Ovine placental lactogen is a potent somatogen in the growth hormone (GH)-deficient rat: comparison of somatogenic activity with bovine GH.
The somatogenic effects of recombinant ovine placental lactogen (oPL) were investigated in the GH-deficient dwarf rat and compared to those of identical doses of recombinant bovine GH (bGH) in three independent studies. Both oPL and bGH treatments resulted in an increase (P less than 0.05) in body weight gain compared to that in saline controls, with oPL treatment being more potent than bGH (P less than 0.05). In promoting linear growth, oPL was more potent (P less than 0.05) than bGH in some instances. The nitrogen content of dry carcass matter was increased with oPL treatment compared to saline (P less than 0.05), with a nonsignificant increase in bGH-treated animals. Carcass fat was similarly reduced by both oPL and bGH treatment (P less than 0.05) compared to saline. Serum insulin-like growth factor-I (IGF-I) concentrations were increased significantly (P less than 0.05) by both oPL and bGH treatments, with a significantly greater effect of oPL suggested in one study. No increase in hepatic IGF-I mRNA was evident with either treatment, suggesting that the increase in serum IGF-I is due to posttranscriptional mechanisms. The expression of IGF-binding protein-3 hepatic mRNA was increased (P less than 0.05) with bGH treatment compared to that after saline treatment, but was unaffected by oPL treatment, indicating regulation by GH at the transcriptional level. The binding of [125I]bGH to hepatic membrane preparations demonstrated no difference in specific binding compared to that in saline controls. However, [125I]oPL specific binding was greater in oPL-treated animals (P less than 0.05). Animals treated with bGH had reduced (P less than 0.05) hepatic GH receptor mRNA compared to saline controls, but oPL treatment had no effect. Thus, oPL is a potent anabolic and lipolytic agent in the dwarf rat, exerting greater somatogenic effects on some parameters than bGH. Our data suggest differences in receptor binding and effects on GH receptor and IGF-binding protein-3 expression with these two treatments, raising the possibility of actions through different pathways or differential effects at the GH receptor level.
Singh
K
K
Department of Pediatrics, University of Auckland, New Zealand.
Ambler
G R
GR
Breier
B H
BH
Klempt
M
M
Gluckman
P D
PD
D000704:Analysis of Variance; D000818:Animals; D001824:Body Constitution; D002417:Cattle; D015342:DNA Probes; D004392:Dwarfism / Q000235:genetics / Q000503:physiopathology*; D006128:Growth / Q000187:drug effects*; D013006:Growth Hormone / Q000172:deficiency* / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010928:Placental Lactogen / Q000494:pharmacology*; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D012756:Sheep; D015430:Weight Gain / Q000187:drug effects
D015342:DNA Probes; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D011061:Poly A; D012313:RNA; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D010928:Placental Lactogen