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Highly Improved Precision of the Hypophysectomized Female Rat Body Weight Gain Bioassay for Growth Hormone by Increased Frequency of Injections, Avoidance of Antibody Formation, and Other Simple Modifications^*

Pituitary Hormones and Antisera Center, Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center Torrance, California 90509

Address requests for reprints to: A. F. Parlow, Ph.D., Pituitary Hormones and Antisera Center, Harbor-UCLA Medical Center, 1000 West Carson Street, Torrance, California 90509.

Abstract

Mediocre precision has been a frustrating feature of the hypophysectomized female rat body weight gain bioassay for GH, especially human GH (hGH), in the original procedural format of injections once daily, ip, for 10–14 days. Consequently, the principal conditions that influence the bioassay's precision were identified and appropriately modified, by detailed systematic analysis of the daily body weight gain response to treatment with bovine GH (bGH) and hGH. Under identical conditions, the slope and precision of dose-response curves for hGH were markedly inferior to those for bGH. This prompted revision of the injection frequency for hGH to four times daily, sc. Dramatic improvement in slope and precision for hGH resulted, nearly equal to the excellent slope and precision attained for bGH with twice daily injections, sc. In addition, direct and indirect assessment of GH antibody formation pinpointed day 8 as the time of onset of growth-neutralizing antibodies, which are deleterious to precision and accuracy. Accordingly, the injection period was limited to 7 days. A warm environment of 31–32 C to sustain optimal animal health and responsiveness and objective specifications for selection of animals were also used. These modifications, incorporated into standardized procedures (four times daily injections, sc, 7 consecutive days, for hGH; twice daily injections, sc, 7 consecutive days, for bGH) produced a , the index of precision, which hovered on the highly respectable bioassay value of 0.2 consistently and reliably. The demonstration of differing performance characteristics and differing immunogenicities of bGH and hGH in the rat invalidates the use of one as the reference standard for the bioassay of the other, and beclouds the quantitative meaning of all prior data derived in that way. (Endocrinology 120: 2582–2590, 1987)

Footnotes

^* This work was supported by NIDDK Contract AM-2–2213 and institutional funds of the Research and Education Institute of the Harbor-UCLA Medical Center, Torrance, CA.

Received November 6, 1986.

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