Potency Of Estradiol Research Articles

Estradiol transfer from male big brown bats (Eptesicus fuscus) to the reproductive and brain tissues of cohabiting females, and its action as a pheromone

The powerful estrogen, 17β-estradiol, has been found to pass from male excretions to the reproductive organs, brain, and other tissues of cohabiting females in laboratory mice. The current studies were designed to examine whether this phenomenon also occurs in big brown bats (Eptesicus fuscus), a mammal appropriate for testing cross-species generality because of its phylogenetic distance from mice. When tritiated estradiol (3H-E2) was administered directly on the nasal area of adult female bats, radioactivity was reliably observed in the uterus and ovaries, and also in the brain and other tissues. When 3H-E2 was applied to the skin, radioactivity was observed in reproductive and other peripheral tissues. We injected male bats with minute quantities of 3H-E2 and housed each of them directly with groups of adult females for 48h. We then measured radioactivity in male and female bat tissues. In each of several replications of one male housed with three females, radioactivity was reliably observed in the uterus of all females, and in many other tissues in almost every female. Measurement in the organs of males directly exposed to 3H-E2 showed high levels of radioactivity in the testes and especially the epididymides. These data indicate that estradiol is transferred from males to females, likely via absorptions from males’ excretions and potentially also via intravaginal exposure during mating. Given the potency of estradiol in regulating female reproductive physiology and behavior, our data strongly suggest the potential for pheromonal action whereby male mammals induce sexual receptivity and ovulation in females.

Coactivator peptides have a differential stabilizing effect on the binding of estrogens and antiestrogens with the estrogen receptor.

The effectiveness of estrogens in stimulating gene transcription mediated by the estrogen receptor (ER) appears to depend on ER interactions with coactivator proteins. These coactivators bind to ER when it is liganded with an estrogen agonist, but not when it is liganded with an estrogen antagonist. Because estrogen agonists are known to induce a conformation in ER that stabilizes coactivator binding, we asked whether coactivator binding to ER causes a reciprocal stabilization of agonist ligand binding. We used a fluorescent ligand for ER, tetrahydrochrysene-ketone, to monitor the rates of ligand dissociation from ERalpha and ERbeta, and to see how this process is affected by the p160-class coactivator, steroid receptor coactivator-1 (SRC-1). We used a 15-amino acid peptide corresponding to the second nuclear receptor box LXXLL motif in SRC-1 (NR-2 peptide), which is known to interact with the ER ligand-binding domain, a mutant peptide with an LXXAL sequence (NR-2A peptide), and a 203-amino acid fragment of SRC-1, termed the nuclear receptor domain (SRC1-NRD), embodying all three of the internal NR boxes of this protein. Both the NR-2 peptide and the SRC1-NRD fragment markedly slow the rate of dissociation of the agonist ligands tetrahydrochrysene-ketone, estradiol, and diethylstilbestrol, increasing the half-life of the ER-agonist complex by up to 50- to 60-fold. The SRC1-NRD has much higher potency in retarding ligand dissociation than does the NR-2 peptide; it is maximally effective at 30 nM, and it appears to bind with the stoichiometry of one SRC1-NRD per ER dimer. The peptides had little effect on the dissociation rate of antagonist ligands. Consistent with these results, we find that increasing the concentration of SRC-1 in cells by transfection of an expression plasmid encoding SRC-1 causes a 17-fold increase in the potency of estradiol in an estrogen-responsive reporter gene transcription assay. Thus, there is multifactorial control over receptor-coactivator interaction, its strength being determined by the agonist vs. antagonist nature of the ligand and the particular structure of the agonist ligand, and by the receptor subtype and the NR box sequence. The stabilizing effect of coactivator on ER-agonist ligand complexes may be important in determining the potency of estrogen agonists in a cell and may also underlie the tissue-selective pharmacology of certain synthetic estrogens.

Antioxidant potency of estradiol in rat hepatocytes and ito cells

Antioxidant potency of estradiol in rat hepatocytes and ito cells

Negative feedback potency of estradiol is increased in orchidectomized sheep during chronic nutrient restriction.

The effect of nutrient restriction on serum concentrations of the gonadotropins, on the pattern of LH secretion, and on sensitivity to estradiol (E2) was assessed in orchidectomized sheep (wethers). Thirty-six wethers (initial weight = 42.3 +/- 0.6 kg) were fed to gain, maintain, or lose body weight (feeding groups G, M, and L, respectively; n = 12 wethers/group). After 7 wk of controlled feeding, G, M, and L wethers weighed 57.0 +/- 1.7, 42.5 +/- 0.6, and 36.6 +/- 0.8 kg, respectively. At the end of controlled feeding, serum concentrations of LH and FSH in M and L wethers were significantly higher than levels in G wethers. During Days 51-54 of controlled feeding, six animals from each feeding group received E2 or vehicle as a continuous infusion. The pattern of LH secretion was assessed 48 h after initiation of infusion. Although E2 infusion did not affect (p > 0.05) LH pulse frequency in G and M wethers, pulse frequency was reduced (p < 0.05) in L wethers receiving E2. These data indicate that serum concentrations of gonadotropins are increased in wethers fed to maintain or lose body weight. In addition, the negative feedback potency of E2 is enhanced during prolonged weight loss.

3,17 beta-Dihydroxy-20,21-epoxy-19-norpregna-1,3,5(10)-trienes: synthesis, rearrangement, cytotoxicity, and estrogen-receptor binding.

Diastereoisomers of 3,17 beta-dihydroxy-20,21-epoxy-19-norpregna-1,3,5(10)-triene have been prepared as potential antitumor agents. Both isomers undergo the base-catalyzed Payne rearrangement. The isomers were cytotoxic to mammalian cells in culture and were able to displace [3H]estradiol from binding sites in rat uterine cytosols with 1/7 and 1/70 the potency of estradiol. The reasons for this difference are discussed.