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  • Author: P. W. Concannon x
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Joseph P. McCann, Norman Altszuler, Jennifer Hampshire and Patrick W. Concannon

Abstract. Adult beagle bitches (20 to 101 months old) received medroxyprogesterone acetate (MPA; 75 mg/kg, im) or control vehicle at 3 month intervals. Changes in serum concentrations of GH, insulin and glucose were determined in 18 MPA-treated and 6 of 12 control bitches at 0, 2, 4, 8, 16 and 17–24 months of treatment (Exp. I). GH, LH and cortisol responsiveness to combined im injection of TRH (10 μg/kg), GnRH (10 μg/kg), and ACTH (5 μg/kg) was determined in 9 MPA-treated and 9 control bitches at 17 months of treatment (Exp. II). In Exp. I, serum concentrations of GH at month 2 (2.6 ± 0.3 μg/l), 4 (3.0 ± 0.3 μg/l), 8 (4.0 ± 1.2 μg/l), 16 (8.5 ± 1.7 μg/l), and 17–24 (21.2 ± 4.1 μg/l) of treatment were greater (P < 0.05) than pretreatment (1.4 ± 0.07 μg/l) and control (1.5 ± 0.1 μg/l) levels. The increase in GH at 2 months preceded (N = 4) or coincided (N = 2) with the development of hyperinsulinaemia and insulin resistance in 6 of the 18 treated bitches, two of which became diabetic by 17 months of MPA treatment. GH (24.6 ± 5.0 vs 11.4 ± 2.1 μg/l) and insulin (308 ± 77 vs 119 ± 9 pmol/l) concentrations were greater (P < 0.05) in older (49 ± 4 months; N = 12) than in the younger (26 ± 2 months; N = 6) treated bitches at 17–24 months of MPA treatment. In Exp. II, pretreatment concentrations of GH were increased (9.8 ± 3.0 vs 1.4 ± 0.1 μg/l, P < 0.01), cortisol levels decreased (12 ± 5 vs 72 ± 10 nmol/l, P < 0.01) and LH concentrations (0.9 ± 0.2 μg/l) unaffected in MPA-treated bitches. After injection of tropic hormones, GH was unchanged, whereas the rises in LH and cortisol levels were less (P < 0.01) in MPA-treated bitches than in control bitches. The results demonstrate that high doses of MPA increase GH concentrations within 2 months and that the GH overproduction and its diabetogenic-like effects were more pronounced in the older than in the younger treated bitches.

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P. W. Concannon, L. Dillingham and I. M. Spitz

Abstract. A bioassay for progesterone activity in dogs was established based on uterine weight (mg/kg body weight) in immature beagles administered progesterone for 10 days starting 9 days after priming with estradiol cypionate (50 μg/kg, im). Progesterone doses of 0, 0.17, 0.5, 1.5, 13.5 and 40.5 mg/kg per day, im, produced dose-dependent increases in the weights of uterine horns obtained after 5 or 10 days of treatment. The total uterine responses (horn removed at 5 days plus horn and fundus removed at 10 days) to those were (mean ± sem) 374 ± 33, 465 ± 97, 684 ± 68, 795 ± 96, 1005 ± 38, 1232 ± 15 mg/kg, respectively. Responses to the 13.5 mg/kg per day dose of progesterone in dogs given the steroid antagonist RU486 at daily oral doses of 5, 20 and 50 mg/kg were reduced to values of 634 ± 24, 464 ± 74 and 468 ± 18 mg/kg, respectively, vs 1005 ± 38 mg/kg in controls. Mean progesterone levels were 27 ± 1 μg/l. The RU486 did not produce any consistent alterations in serum cortisol levels. The results suggest that, in immature bitches, uterine weight changes can be used to bioassay progestin activity following estrogen priming, RU486 is more potent as an antiprogestin than as an antiglucocorticoid, and RU486 at oral doses of 5 and 20 mg/kg exerts submaximal and maximal antiprogestin activity, respectively, in the presence of physiological levels of progesterone.