4) or full-length (Met¹ or Ser¹) bGH molecules. In conclusion, the lowered galactopoietic potency of pituitary bGH preparations was demonstrated, at least in part, to be due to the presence of amino-terminal amino acid deletions rather than differences in amino acid sequences of recombinant bGH. Ala¹ bGH variants with valine at position 127 elicited a greater milk response than Leu¹²⁷ variants.