Estradiol-17 Beta Receptors Research Articles

A estradiol-17beta receptor in the reproductive system of the female of Octopus vulgaris: characterization and immunolocalization.

In this study, for the first time we have identified an estradiol-17beta receptor (ER) in the reproductive system of the female of Octopus vulgaris. Scatchard analysis revealed that one binding component with high affinity and low capacity for the ligand was present in the cytosol, but not in the nuclear extract of the ovary and the oviduct. A steroid specificity competition assay showed that 3H-estradiol-17beta binding activity showed a preference for estradiol-17beta. DNA-cellulose chromatography confirmed the presence of one 3H-estradiol-17beta binding component. By using antibodies anti ER (578-595), we have localized by Western blotting one band of about 70 kDa. ER immunoreactivity has been localized in the nuclei of the follicle cells of the ovary, in the nuclei of the epithelium lining the proximal portion of the oviduct and in the nuclei, and in the cytoplasm of the inner region of the oviducal gland and in the cytoplasm of the outer region of the oviducal gland. These data, taken together, provide evidence that in Octopus vulgaris the ER has biochemical and immunohistochemical characteristics resembling those of ER in vertebrates.

C-nor-9,11-secoestranes as modified estrogens and fertility regulation.

The synthesis of C-nor-9,11-secoestradiol (4) has been achieved from 17 beta-acetoxy-11-chloro-3-methoxy-C-nor-9,11-secoestra-1,3,5(10)-tr ien-9-one (1) through a sequence of reactions without affecting the stereochemistry of estradiol-17 beta. Removal of the 9-keto function of 1 by hydrogenolysis and its subsequent treatment with Na/NH3 gives C-nor-9,11-secoestradiol 3-(methyl ether) (3), which has been demethylated under alkaline conditions to furnish C-nor-9,11-secoestradiol (4). Pyridinium chlorochromate oxidation of 3 gives the corresponding 17-ketone 6. Jones' oxidation of 4 to the ketone 5 and reaction of 5 and 6 with lithium acetylide gives corresponding 17 alpha-ethynyl derivatives 7 and 8. Relative binding affinity to estradiol-17 beta receptors and uterotropic, antiuterotrophic, and antiimplantation activities of compounds 3-8 have been studied. The effect of conformational flexibility on ligand-receptor interaction of these compounds is discussed.

Effects of season and sex on the distribution of cytosolic estrogen receptors within the brain and the anterior pituitary gland of sheep.

This study was undertaken to evaluate the effects of season and sex on the distribution of cytosolic estradiol-17 beta receptors (E2-receptors) within multiple regions of the ovine brain and the anterior pituitary gland. Our data confirm the existence of a saturable, high-affinity receptor specific for estradiol-17 beta (E2) in the hypothalamus and anterior pituitary gland. The concentrations of E2-receptors in tissues from castrated ewes and rams killed in December (breeding season) and May ( nonbreeding season) were determined by incubating cytosols with a saturating concentration of [3H] E2. For both sexes, the anterior pituitary gland contained the highest concentration of E2-receptor. Within the brain, the highest concentrations of E2-receptor were in the hypothalamus and preoptic area (POA), and within the hypothalamus, the median eminence-infundibular stalk (ME) contained a higher concentration of E2-receptor than the anterior and posterior hypothalamus. The numbers of E2-receptors in the anterior hypothalamus and ME of ewes were 2- 3X those for rams. In ewes, there was little seasonal difference in the numbers of E2-receptors in the POA, anterior hypothalamus and ME. In rams, there was little seasonal difference in the numbers of E2-receptors in the POA and anterior hypothalamus. For both sexes, there were fewer E2-receptors in the anterior pituitary gland and posterior hypothalamus in May than in December. Thus, during the nonbreeding season, the major neuroendocrine site of action of E2 probably is within the brain, specifically in the POA, anterior hypothalamus and ME of the ewe, and in the POA and the anterior hypothalamus of the ram. These data do not support a mechanism whereby the increased sensitivity to sex steroids during the nonbreeding season is due to enhanced numbers of E2-receptors.

Pathogenesis and treatment of infant skin strawberry hemangiomas: clinical and in vitro studies of hormonal effects.

Corticosteroid treatment of infant strawberry hemangiomas produced premature regression of growing lesions in patients less than a year of age, but not in patients with cavernous or port-wine hemangiomas. Abnormally elevated serum estradiol-17 beta levels were found in strawberry hemangiomas, fourfold higher than in control, cavernous, and port-wine hemangiomas which were adjusted for age and sex of the patients. Specific estradiol-17 beta receptor binding activity was studied in biopsy tissues obtained from normal prepubertal skin and skin from various kinds of hemangiomas. Minimal specific estradiol-17 beta binding activity was detected in tissues of normal skin and involuting strawberry, cavernous, or port-wine hemangiomas. Abnormally high levels of specific estradiol-17 beta binding sites were demonstrated by receptor assays and by in vitro tissue culture technique in nine tissue samples obtained from strawberry hemangiomas, seven of which responded definitely or probably to corticosteroid therapy. The in vitro estradiol-17 beta binding activity in these tissue explants was inhibited by low (5 micrograms/ml) and high (100 micrograms/ml) doses of cortisone. The present data seem to suggest that there may be a causal relationship between the presence of elevated serum E2 and specific estradiol-17 beta receptors in the pathogenesis of strawberry hemangiomas and in response to corticosteroid treatment of the hormone-sensitive hemangiomas.

The metabolism of diethylstilbestrol.

This literature review presents available data on the metabolism of diethylstilbestrol (DES) to shed light on the fate and the mechanism of toxicity of this compound. Biotransformation effects reviewed include conjugation reactions of DES such as glucuronide formation in vivo and in vitro, enterohepatic circulation of DES and its glucuronide, and formation of steroid sulfatases and sulfates; oxidative metabolism of DES (aromatic hydroxylation followed by methylation); and species differences in DES metabolism. Excretion curves for 12 animal species show vast differences; whereas urinary excretion predominates in humans, chimps, rhesus monkeys, and guinea pigs; rats, hamsters, and mice show predominately fecal elimination. The difference among species seems due to capability of biliary excretion. A molecular weight threshold seems to exist, and this may account for the varying remnants of DES housed in different species' organs. Placental transfer is another major problem. Fetuses of many species seem capable of glucurondizing DES. The formation of reactive metabolites (i.e., affinity for estradiol 17-beta receptor attachment and affinity for other proteins bound by estrogen) through oxidative biotransformation suggests that DES metabolites affect hepatic systems and may activate or transform cells to malignancy. Theories of the organotropism of DES carcinogenicity are presented, as well as a discussion of the fate of DES in the environment.

Contribution of functional groups of 19-nor-progestogens to binding to progesterone and estradiol-17beta receptors in rabbit uterus.

The structural elements of 19-norprogestogens which may be essential for binding to progesterone and estradiol-17beta(E2) receptors were investigated in the rabbit uterine cytosol. The kinetic study showed that 19-nor-progestogens are competitive inhibitors of progesterone-receptor (8S) binding and E2-receptor binding. The affinities of steroids for the progesterone receptor were as follows: norethindrone (Ki of 2.3 X 10(-9)M) greater than 5alpha-dihydronorethindrone greater than norethindrone acetate greater than lynestrenol greater than 17alpha-ethynyl-estra-4-ene-3beta, 17beta-diol greater than ethynodiol diacetate (Ki of 1.3 X 10(-7) M). The affinities of steroids for the E2 receptor were as follows: ethynodiol diacetate (Ki of 1.3 X 10(-7)M) greater than 17alpha-ethynyl-estra-4-ene-3beta, 17beta-diol greater than norethindrone acetate greater than norethindrone greater than 5alpha-dihydronorethindrone greater than lynestrenol (Ki of 8.4 X 10(-7)M). The results indicate that 3-ketone and 17beta-hydroxyl groups, and the plane of ring A/B of 19-norprogestogen are important for binding to the progesterone receptor. The affinities of 19-nor-progestogens for the E2 receptor were very weak. Their affinities for the E2 receptor increased with addition of acetate or hydroxyl groups at the 3beta and 17beta positions, and were decreased by the elimination of a 3 oxygen function or the reduction of ring A.