title: Use of osmotic pumps for subcutaneous infusion of growth hormone-releasing factors in steers and wethers.
abstract: Osmotic pumps were evaluated for 7-d delivery of growth hormone-releasing factor (GRF). In Exp. 1, 12 steers weighing 253 kg received hGRF(1-29)NH2 in H2O at rates of 0, 3, 30 and 300 pmol.h-1.kg-1. Pumps were implanted s.c. on d 0 and removed at 1200 on d 7. Blood samples were drawn at 20-min intervals from 0800 to 1200 on d -1, 1, 3, 5, 7 and 9. Growth hormone levels were not altered by GRF treatment (P greater than .05). Solubility and volume limitations render hGRF(1-29)NH2 delivery via osmotic pumps problematical. Flow rate and duration of release of dimethyl sulfoxide (DMSO):H2) (1:1) from osmotic pumps incubated in vivo and in vitro were found to be consistent with manufacturer's specifications. Two hGRF(1-29) analogues, Ro23-7863 and 4SG-29, were dissolved in DMSO:H2O. In Exp. 2, six 222-kg steers had pumps implanted and blood samples were taken as in Exp. 1. Three steers received each analogue at a rate of 300 pmol.h-1.kg-1. Analogues had similar GH-releasing ability and GH levels differed (P less than 0.001) among days, being approximately fourfold higher on d 3, 5 and 7 than on d -1, 1 and 9. Residual analogue solutions retained full bioactivity after 7-d implantation, and in vitro biopotencies of Ro23-7863 and 4SG-29 were similar (Exp. 3). In Exp. 4, 15 wethers (means = 31.3 kg) received osmotic pumps delivering 0, 3, 15, 75 and 300 pmol.h-1.kg-1 Ro23-7863 in DMSO:H2O for 7 d. Lambs were bled at 0800 and 1400 from d -1 to 8. The latter two doses increased (P less than .01) mean GH levels 2.7- and 4.3-fold over those in control animals during the treatment period. Results demonstrate that increased GH secretion can be elicited in steers and wethers for 1 wk by continuous s.c. infusion of GRF analogues utilizing osmotic pumps.
authors.affiliation: University of Minnesota, St. Paul 55108.
authors.forename: J E
authors.initials: JE
authors.lastname: Wheaton
authors.forename: S N
authors.initials: SN
authors.lastname: al-Raheem
authors.forename: J A
authors.initials: JA
authors.lastname: Godfredson
authors.forename: J M
authors.initials: JM
authors.lastname: Dorn
authors.forename: E A
authors.initials: EA
authors.lastname: Wong
authors.forename: W
authors.initials: W
authors.lastname: Vale
authors.forename: J
authors.initials: J
authors.lastname: Rivier
authors.forename: T F
authors.initials: TF
authors.lastname: Mowles
authors.forename: E P
authors.initials: EP
authors.lastname: Heimer
authors.forename: A M
authors.initials: AM
authors.lastname: Felix
mesh_terms: D000818:Animals; D002417:Cattle / Q000502:physiology*; D013006:Growth Hormone / Q000097:blood*; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007260:Infusion Pumps; D007279:Injections, Subcutaneous; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage*; D017337:Sermorelin; D012756:Sheep / Q000502:physiology*
chemical_list: D010446:Peptide Fragments; D017337:Sermorelin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone