Reduced beta adrenergic responsiveness in rats treated with estrogenic agents

Abstract

Chronic treatment with ethynyl estradiol alone (48-50 mug/kg/day) and in combination with several doses of norethynodrel either attenuated or prevented the increase in tail skin temperature accompanying sC. administration of isoproterenol (200 mug/kg b.wt.) to male and female rats. Dietary administration of an oral contraceptive containing norethynodrel and mestranol (7.5 mg/kg of food) was also accompanied by an attenuated response to isoproterenol. Attenuation of the tail skin temperature response was present in all groups after 3 to 5 weeks of treatment but was detectable in the oral contraceptive-treated group after 1 week of treatment. All steroids and combinations, except norethynodrel administered alone (154 mug/kg/day), reduced body weight gain.

PIP: 2 experiments designed to test beta adrenergic responsiveness of the tail skin temperature of rats treated with an estrogenic agent, a progestational agent, and both combined are reported. In the 1st experiment, 24 male rats were divided into 4 groups: 1) controls, 2) a 10 mm silastic tube containing norethynodrel (crystalline) was implanted, 3) a silastic tube containing crystalline ethinyl estradiol was implanted, and 4) both drugs were implanted. At 15 weeks the tail temperature of the rats and their colon temperature were observed for 1 hour. A 200 mcg injection of 1-isoproterenol/kg was given and the rats observed for an additional 2 hours. 22 weeks after implantation the rats were sacrificed and silastic tubes weighed in order to calculate the daily drug dose. In the 2nd experiment 30 female rats were divided into 5 groups: 1) controls, 2) a 20 mm length of silastic tube containing crystalline norethynodrel implanted beneath the shoulder blades and a 10 mm length of tubing containing crystalline ethinyl estradiol implanted beneath the skin covering the skull, 3) a 10 mm length of tubing containing norethynodrel plus a 20 mm length containing ethinyl estradiol, 4) a 10 mm length of tubing containing norethynodrel and a 10 mm length containing ethinyl estradiol, and 5) the oral contraceptive Enovid with 5.0 mg norethynodrel and .075 mg mestranol mixed in with food. Temperature observations were made at the end of week 1 after implantation, Week 3, and Week 5. Room temperature was maintained at 23 degrees C. During Week 12 the tail temperatures were again observed but in a room kept at 30 degrees C for 60 minutes. 100 mcg phenylephrine was administered at the end of this time to determine whether responsiveness of tail skin temperature to an alpha adrenergic agonist differed among the groups. Food intake was measured during Week 18. The rats were then sacrificed and daily rate of drug intake computed. Chronic treatment with ethinyl estradiol alone (48-50 mcg/kg/day) and in combination with several doses of norethynodrel either attenuated or prevented the increase in tail skin temperature accompanying sc administration of isoproterenol to male and female rats. Dietary administration of Enovid (7.5 mg/kg of food) was also accompanied by an attenuated response to isoproterenol. This reponse was detectable in all groups after 3-5 weeks treatment but was detectable after 1 week of the start of oral contraceptive treatment. All steroids and combinations, except norethynodrel administered alone (154 mcg/kg/day), reduced body weight gain.