J. Anim Sci.
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J. Anim Sci. 1988. 66:2876-2885.
© 1988 American Society of Animal Science
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Use of Osmotic Pumps for Subcutaneous Infusion of Growth Hormone-Releasing Factors in Steers and Wethers1

J. E. Wheaton2,3,, S. N. Al-Raheem4, J. A. Godfredson, J. M. Dorn, E. A. Wong, W. Vale5, J. Rivier5, T. F. Mowles6, E. P. Heimer7 and A. M. Felix

University of Minnesota, St. Paul 55108

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 > .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):H2O (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 < .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 (x = 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 < .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.

Footnotes

1 Published as paper No. 15,960 of the scientific journal series of the Minnesota Agric. Exp. Sta. on research conducted under Minnesota Agric. Exp. Sta. Project No. 0302-4816-75. Experiments were funded in part by Hoffmann-La Roche, Inc.,

2 Appreciation is expressed to NIADDK for providing growth hormone radioimmunoassay preparations, and to J. M. Marcek, K. M. Carlson, D. J. Lang, T. Egan, T. Lambros and L. J. Keck for their technical assistance.

3 Send reprint requests to: Dept. of Anim. Sci., 495 Anim. Sci./Vet. Med. Bldg. 1988 Fitch Ave.

4 Present address: Dept. Anim. Prod., Univ. of Bagdad, Iraq.

5 Peptide Biol. Lab., The Salk Inst., San Diego, CA 92138.

6 Hoffmann-La Roche, Inc., Dept. Anim. Sci. Res., Nutley, NJ 07110.

7 Peptide Chemistry Hoffmann-La Roche, Inc., Nutley, NJ 07110.






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Copyright © 1988 by the American Society of Animal Science.