1. A new method for the measurement of uroporphyrinogen decarboxylase (EC 4. 1.1.37) in rat liver homogenates, with 5- carboxyl porphyrinogen as substrate, is described. 2. The administration of a diet containing 0-3% (w/w) hexachlorobenzene produces porphyria in female Wistar rats after a delay of at least 4 weeks. The development of porphyria is accompanied by a progressive fall in hepatic uroporphyrinogen decarboxylase activity to 18% of control values after 11 weeks. The features of hexachlorobenzene prophyria are consequences of this enzyme defect. 3. Feeding with hexachlorobenzene did not lead to the accumulation of iron in the liver. It is suggested that hexachlorobenzene or a metabolite acts directly to decrease the activity of the enzyme.
The aim of the present study was to investigate the effects of tamoxifen on pituitary and luteal function and on the bleeding pattern when administered continuously in the secretory phase. The study included 16 women with regular menstrual cycles followed during one control, one treatment and one follow-up cycle. Each volunteer received 20 mg tamoxifen twice daily from cycle day 18 to menstruation in the treatment cycle. The luteal phase was slightly, but significantly prolonged during treatment, and FSH, progesterone, 17-hydroxyprogesterone, 20\g=a\-dihydro progesterone, estrone, estrone sulphate and estradiol significantly elevated in comparison with corresponding data during the control cycle.The results indicate that estrogen may be of some importance for the regulation of the life span of the corpus luteum in the human. The significantly elevated levels of pregnanediol glucuronide and estrone glucuronide during the follow-up cycle are most likely a result of either a direct effect of remaining circulating tamoxifen levels on the ovary, or mediated through the increased release of FSH. If estrogens are of importance for the process of implantation, which has recently been suggested in subhuman primates, also in the human remains unclear. Studies on the effect of anti-estrogens on the endometrium during the secretory phase of the cycle are ongoing.Of the ovarian steroids, progesterone has been shown to have an indispensable role in preparing the uterine endometrium for implantation and for maintenance of pregnancy in primates including the human, whereas the importance of estradiol in these events is more controversial. It has been known for long that some derivatives of triphenyl ethylene have estrogenic properties, e.g. diethyl stilbestrol, whereas others have a more pro¬ nounced inhibitory effect on estrogen action. Among these are clomiphene citrate which is best viewed as a mixed (agonist-antagonist) estrogen re¬ ceptor probe (1), and tamoxifen in which the anta¬ gonist effect seems to dominate (2). Both clomi¬ phene citrate and tamoxifen are supposed to act through binding to the estrogen receptor.The effect of these compounds on ovarian func¬ tion if administered during the proliferative phase of the menstrual cycle has been extensively studied (1,2). The attempts to use the antagonistic effect of tamoxifen and clomiphene citrate to evaluate the physiological role of estrogen during the secretory phase of the cycle in the human, including its effect on implantation, are few. One reason may be ear¬ lier studies in rhesus monkey indicating that im¬ plantation may take place independent of estrogen support (3). This assumption may, however, not be true. Ravindranath & Moudgal (4) have recently re¬ ported that treatment with tamoxifen during the secretory phase of the menstrual cycle resulted in a dose-dependent reduction in pregnancy rate in the Bonnet monkey. The mode of action of tamox¬ ifen was not clarified. However, effects on endometrial development, follicular steroidogenesis as well as steroid rece...
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