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Department of Biological Sciences, Allergan Inc., Irvine, California, USA
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Department of Biological Sciences, Allergan Inc., Irvine, California, USA
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Department of Biological Sciences, Allergan Inc., Irvine, California, USA
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Department of Biological Sciences, Allergan Inc., Irvine, California, USA
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Department of Biological Sciences, Allergan Inc., Irvine, California, USA
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Previous studies in this laboratory have suggested that the isolated uterus from non-pregnant mice has a prostaglandin F and a thromboxane receptor population similar to that found in human myometrium. The aim of this study was to investigate any regional variation in myogenic activity ) and the and responsiveness to prostaglandin F2α (PGF2α thromboxane mimetic U46619 in the mouse uterus taken during different stages of the oestrous cycle and during pregnancy. Uterine samples from BKW mice were taken from different anatomical segments along the length of each uterine horn and set up for superfusion at 2 ml/min with Krebs solution (containing 1 μM indometacin) at 37 °C, and gassed with 95%O2/5%CO2. Responses (area under the curve) are expressed as a percentage of the final contraction induced by hypotonic shock. Data are expressed as the means ± s.e.m. of n=5–12 and were analysed using Student’s paired t-test or two-way ANOVA with a Bonferroni post hoc test. Regional variation in myogenic activity was observed in all tissues studied except those taken during labour. These tissues displayed significantly greater myogenic activity than tissues taken at late gestation and at all stages of the oestrous cycle. Tissues from pregnant animals were generally more responsive to U46619 and PGF2α than tissues taken from non-pregnant animals. Tissues taken from the upper segment of the uterine horn were more responsive to both agonists during the oestrous cycle. The findings demonstrated that the hormonal milieu and site of excision are important for myogenic activity and responsiveness.
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ABSTRACT
Twenty two patients with advanced carcinoma of the prostate have been treated for up to 3 months with the slow-release (depot) formulation of the luteinizing hormone-releasing hormone (LHRH) agonist ICI 118630. Patients were randomized to receive one of three different doses of ICI 118630 of 0·9, 1.8 or 3.6 mg. The depot preparation was injected subcutaneously every 4 weeks. At the highest dose, the concentration of testosterone in serum was significantly reduced to castrate values after 2–3 weeks of therapy. The smaller doses of ICI 118630 (1.8 or 0.9 mg every 4 weeks) similarly reduced serum testosterone concentrations although, at the lowest dose, testosterone values were not suppressed in all patients during the first month. Hormonal changes were accompanied by subjective clinical improvement in symptomatic patients and there were no significant side effects. The data clearly demonstrate the considerable therapeutic potential of ICI 118630 in the depot formulation for the treatment of advanced carcinoma of the prostate.
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SUMMARY
Oestradiol-17β, diethylstilboestrol (DES), dl-dihydrodibutylstilboestrol (dl-DHBS) and meso-dihydrodibutylstilboestrol (meso-DHBS) were injected intramuscularly into male Sprague-Dawley rats in a daily dose of 100 μg for a period of 10 days. Oestradiol-17β and DES decreased the weight of the prostate and seminal vesicles to the same extent, whereas meso-DHBS was less effective. dl-DHBS was almost inactive. Only oestradiol-17β and DES caused a decrease in the weight of the testes. The adrenal glands increased in weight after administration of either oestradiol-17β, DES or meso-DHBS.
Four hormones in the plasma were measured: testosterone, androstenedi-one, prolactin and interstitial cell-stimulating hormone (ICSH). DES decreased the plasma concentration of both ICSH and testosterone. Oestradiol-17β and meso-DHBS administration resulted in a lowering of the plasma testosterone concentration with no effect on ICSH. Oestradiol-17β, DES and meso-DHBS markedly increased plasma prolactin concentrations. dl-DHBS appeared to have little biological effect causing only very small changes in all the parameters investigated.
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SUMMARY
Forty-two members of a Lesbian organization volunteered to participate in a study designed to seek organic abnormalities. Urinary levels of oestrone, oestradiol, oestriol, pregnanediol, 17-oxosteroids, 17-hydroxycorticosteroids, testosterone and epitestosterone were determined. No consistent pattern of hormonal abnormality emerged. Thirty-seven of the subjects completed the Eysenck Personality Inventory and 39 completed a questionnaire. The mean neuroticism score for the group was significantly higher and the mean extraversion score was significantly lower than in the normal population. This finding of dysthymia was reflected to some extent by the high incidence of past psychiatric treatment for anxiety and/or depression.