OBJECTIVE

Traditionally, oestrogens were considered to be protective for the cardiovascular system for premenopausal women. Therefore, we conducted a retrospective case-control study to examine the association between endogenous oestrogens and acute myocardial infarction (AMI) risk among postmenopausal women.

METHODS

A case-control study was performed among 30 primary AMI patients and 60 control subjects. Baseline characteristics data was collected and endogenous sex hormones levels were determined using chemoluminescence and radioimmunoassay methods. Conditional logistic regression models were developed with adjustment for confounders.

RESULTS

Compared with controls, the circulating oestrone, oestradiol, androstenedione and testosterone levels were significantly higher in AMI patients (P < 0.05) while the sex hormone binding globulin (SHBG) level was lower (P < 0.05). Spearman correlation coefficients showed oestradiol was positively correlated with body mass index (BMI) and waist-to-hip ratio (WHR) in cases, but not in controls. In univariable conditional logistic regression models, oestrone, oestradiol, testosterone, WHR, BMI, diabetes and hypertension were all found to be positively associated with AMI (P < 0.05). After adjusting for these factors, oestradiol (odds ratio (OR) = 4.75; 95 % confidence interval (CI) = 1.07-21.10; P = 0.04) and WHR (OR = 6.46; 95 % CI = 1.09-38.39; P = 0.04) continued to demonstrate strong positive associations with AMI.

CONCLUSIONS

A higher level of oestradiol was potentially associated with primary AMI risk among postmenopausal women.

A girl with congenital adrenal hyperplasia due to 21-hydroxylase deficiency could not be controlled by conventional treatment, and was adrenalectomized at age 8.5 years (bone age 13.5 years). After surgery, puberty and menarche occurred. On replacement therapy, her progress was uneventful up to the age of 16 years, when menstruations ceased and signs of virilization reappeared. Testosterone, androstenedione, and 17-hydroxyprogesterone in plasma, and pregnanetriol in urine were high, but DHEA in plasma, and pregnenetriol and pregnanetriolone in urine were low. Oestrogens in plasma were normal. There was no steroid response to ACTH, and marked, but somewhat slow suppression by dexamethasone. HMG induced a strong rise in oestrone and oestradiol. Ethinyloestradiol reduced not only oestradiol in plasma, but also testosterone, androstenedione, and 17-hydroxyprogesterone. With subsequent dexamethasone treatment, menstruation restarted, and the values returned to normal. It is concluded that virilization may reoccur in patients with 21-hydroxylase deficiency even after adrenalectomy, and that the ovaries in this patient contain some tissue, which has properties of adrenal (suppressibility by dexamethasone) and ovarian tissue (suppressibility by ethinyl oestradiol, preference for delta 4-pathway, low steroid 11-oxygenation) at the same time.

In 32 subjects with histologically and/or cytologically verified prostatic cancer the hormonal pattern was studied by assaying 18 plasma and urinary hormones or groups of hormones and relating the values to the response to endocrine treatment. Total orchidectomy (orchiepididymectomy) was performed on 9 patients, subcapsular orchidectomy on 13 patients and oestrogen therapy with Estradurin was given in 4 patients. Six patients had total orchidectomy followed by estrogen therapy. With few exceptions all values were within the normal range. The only significant exceptions were the high urinary oestrogen values and the low urinary oestrone + oestradiol/oestriol ratio observed as compared to healthy males working in a factory. No urinary hormone values or ratios of hormone values could be used for the prediction of prognosis in prostatic carcinoma patients. However, the ratios of plasma testosterone/oestradiol (T/Oe2) and testosterone/prolactin (T/Prl) were found to give good information with regard to the response to endocrine treatment. High values for one or both of these ratios meant a good response to treatment in all subjects without exception in this material. Subjects with both ratios low had a good response to endocrine treatment in 50% of the cases. No other plasma hormones measured were of any help prognostically. It is concluded that by measuring the T/Oe2 and T/Prl ratios it seems possible to select a group of patients with favourable primary response to endocrine treatment.

Sows and ewes were killed at various times during gestation. Minced uterine samples were incubated for 3 h with [6,7-3H]oestrone sulphate or [2,4,6,7-3H]oestrone, respectively. Contrasting patterns of enzyme activities were found in the sow and ewe. In the sow, endometrial sulphotransferase activity declined after Day 30 of gestation, while in the ewe, sulphation gradually increased after Day 16. The inverse was found for the activity of oestrogen sulphatase during pregnancy.

The pharmacokinetics and enterohepatic cycling of oestradiol have been studied after three oral, single-dose administrations of equimolar doses of oestradiol alone, oestradiol plus desogestrel and oestradiol valerate, in a 3-way cross-over mode in 18 healthy postmenopausal women. Oestradiol was readily absorbed and metabolized to oestrone, which reached much higher serum concentrations (140pgmL(-1)) than its parent compound (35pgmL(-1)). All three formulations had the same kinetic profile and were bioequivalent on testing. Noticeable first and second absorption phases were apparent from the oestradiol and oestrone serum concentration-time curves for all oestradiol formulations. The mean serum concentration-time curves of the metabolite oestrone (corrected for endogenous oestrone) showed a second maximum at approximately 25h. By means of line feathering, serum concentration-time curves were constructed which belonged to the first, second and third phases of absorption. The maximum serum concentration, Cmax, of the second absorption or recirculation of oestrone was 20% that of the first, and the Cmax of the third circulation was 50% that of the second. The areas under the serum-concentration-time curves (AUC) for the second and third recirculations were similar-each comprised 12-13% of the total AUC. The oral clearance values of the recirculations were constant (590Lh(-1)). Enterohepatic recirculation of endogenous compounds is aimed at maintaining a steady-state serum concentration for immediate use and hydrolysis in the target organs. It is concluded that exogenously added oestradiol and its metabolites follow the recirculation pathways of the endogenous oestrogen pool.

Evidence from two groups of post-menopausal women who were randomly allocated to be treated with either conjugated equine oestrogens or piperazine oestrone sulphate demonstrates that the two oestrogens produce markedly different effects on blood pressure. The conjugated equine oestrogens appear to produce no significant change in either systolic or diastolic blood pressure whereas piperazine oestrone sulphate produced a significant fall in both systolic and diastolic blood pressure. This finding is discussed in relationship to the known causes for a change in cardiovascular response to oestrogen and several hypotheses are put forward.

1. The separation of the oestrogen conjugates in late-pregnancy urine into two groups, peaks I and II, by gel filtration on Sephadex G-25 (Beling, 1963) has been shown to be affected by the presence of urate, which delays the elution of peak II conjugates. 2. By reapplication to a Sephadex column, peak I conjugates have been further separated into two groups (peaks IA and IB) and the metabolites in urine effecting this separation have been studied. 3. Further analysis of the mixed conjugates in the main groups IA, IB and II by ion-exchange and partition chromatography has led to the identification of some of the conjugates present. 4. Oestriol 3-sulphate 16alpha-glucuronide and 16alpha-hydroxyoestrone 3-sulphate 16alpha-glucuronide have been identified in peak IA. 5. The main components of peak IB have been identified as oestrone 3-glucuronide and oestriol 3-glucuronide. 6. The major conjugate in peak II was oestriol 16alpha-glucuronide and no oestriol 17beta-glucuronide was found; small amounts of the ring-d monoglucuronides oestradiol 17beta-glucuronide, 16-epioestriol 16beta-glucuronide and 16alpha-hydroxyoestrone 16alpha-glucuronide were found in this fraction. 7. The behaviour of synthetic oestrogen monoglucuronides has been used as a guide in separation.

The aim of this study was to determine the impact of the administration route and cigarette smoking on plasma oestrogen levels during oral and parenteral oestrogen replacement therapy (ERT). Fourteen healthy postmenopausal women (six smokers and eight non-smokers) were recruited for a prospective, randomised, crossover study at a private outpatient medical centre in Oslo, Norway. All patients were randomised to receive cyclic therapy with oestradiol and norethisterone orally or by the transdermal route each for a 6-month period. Plasma levels of oestrone (Oe(1)), oestradiol (Oe(2)) and oestrone sulphate (Oe(1)S) were determined using highly sensitive RIA methods before and during hormone replacement therapy given by the oral and transdermal route. Comparing smokers and non-smokers, plasma levels of Oe(1), Oe(2) and Oe(1)S were all found to be 40-70% lower in smokers compared with non-smokers when ERT was given orally (Oe(1)S, P<0.05; Oe(1) and Oe(2), P<0.01 for both). Oe(2) given orally caused a higher Oe(1)S/Oe(2) ratio but also a higher Oe(1)/Oe(2) ratio compared with parenteral therapy in smokers (40.2 versus 7(.)0, P<0.01; and 3.2 versus 0.8, P<0.05 respectively). No significant differences in these parameters in the different test-situations were seen in non-smokers. Except for a lower level of Oe(1)S in smokers (non-significant), no difference in plasma oestrogen levels between smokers and non-smokers was observed during parenteral therapy. In conclusion, cigarette smoking has been shown to have major impact on plasma oestrogen levels during oral but not during parenteral Oe(2) replacement.

Conjugated and unconjugated oestrone, oestradiol and oestriol were measured in simultaneous milk and plasma samples obtained from 21 women in the early post-partum period. Conjugated oestrogens comprised more than 90% of the total oestrogen content of both milk and plasma. Oestrone glucosiduronate was the major oestrogen metabolite in milk (33%), the levels being significantly higher (P less than 0.01) than in plasma. Oestriol glucosiduronates were the predominant oestrogen metabolites (63%) in plasma.

Intraperitoneal administration of sodium oestrone [(35)S]sulphate to male and female free-ranging guinea pigs is followed by excretion of most of the radioactivity mainly as inorganic [(35)S]sulphate in the urine within 72h. The remainder of the radioactivity in the urine was found in oestrone [(35)S]sulphate, two unidentified metabolites (A and B) and traces of oestradiol-17beta 3-[(35)S]sulphate. When injected intraperitoneally into animals with bile-duct and bladder cannulae, most of the dose was excreted in the bile. Unchanged oestrone [(35)S]sulphate was the main biliary component excreted in males and females, but the latter also excreted appreciable amounts of oestradiol-17beta 3-[(35)S]sulphate and metabolites A and B. The urine from these animals also contained these metabolites, inorganic [(35)S]sulphate and also oestrone [(35)S]sulphate, but in small amounts. Metabolite A was present only in samples from males. Whole body radioautography pinpointed the liver and kidney as the possible sites of metabolism of the ester. The ester underwent little desulphation in the isolated perfused female guinea-pig liver and in animals in which kidney function had been eliminated, and was excreted unchanged in the bile. These results and the observed low oestrogen sulphatase and arylsulphatase C activities found in guinea-pig liver and kidney support the view that the two enzymes are identical.

OBJECTIVE

Oestrogens can interact directly with membrane receptors and channels and can activate vascular BK(Ca) channels. We hypothesized that novel oestrogen derivatives could relax smooth muscle by an extracllular effect on the α and β1 subunits of the BK(Ca) channel, rather than at an intracellular site.

METHODS

We studied the effects of novel oestrogens on the tension of pre-contracted isolated rat aortic rings, and on the electrophysiological properties of HEK 293 cells expressing the hSloα or hSloα+β1 subunits. Two of the derivatives incorporated a quaternary ammonium side-chain making them membrane impermeable.

RESULTS

Oestrone, oestrone oxime and Quat DME-oestradiol relaxed pre-contracted rat aorta, but only Quat DME-oestradiol-induced relaxation was iberiotoxin sensitive. However, only potassium currents recorded in HEK 293 cells over-expressing both hSloα and hSloβ1 were activated by oestrone, oestrone oxime and Quat DME-oestradiol.

CONCLUSIONS

The novel oestrogens were able to relax smooth muscle, but through different mechanisms. In particular, oestrone oxime required the presence of the endothelium to exert much of its effect, whilst Quat DME-oestradiol depended both on NO and BK(Ca) channel activation. The activation of BK(Ca) currents in HEK 293 cells expressing hSloα+β1 by Quat DME-oestradiol is consistent with an extracellular binding site between the two subunits. The binding site resides between the extracellular N terminal of the α subunit and the extracellular loop between TM1 and 2 of the β1 subunit. Membrane-impermeant Quat DME-oestradiol lacks an exchangeable hydrogen on the A ring obviating antioxidant activity.

Ovarian or uterine lymph was collected continuously for periods of up to 25 days from 16 cows cannulated at stages of pregnancy ranging from 96 to 278 days post coitum. Blood samples were taken acutely from the ovarian and uterine veins during surgery and periodically from the jugular vein during the course of lymph collection. The flow rate and cell content of lymph was measured and blood and lymph plasma samples were analysed for progesterone, pregnenolone, pregnenolone sulphate, androstenedione, testosterone, oestrone, oestrone sulphate, oestradiol-17 beta, prostaglandin (PG) F-2 alpha, total protein and albumin. There was a high flow rate of protein-rich lymph from luteal ovaries with rates up to 101.7 ml/h occurring in individual lymphatics over short periods. Peripheral ovarian and uterine lymph contained a low concentration of cells (mean less than 10(5) cells/ml) comprising about 82-87% lymphocytes, 11-14% macrophages and monocytes and 2-4% other cells. At all stages of pregnancy, the concentration of progestagens and androgens was higher in ovarian lymph than in uterine lymph or blood plasma. The differences were greatest for progesterone and androstenedione which occurred at 200-fold and 60-fold greater concentration respectively in ovarian lymph than in jugular plasma. When serial 10 min samples were collected over a 12-h period, the concentration and output of progesterone in ovarian lymph varied in a phasic manner, ranging from 3.5 to 7.6 microM and from 31.7 to 293.1 nmol/h respectively. There was a positive correlation between the output of progesterone in lymph and the progesterone concentration in jugular blood samples taken every 20 min. During most of pregnancy there was little difference between the concentration of oestrogens in ovarian lymph, ovarian venous plasma and jugular plasma but, during the 3-5 days before calving, these hormones occurred at slightly higher concentration in ovarian lymph. Apart from pregnenolone and androstenedione, all steroids occurred at lower concentrations in uterine lymph than in jugular plasma. Shortly before parturition there was an abrupt increase in the concentration of PGF-2 alpha in uterine lymph. Lymph reflects more accurately the milieu of tissue cells than efferent blood and further analysis of differences in the concentration of substances in lymph relative to the output in the ovarian and uterine arterial and venous blood may lead to the identification of factors important in local regulatory mechanisms in the reproductive tract.

1. Cortisol treatment of rabbit foetuses in utero at 24 days gestation produced a significant decrease in the lung-weight to body-weight ratio compared with littermate controls by day 26. Histological examination revealed that the alveoli of the treated lungs were more open, the walls were thinner and the osmiophilic bodies were more numerous. 2. Cortisol treatment as described above produced significant increases (P<0.05) in the rates of incorporation of [(14)C]choline into phosphatidylcholine and of [(14)C]ethanolamine into phosphatidylethanolamine in vitro compared with littermate controls. This indicates that glucocorticoids produce an overall increase in phospholipid metabolism rather than a specific increase in phosphatidylcholine production. 3. The addition of 1,2-diacyl-sn-glycerols from egg phosphatidylcholine produced a 10-fold increase in the activity of choline phosphotransferase and a 3-fold increase in the activity of ethanolamine phosphotransferase in rabbit lung homogenates. The addition of 1,2-dipalmitoyl-sn-glycerol did not affect these activities. These results demonstrate that in the presence of exogenous 1,2-dipalmitoyl-sn-glycerol, the activities of these enzymes are dependent on the presence of endogenous 1,2-diacylglycerols. 4. Cortisol administration had no significant effect on the activity of choline phosphotransferase or ethanolamine phosphotransferase with endogenous or exogenously added diacylglycerols. The activities of other endoplasmic-reticulum enzymes (sn-glycerol 3-phosphate phosphatidyltransferase, sn-glycerol 3-phosphate acyltransferase and NADPH-cytochrome c reductase) were not significantly altered by the hormone administration. Oestrone sulphate sulphohydrolase activity was significantly decreased (P<0.05) by cortisol injection, but this effect varied with the foetuses from different does. 5. Cortisol administration had no effect on the activities of mitochondrial (monoamine oxidase, succinate dehydrogenase), plasma-membrane (5'-nucleotidase) or lysosomal (acid phosphatase, N-acetyl-beta-d-glucosaminidase) enzymes. The activity of membrane-associated phosphatidate phosphohydrolase, an enzyme associated with the osmiophilic granules of the type-II alveolar cells, was increased in the lungs of treated foetuses, but the difference was not significant (0.10>P>0.05).

Oestrogen is important in the development of breast cancer. Oestrogen receptor positive breast cancers are associated with a better prognosis than oestrogen-receptor negative breast cancers since they are more responsive to hormonal treatment. Oestrone sulphate acts as a huge reservoir for oestrogens in the breast. It is converted to the potent oestrogen, oestradiol (E(2)) by the enzymes oestrone sulphatase and oestradiol-17beta hydroxysteroid dehydrogenase (E(2)DH). Retinoic acid and carotenoids have been shown to have chemopreventive activity against some cancers. The aim of our study was to determine and compare the effects of retinoic acid and palm oil carotenoids on growth of and oestrone sulphatase and E(2)DH activities in the oestrogen receptor positive, MCF-7 and oestrogen receptor negative, MDA-MB-231 breast cancer cell lines. Retinoic acid and carotenoids inhibited MCF-7 cell growth but had no effect on MDA-MB-231 cell growth. Both retinoic acid and carotenoids stimulated oestrone sulphatase activity in the MCF-7 cell line. E(1) to E(2) conversion was inhibited by 10(-7) M carotenoids but was stimulated at 10(-6) M in the MCF-7 cell line. Retinoic acid had no effect on E(1) to E(2) conversion at 10(-7) M but stimulated E(1) to E(2) conversion at 10(-6) M. Retinoic acid and carotenoids had no effect on E(2) to E(1) conversion in the MCF-7 cell line. Retinoic acid stimulated E(1) to E(2) conversion in the MDA-MB-231 cell line but had no effect on oestrone sulphatase activity or E(2) to E(1) conversion in this cell line. Both oestrone sulphatase and E(2)DH activity were not affected by carotenoids in the MDA-MB-231 cell line. In conclusion, retinoic acid and carotenoids may prevent the development of hormone-dependent breast cancers since they inhibit the growth of the MCF-7 cell line.

Short or long term alloxan diabetes produced activation of oestrone and morphine glucuronidation and inhibition of p-nitrophenol glucuronidation in rat liver microsomes. Insulin treatment restored decreased glucuronyltransferase (GT) activity for p-nitrophenol and it did not abolish diabetes activation on oestrone glucuronidation. Triton X-100 detergent activation reduced differences between normal, diabetic and insulin treated rats in the glucuronidation rates of the substrates assayed. 1,4-Benzodiazepines inhibited morphine GT activity and stimulated oestrone GT activity in normal, diabetic and insulin treated diabetic rats. Activation and inhibition of GT activities for oestrone and xenobiotics in diabetes mellitus appears to be related with membrane perturbations of liver microsomes.

A variety of clinical and experimental evidence indicates that the oestrogens are the major hormones affecting human breast cancer growth. The goal of recent treatment strategies is to reduce the amount of oestradiol acting locally on the tumour. For this reason, it is relevant to examine what determines tumour tissue oestradiol concentrations. Various steps are potentially important and include glandular or extraglandular production of oestradiol, tissue uptake, binding to receptors and the rate of local tissue oestradiol synthesis. In premenopausal women, glandular secretion of oestradiol by the ovary provides the major source of tissue oestradiol. In postmenopausal women, the extraglandular conversion of androstenedione to oestrone and then oestradiol in peripheral tissues accounts for 90% of circulating oestradiol. However, plasma levels of oestradiol in postmenopausal women are only 4 to 40% of those found in premenopausal patients and yet breast cancer tissue levels are similar. This observation suggests the possibility of local oestradiol synthesis by breast tumours in postmenopausal women. We examined two pathways which could be involved in local oestradiol synthesis: the androstenedione to oestrone (aromatase) pathway and the oestrone-sulphate to oestrone (sulphatase) system. Seventy-nine of 128 tumours contained aromatase with activity ranging from 5-80 pmol/g protein/hr. This enzyme was of high affinity with a Km of 0.027 microM. Sulphatase, on the other hand, was present in all tumours with activity ranging from 0.8-125 microM. Its affinity was appreciably lower with a Km of 27 microM. Comparing both activities at substrate concentrations approaching physiological levels, we detected 10-fold higher activity with sulphatase than with aromatase. Further studies revealed the presence of 17 beta-hydroxysteroid dehydrogenase in all tumors studied. Whereas 50% of tissues contained both a high and a low affinity type of activity, the remainder had only the low activity form. Since our data favoured the oestrone-sulphate to oestrone to oestradiol pathway as biologically relevant, we sought to determine whether oestrone-sulphate could act as an oestrogen after conversion to oestradiol. Using an NMU rat mammary tumour soft agar colony forming assay, we found that oestrone-sulphate stimulated colony growth in a manner consistent with its 1% conversion to oestradiol by cells in the agar dishes. Furthermore, preliminary data indicate that oestrone-sulphate can stimulate NMU tumour growth in vivo in rats. The metabolism of oestradiol in tissue can also determine its biological effects and its tissue levels.(ABSTRACT TRUNCATED AT 400 WORDS)

A progestogen (norethisterone) and a dopamine antagonist (sulpiride) were given alone and in combination to volunteers to examine their effects on excretion of ovarian steroids. Compared with non-treatment cycles (n = 15), contraception with a progestogen alone (n = 10) was associated with increased excretion of oestrone and partial suppression of excretion of pregnanediol, suggesting partial luteinization of unruptured follicles. By contrast, the combination of norethisterone and sulpiride (n = 9) suppressed both ovarian steroids to basal values, the suppression being even greater than with sulpiride alone (n = 5). These results suggest that a combination of a progestogen with a dopamine antagonist might have a role in contraception.

The cytochrome P450 responsible for androgen synthesis by the placenta during the second half of pregnancy in the rat was studied in intact and hypophysectomized animals. The two activities of P450(17) alpha, 17 alpha-hydroxylase and C17,20-lyase, were limited to the junctional zone. C17,20-Lyase activity was greater with progesterone than with 17-hydroxyprogesterone as substrate. Although the apparent Michaelis constants were similar, progesterone had a higher maximum velocity than 17-hydroxyprogesterone. Regardless of substrate, C17,20-lyase activity was greater with NADPH than with NADH as an electron donor, and there was no additive effect using both cofactors. Administration of human chorionic gonadotrophin (hCG; 10 IU at 09.00 and 21.00 h on days 13 and 14 and at 09.00 h on day 15) to intact females resulted in more than a 50% reduction of enzyme activity when measured on day 15. The same dose of hCG given to hypophysectomized animals with delayed implantation, i.e. pituitary removal on day 3 and implantation induced by oestrone 5 days later, had no effect on placental enzyme activity, but increased that in the ovary. Administration of ovine LH by osmotic minipump (days 11-15) to intact females resulted in abortion in all animals. The same treatment to animals hypophysectomized on day 11 produced abortion in three of four rats; enzyme activity was greatly reduced in the single animal with placentas. In contrast, infusion of LH into hypophysectomized animals with delayed implantation increased placental enzyme activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Between Days 9 and 15 after oestrus, concentrations of pregnenolone, pregnenolone sulphate, dehydroepiandrosterone (DHEA), DHEA sulphate, androstenedione, oestrone and oestrone sulphate in free uterine fluid collected from non-pregnant gilts were greater than respective values in plasma (P less than 0.05). The total contents of pregnenolone, progesterone, DHEA, testosterone, oestrone and oestradiol in washings from pregnant uteri exceeded (P less than 0.05) respective non-pregnancy levels during this same period. Concentrations of pregnenolone, pregnenolone sulphate, DHEA, DHEA sulphate, androstenedione, oestrone, oestrone sulphate and oestradiol in free uterine fluid recovered from gravid uteri were also higher (P less than 0.05) than respective plasma values. By contrast, the progesterone concentration in uterine fluid from pregnant animals was lower (P less than 0.001) than the plasma value. Concentrations of DHEA, DHEA sulphate, androstenedione and oestrone sulphate in plasma of pregnant gilts between Days 9 and 15 after mating exceeded (P less than 0.05) the respective concentrations in unmated gilts between Days 9 and 15 after oestrus. Plasma levels of pregnenolone sulphate were lower (P less than 0.05) in the pregnant animals. We therefore suggest that the endometrium of the pig can concentrate steroid hormones in uterine fluid and that increases in steroid levels in this milieu between Days 9 and 15 after coitus reflect steroidogenesis by embryonic tissues and modification of enzyme activities within uterine tissues under the influence of progestagens. The pool of steroid sulphoconjugates present in uterine fluid between Days 9 and 15 post coitum could serve as an important precursor source for progestagen, androgen and oestrogen synthesis by tissues of pig embryos before implantation.

The concentration of prostaglandin F2alpha (PGF2alpha), progesterone, pregnenolone, oestradiol-17beta, oestrone, androstenedione and testosterone was measured in corpora lutea obtained from 40 women at various stages of the menstrual cycle. The concentration of PGF2alpha was significantly higher in corpora lutea immediately after ovulation (26-7 +/- 3-9 (S.E.M.) ng/g, P less than 0-005) and in corpora albicantia (16-3 +/- 3-3 ng/g, P less than 0-005) than at any other time during the luteal phase. There was no correlation between the concentration of PGF2alpha, and that of any steroid. The progesterone concentration was highest in corpora lutea just after ovulation (24-9 +/-6-7 microng/g) and in early luteal groups (25-7 +/- 6-8 microng/g) but declined significantly (P less than 0-05) to its lowest level in corpora albicantia (1-82 +/- 0-66 microng/g). The concentration of oestradiol-17beta in the corpus luteum and luteal weight were significantly greater during the mid-luteal phase than at any other stage (concentration 282 +/- 43 ng/g), P less than 0-05; weight 1-86 +/- 0-18 g, P less than 0-005). The results indicate that regression of the human corpus luteum is not caused by a rise in the ovarian concentration of PGF2alpha in the late luteal phase of the cycle.

Circulating progesterone, oestrogens and LH were measured in female marmosets (Callithrix jacchus) over the periovulatory period. Progesterone concentrations increased in all animals within 1 day of the estimated day of ovulation, confirming the usefulness of this hormone for retrospective detection of ovulation. Oestradiol-17 beta and LH both showed a preovulatory rise, but due to the large quantity of plasma required (oestradiol: 0.2 ml) and the length of time taken for the assay (LH: 2-3 days), measurement of these hormones is not practical for the prediction of ovulation. There were no preovulatory changes in unconjugated oestrone, but a rise in total (i.e. conjugated plus unconjugated) oestrone was used to time the collection of recently ovulated oocytes. Levels of oestrone-3-sulphate showed an increase at least 1 day before the expected day of ovulation in four out of five animals. This preovulatory rise can be measured easily by a rapid direct assay, thereby providing a practical method for predicting ovulation in this species.