Uterine Cyclic AMP-H³ after Estradiol and/or Propranolol

Abstract

Bolt 1970) we demonstrated the peripheral formation of estrogens in humans after injection of labeled testosterone, androstenedione and dehydroepiandrosterone. The site of this metaboIism has been localized in the liver, since simultaneous determinations in peripheral and hepatic veneous blood after application of 3H-testosterone showed the highest levels of radioaetive estrogens in the v. hepatica (Bolt, Ritzl and Bolt 1966 b). Moreover, om present results demonstrate the ability of human subcutaneous adipose tissue to transform androgens to estrogens. In vivo, however, the extent of this transformation in fat seems to be relatively low.We thank Dr. Schnellen, Dept. of Dermatology, Tübingen, for supplying the tissue specimens.There is considerable evidenee to implieate cAMp in the mechanism of action of estrogens on the uterus but whether this nucleotide acts directly as a "seeond messellj(er" or indirectly subsequent to the release and action of eatecholamines, remains uncertain (Singhal and La (reniere 1972). This report demonstrates that estradiol given to immature rats stimulates uterine cAMP-H 3 formation and the aetivities of glucose 6-phosphate and 6-phosphogluconate dehydrogenases and that pretreatment with propranolol fails to exert any significant effeet on these responses.Experiments were carried out on uteri obtained from immature female rats injected with estradiol (5 IJg/rat, i.m.), propranolol (0.3 mg/rat, i.p.) or both. Propranolol was administered 30 min before estradiol and rats were sacrificed 4 hr after the estrogen. The ability of uteri to biotransform adenosine-H3 was studied in vitro by incubating for 60 min at 37 0 C in Krebs-Ringer solution. The cAMP-H3 was isolated on polyethylene impregnated cellulose layers as described by Adachi and Kano (1970). The activity of uterine enzymes was assayed according to Singhal and La[reniere (1972) and expressed as IJmoles of substrate metabolized/hr/g of tissue x the weight of the uterus.