Biomedical subjects
Publications and source records attributed to Y Okatani.
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The administration of 100 micrograms 2-hydroxyestrone (2-OHE1) or 2-hydroxyestradiol-17 beta (2-OHE2) at 0900h or 1000h in the morning of proestrus into normal 4-day cycling rats results in suppression of the preovulatory LH surge in the afternoon of that day. The LH-RH content of the median eminence in control rats decreases sharply in the afternoon from elevated noon levels. However, the catechol estrogen-treated rats do not show this decrease. These results indicate that the catecholestrogens block the preovulatory LH surge by preventing the release of LH-RH from the median eminence, but do not interfere with the synthesis and accumulation of LH-RH. Furthermore, injections of non-uterotropic 2-OHE1 twice at 30 minutes intervals into ovariectomized rats fail to affect the LH tonic secretion by 180 minutes after the initial injection. These data indicate that catechol estrogen interferes with the brief neuronal triggering phase necessary for LH-RH release, but does not affect the LH tonic secretion which is an estrogen-independent process.
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Cycling rats injected with 2-hydroxyestrone or 2-hydroxyestradiol at 09.00 or 10.00 h in the morning of proestrus do not express the normal preovulatory LH surge in the afternoon of the day. The LHRH content of the median eminence in control animals decreases sharply in the afternoon from elevated noon and morning levels. The catechol estrogen-treated rats fail to show the decrease. Thus the catechol estrogens block the LH surge at its usual time by influencing the changes in the concentration of LHRH in the median eminence on proestrus. Since the catechol estrogens have short biological half-lives, their effect on the LHRH content in the afternoon must originate in the morning at the time of the endogenous estradiol (E2) peak. These results have implications in the physiological processes responsible for the positive feedback of estradiol on the preovulatory LH surge in the rat.
Catechol estrogens, administered iv to cycling rats on the morning of proestrus, were able to block the preovulatory PRL surge on the afternoon of the same day. Only catechol estrogens with a low affinity for the estrogen receptor, such as 2-hydroxyestrone and 2-hydroxyestradiol-17 alpha were effective in this respect, while the estrogenic catechol estrogen 2-hydroxyestradiol was unable to influence the PRL surge. The effectiveness of the PRL surge abolition was highly dependent on the state of the endogenous estradiol levels at the time of administration. Only doses given just before the peak secretion of estradiol were effective in blocking the PRL surge. Despite similarities in the inhibition of the preovulatory LH and PRL surges by catechol estrogens, these are considered to occur by different mechanisms because the LH secretion is blocked by all catechol estrogens, while the PRL surge is affected only by catechol estrogens with no estrogen agonist properties. The catechol estrogen blockade of the PRL surge may have physiological parallels and provides a useful probe of the mechanisms of the estrogen-PRL axis.
So as to evaluate metabolism of catecholestrogens during pregnancy, changes in plasma unconjugated estradiol (E2), estrone (E1), 2-methoxyestradiol (2-mE2) and 2-methoxyestrone (2-mE1) concentrations were measured after a bolus injection of 40mg of estrone-sulfate (E1-S) or 100mg of dehydroepiandrosterone-sulfate (DHA-S) to normal pregnant women near term. The injection of E1-S resulted in a marked rise in plasma 2-mE1 levels followed by a rapid marked increase in the plasma E1 concentration. The injection of DHA-S produced a small increase in the plasma 2-mE2 levels in spite of a marked increase in the plasma E2 concentration. No significant correlation between E2 and 2-mE2 was found, however, significant correlations between E1 and 2-mE1, between E1 and 2-mE2 and between 2-mE2 in in both groups were demonstrated. The marked increase in 2-mE1 compared to a small increase in 2-mE2 after DHA-S injection indicates that E2 may participate in the formation of catecholestrogen via its conversion to E1 during pregnancy. These results suggest that the main route for the formation of catecholestrogen is via E2----E1----(2OHE1)----2-mE1 in normal pregnancy near term.
Administration of 100 micrograms 2-hydroxyestrone (2-OHE1) on the morning of proestrus to 4 day cycling rats resulted in suppression of the preovulatory LH surge. The greatest response was observed when the injection of 2-OHE1 coincided with plasma estradiol levels that were close to but not at their maximal proestrus levels. Injection of 100 micrograms 2-hydroxyestradiol-17 beta (2-OHE2-17 beta) effectively inhibited the LH surge when given at 0800 or 0900h, but not when injected at 1000 or 1200h. Non estrogenic 2-hydroxyestradiol-17 alpha was effective in suppressing the LH surge when given at 0900 or 1000h. Neither 2-OHE1 nor 2-OHE2-17 beta interfered with LH secretion in response to LH-RH administration, indicating that the inhibitory action of the catecholestrogen is exercised at the hypothalamic level. However, 2-OHE1 given five times following the implantation of an estradiol capsule in ovariectomized rats had no effect on the LH surge elicited on the second day. These data indicate that catecholestrogen interferes with the brief neuronal triggering phase necessary for LH-RH release, but not the sensitization phase of positive feedback of estrogen on phasic LH secretion. The evidence also indicates that the action does not involve conventional competition for the estradiol receptor.
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Injection of 100 micrograms 2-hydroxyestrone (2OHE1) at various times on the morning of proestrus into normal 4-day-cycling rats results in abolition of the preovulatory LH surge in a number of animals tested. The greatest response was observed when the administration of 2OHE1 coincided with endogenous estradiol (E2) levels that were close to but not at their maximal proestrous levels. The catechol estrogen failed to abolish the LH surge if given much earlier or after the E2 maximum had already been reached. The effectiveness of 2OHE1 inhibition of the LH surge was greatly increased by the administration of 1 microgram E2 1 h before the catechol estrogen. 2OHE1 did not interfere with LH secretion in response to LHRH administration, indicating that the inhibitory action of the catechol estrogen is exercised at the hypothalamic level. In contrast to its inhibition of the positive feedback, 2OHE1 administered either before or after the injection of E2 to ovariectomized rats had no effect on the negative feedback of the hormone on pituitary LH secretion. The narrow and specific "time window" on proestrus when an injection of 2OHE1 results in the abolition of the preovulatory LH surge and its relation to the endogenous E2 preovulatory secretion suggest that the catechol estrogen interferes with a brief neuronal triggering event obligatory for LHRH release. The evidence also indicates that this action does not involve conventional competition for the E2 receptor.
Four-day cycling rats equipped with intracardiac catheters were injected with 2-hydroxyestradiol-17 beta (2OHE2-17 beta) at 0800, 0900, 1000, and 1200 h on the morning of proestrus. The administration at 0800 and 0900 h resulted in abolition of the afternoon preovulatory LH surge in virtually all animals. Injections given at 1000 and 1200 h were ineffective in this respect. The isomeric catechol estrogen 4-hydroxyestrone effectively inhibited the LH surge when given at 0900 h, but not if injected at 1000 or 1200 h. In contrast, the nonestrogenic 2-hydroxyestradiol-17 alpha was effective in blocking the LH surge when given at 0900 or 1000 h. Rats treated with 2OHE2-17 beta at 1000 h responded normally to exogenous LHRH administration in the afternoon, indicating that the action of 2OHE2-17 beta is at the hypothalamic level. 2OHE2-17 beta and 4-hydroxyestrone, which are potent estrogens, may act in this instance first as estrogen agonists, advancing the "time window" when their catechol antagonist properties in blocking the LH surge can be functional. The nonuterotropic 2-hydroxyestradiol-17 alpha and 2-hydroxyestrone act solely as catechol estrogens and inhibit the preovulatory LH surge if administered at a time when they be present during this physiological window, which is thought to involve events at the estrogen-catecholaminergic interphase.
A simultaneous microdetermination of unconjugated estrone, estradiol, estriol and estetrol in serum or amniotic fluid by High Performance Liquid Chromatography with an Amperometric Detector is described. Steroids in serum or amniotic fluid were extracted with 10 volumes of ethyl ether, and then ether extract was evaporated to dryness under N2 gas. After defatting with a mixture of 50% methanol/n-hexane, the methanol phase was evaporated to dryness under N2 gas. The residue was applied to microcolumn packed with 2 ml volume of Sephadex LH-20 in the eluting solvent benzene/methanol (85:15). Fractions contained estrone and estradiol; estriol and estetrol were collected and then evaporated to dryness under N2 gas. The sample solution was applied to HPLC using a reverse phase ODS column and acetonitrile: 0.1M KH2 PO4 47:53 for estrone and estradiol fraction, and 30:70 for estriol and estetrol fraction as a mobile phase, respectively. The fraction of each estrogen was separated completely within a 20 minute period. The limit of detection of estrone, estradiol, estriol and estetrol was 50 pg, respectively.
In my clinic, Solganal-B-Oleosum was administered to the patients with bronchial asthma from 1955 up to 1973, covering a period of 19 years, and statistical observation has been done. Several clinical results are presented. 1) In 1,056 cases, markedly improved 40.8%, improved 32.8%; clinically effective ratio: total 73.6%. Others: a few somewhat improved and unimproved cases, then inconsiderable aggravated cases. 2) The longer the period from the age of onset to the beginning of treatment, the lower the efficiency; the shorter the period, the higher the efficiency. 3) The group of light severity revealed high efficiency; and according to the grade of severity the efficiency decreased. 4) Sex, age, age of onset, disposition of asthma, etc., resulted in no clear relation to the effectiveness. 5) Side effect revealed 2.3% skin eruption, and then a few cases of proteinuria, stomatitis, gingivitis, etc. There was no case of severe, critical disorder. 6) In other cases, long-term effectiveness after finishing the Solganal treatment was pursued. A trial of additional injection for several years after finishing the treatment was also studied. Serum gold concentrations in the course and after finishing the main course etc., were measured.