Oestrone conjugate and LH/CG were measured in the urine of 4 Goeldi's monkeys during 6 pregnancies. The gestational length was a mean of 148.8 days from the post-partum LH/CG peak to parturition. CG was first detected a mean of 18.8 days after the LH/CG peak and values remained elevated for a mean of 44.8 days. Three different gonadotrophin assays were used to detect LH/CG: the mouse in-vitro interstitial cell bioassay, a mixed heterologous LH RIA, and a monkey CG RIA. The mouse in-vitro interstitial cell bioassay was useful for measuring both the LH peak which occurred post partum and the CG concentrations during pregnancy. However, both immunoassays were inconsistent in measuring LH due to poor cross-reactivity or lack of specificity; CG concentrations were measurable. Oestrone conjugates became elevated at the time of the LH/CG peak and concentrations continued to increase throughout pregnancy, reaching peak levels before parturition. The postpartum interval, pregnancy and parturition can therefore be monitored in the Goeldi's monkey by the use of urinary assays: those for bioactive LH and immunoreactive oestrone conjugates to determine the post-partum LH peak and those for immunoreactive LH/CG and immunoreactive oestrone conjugates to follow pregnancy and parturition.

Various substrates of rat liver microsomal UDP-glucuronosyltransferase were classified in vitro as preferred substrates of either 3-methylcholanthrene- or phenobarbital-inducible enzyme forms. Microsomal UDP-glucuronosyltransferase activities towards a third group of substrates (including oestrone, phenolphthalein, paracetamol and oxazepam) are not markedly altered by treatment with either 3-methylcholanthrene or phenobarbital. Some substrates of the 3-methylcholanthrene- and phenobarbital-inducible enzyme activities were selected to evaluate the importance of multiple enzyme forms for glucuronide formation in the intact cell. The metabolism of these compounds was compared in isolated hepatocytes from untreated controls and from rats treated with 3-methylcholanthrene (MC-hepatocytes) or phenobarbital (PB-hepatocytes). Glucuronidation of 1-naphthol and 3-hydroxybenzo[a]pyrene was chiefly enhanced in MC-hepatocytes (greater than 2-fold), whereas glucuronidation of chloramphenicol and bilirubin was chiefly enhanced in PB-hepatocytes. These observations are in agreement with differential induction of UDP-glucuronosyltransferase activities in vitro suggesting that, besides other factors such as cofactor supply, physiological activators, etc., the levels of the multiple enzyme forms are critically determining glucuronide formation in the intact cell.

The aim of this study was to assess how effectively the Rovumeter, designed for the volumetric self-sampling of cervicovaginal fluid (CVF), can be used to locate the minimum period of potential fertility (PPF) during ovulatory cycles. A multicentre, prospective study was undertaken of volunteers (attending natural family planning clinics) over three consecutive, apparently normal, menstrual cycles. All women collected daily samples of early morning urine and CVF and recorded the volumes (to the nearest 1.0 and 0.1 ml respectively). The concentrations of oestrone glucuronide (EG), luteinizing hormone (LH) and pregnanediol glucuronide (PG) were measured in all samples of early morning urine by immunoassay. A preliminary data set was used to optimize an algorithm to detect the start and end of potential fertility from the volumes of CVF. The end-points used were the normality of each menstrual cycle from its length, the length of luteal phase, and concentrations of EG, LH and PG, the start and end days of potential fertility from CVF volumes, and the minimum PPF, which was defined as the day of the LH peak minus 3 to day plus 2 inclusive. Overall, 72 women (median age 30 years, range 24-38) were recruited from three centres (23 from Birmingham, 24 from Milan, 25 from Santiago) and contributed data from 235 menstrual cycles (median length 28 days, range 23-44). The urinary LH peak was identified in 228 cycles (97%; median time, day 15 from day 1 of last menses, with range day 10 to day 35). The use of the Rovumeter gave start and end signals of potential fertility during 138 cycles (59%). The median length of the derived PPF was 8 days (range 4-18). The signals covered the defined, minimum PPF in 113 cycles [i.e. 50% of those with an LH peak; range 28% (Milan) to 62% (Birmingham)]. Overall 16/72 women (22%) had successful tests over three consecutive menstrual cycles [range 2/24 (8%; Milan) to 8/23 (35%; Birmingham)]. We conclude that signals from daily changes in the volume of CVF as determined by the use of the Rovumeter consistently locate the minimum period of potential fertility in only a small proportion of women.

1. Incubation of oestrone with ox adrenal glands leads to the formation of two main metabolites, one of which has recently been identified as 15alpha-hydroxyoestrone; the second metabolite (Oe-5) has now been obtained in crystalline form and identified as the hitherto unknown 14alpha-hydroxyoestrone. 2. The identity of compound Oe-5 with 14alpha-hydroxyoestrone was confirmed conclusively by comparison with 14alpha-hydroxyoestrone that was synthesized by pyrolytic aromatization of 14alpha-hydroxyandrosta-1,4-diene-3,17-dione. 3. The physical and chemical properties as well as the oestrogenic activity of 14alpha-hydroxyoestrone are described. 4. The biogenesis and metabolism of 14alpha-hydroxyoestrone were studied in various tissue preparations.

30 postmenopausal patients with metastatic breast cancer were treated with three different doses of fadrozole hydrochloride (CGS 169 49A), a non-steroidal competitive aromatase inhibitor. The effect of 0.5, 1 and 2 mg given twice daily upon the levels of oestrogens, their androgen precursors and upon the concentration of sex hormone binding globulin (SHBG) was investigated after 1 and 3 months and then every 3 months until progression of disease. A significant reduction in the serum concentration of oestrone (P < 0.0001) was obtained at all doses. Also, the serum concentration of oestrone sulphate was significantly reduced (P < 0.0001). However, after 1 month, the concentration was significantly different from pretreatment levels (P < 0.01) only at the 4 mg daily dose. A decline was also observed in the concentration of SHBG (P < 0.05), with a concomitant elevation of the percentage non-SHBG-bound oestradiol. The androgens, testosterone and dehydroepiandrosterone sulphate, were unaltered during treatment, while androstendione was significantly elevated at the 2 mg daily dose (P < 0.001).

The metabolism of various unconjugated oestrogens [oestrone (E1), oestradiol (E2) and oestriol (E3)], in MDA-MB-468 human mammary cancer cells, a cell line characterised by the absence of oestrogen receptor has been investigated. 24 h after incubation of these cells with 5 x 10(-9) mol/l of tritiated E1, E2, or E3, 62-90% of the total radioactivity was localised in the sulphate fraction. Analysis showed that 73-90% of the sulphate fraction corresponds with the oestrogen incubated. The formation of the oestrogen sulphates is rapid and maximum values are found after 3 h incubation. Intense sulphotransferase activity was also found for testosterone, pregnenolone and dehydroepiandrosterone. Thus these cells contained high oestrogen sulphotransferase activity, suggesting that the presence of high levels of oestrogen sulphates in breast cancer can be synthesised in the tumour itself. In addition, the control of this enzymatic activity could open new possibilities in the knowledge of oestrogen responses and of therapeutic applications in breast cancer.

Oestrogen and androgen states have been studied in relation to ovarian morphology defined by ultrasonography in 65 women with oligo-amenorrhoea. Of the 48 women with polycystic ovaries (PCO), 44 (92%) had a withdrawal bleed following progestogen challenge (indicating oestrogenization) compared with just three (18%) of the 17 with non-PCO (P less than 0.001). Median serum concentrations of oestradiol and oestrone were statistically significantly higher in the PCO group but the ranges overlapped widely. Of the four women with PCO but oestrogen deficiency, two were hirsute and had evidence of a severe form of the disorder. The other two were not hirsute and appeared to have hypothalamic dysfunction associated with weight loss overriding the disorder due to pre-existing PCO. Compared with the non-PCO group, the PCO subgroup without hirsutism (n = 31) had statistically significantly higher median values of LH, testosterone, androstenedione, and dehydroepiandrosterone sulphate concentrations, and free androgen index. Concentrations of androgen, but not LH, were significantly higher still in the PCO subgroup with hirsutism (n = 17).

5/10 members of a North African family (father, 2 male and 2 female siblings) had gynaecomastia, early growth and short final stature. The 8-year-old propositus had advanced bone age, facial acne, gynaecomastia, pubic hair and prepubertal testicular volume. Basal oestrone (E1) was elevated (670 pmol/l) and increased with adrenocorticotropic hormone (ACTH; 826 pmol/l). After human chorionic gonadotropin stimulation testosterone (T) responded normally whereas E1 and oestradiol (E2) remained unchanged. ACTH-dependent adrenal feminization was confirmed by a transient reduction of breast tissue following dexamethasone or cypropterone acetate treatment. Testolactone increased T/E2 (from 5.6 to 20.3) and A/E1 (from 3.4 to 31.4) ratios and temporarily reduced the breast tissue. In conclusion, this is a familial type of adrenal feminization with increased adrenal androgen aromatization. This is the first time that male-to-male and male-to-female transmission has been reported.