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The morpholine compound BRL-47672 has a chemical structure similar to that of clenbuterol and causes similar anabolic effects in rats but has no actions on beta 2-adrenoceptors in vitro. It has been argued therefore that beta 2-adrenoceptors do not mediate the anabolic effects of this family of compounds. In the present study BRL-47672 was shown to bind to rat beta 2-adrenoceptors with low affinity (dissociation constant 16 microM) relative to clenbuterol (48 nM) and to be a very weak activator of adenylyl cyclase activity in rat skeletal muscle membranes in vitro. In contrast, acute administration of the drug to anesthetized rats in vivo caused an increase in muscle adenosine 3',5'-cyclic monophosphate output, and chronic treatment of conscious rats for > 6 days caused a significant increase in weight gain (69%) accounted for by increased muscle growth. The anabolic effects of BRL-47672 were not counteracted by daily injections of the drug ICI-118551 (2 mg/day) but were prevented when the same beta 2-antagonist was administered in the diet (200 mg/kg feed, equivalent to 4.3 mg/day). The beta 1-adrenoceptor selective antagonist CGP-20712A fed in the diet (200 mg/kg feed) failed to attenuate the response to BRL-47672. These results support the conclusion that BRL-47672 has little direct action on beta 2-adrenoceptors but suggest that the compound is metabolized rapidly in vivo to a potent beta 2-agonist. Thus the stimulation of muscle growth by BRL-47672 is via beta 2-adrenoceptors, with no contribution to this response from beta 1- or beta 3-adrenoceptor activation.

This study compared the anabolic effects of clenbuterol in male and female rats and determined the relative contribution of testicular and ovarian hormones to any observed gender difference. Seventy-two 12-wk-old rats were used in a 2 x 2 x 2 factorial design in which animals were either male or female, entire or gonadectomized at 3 wk of age, and fed either a control diet or a diet containing 4 mg clenbuterol/kg feed for 8 days. Compared with entire male rats, entire females gained 64% less weight, had lighter carcasses (-36%) and gastrocnemius muscles (-62%), and had higher plasma concentrations of the catabolic hormone corticosterone (P < 0.05). Castration had a negative effect on growth in male rats, and ovariectomy had a positive effect in females, but there was still a gender difference in body weight between gonadectomized males and females, which amounted to 34% of the gender difference observed in intact rats. The density of beta 2-adrenoceptors in skeletal muscle was not different between males and females, nor was it affected by gonadectomy. Clenbuterol increased both weight gain and gastrocnemius muscle weight, with the latter response in entire and castrated male rats (+ 1.31 and + 1.17 g) being more than double that seen in entire and ovariectomized females (+ 0.58 and + 0.55 g). The downregulation response of beta 2-adrenoceptors in this muscle was remarkably consistent in all treated groups (-50% to -53%).(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

In a series of six subjects studied, a day-to-day fluctuation in urinary aldosterone excretion with a definite and characteristic pattern throughout the menstrual cycle was noted in all. The excretory level was lowest (mean value 8 · 5 [Lg. per 24 hours) 25 to I] days before menstruation, with an increase (mean value I I [Lg. per 24 hours) I] to I4 days prior to menstruation. An increase in excretion was again noticed in the second half of the cycle, with a peak excretion (mean value 23 [Lg. per 24 hours) one to five days before menstruation. This was followed in most subjects by a sharp decrease in excretion one to two days before menstruation. During the first day of menstruation a relatively low level was found, followed in some subjects by an increase on certain days of menstruation.The urinary sodium-potassium concentration ratio fluctuated during the menstrual cycle with no direct relationship to aldosterone levels. The lowest urinary sodium-potassium ratios were found in specimens one to five days before menstruation.A premenstrual increase in body weight ranging from o · 5 to 2 · 3 kg., with the maximum three to one days prior to menstruation, was noted in five subjects. This weight increase either followed or preceded the maximum observed aldosterone excretion.In one post-menopausal subject observed over a period of 26 days, the urinary aldosterone excretion ranged from 8 · 5 to I4 [Lg. per 24 hours.A detailed description of a chemical method for estimation of aldosterone in urine is given.