Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma.

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.

Childhood adversities and risk of posttraumatic stress disorder and major depression following a motor vehicle collision in adulthood.

AIMS: Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions. METHODS: Data came from n = 999 patients ages 18-75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models. RESULTS: Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31-1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65-2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43-2.87) and bullying (RR = 1.44; 95% CI = 0.99-2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE. CONCLUSIONS: Although individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.

A specific radioimmunoassay for estrone sulfate in plasma and urine without hydrolysis.

Estrone sulfate, quantitatively the most important estrogen in plasma, has previously been determined only after hydrolysis and chromatography. An antiserum raised against estrone glucosiduronate-bovine thyroglobulin was found to be suitable for the specific RIA of estrone sulfate both in plasma and urine. Plasma levels were measured after solvent extraction without hydrolysis or chromatography. The mean (+/-SE) was 972 +/- 79 pg/ml (range, 537-1581) in 15 women in the follicular phase, 1806 +/- 160 pg/ml (range, 814-3358) in 15 women in the luteal phase, and 922 +/- 62 pg/ml (range, 461-1238) in 13 men. The urinary excretion of estrone sulfate, measured after simple chromatographic separation, ranged from 0.8-7.9 micrograms/24 h in men and 5.1-18.7 micrograms/24h in nonpregnant women. This was generally one-seventh to one-half the simultaneous estrone glucosiduronate excretion rate. An approximate mean renal clearance of estrone sulfate calculated from the above values was 2.7 ml/min. The low clearance rate is taken to reflect extensive binding of estrone sulfate by plasma proteins. The splanchnic extraction of estrone sulfate measured in 6 patients undergoing hepatic vein catheterization for diagnostic purposes was 29.8 +/- 11.1%, indicating net uptake of this compound by the splanchnic area.

Effect of diet on oxidation of 17 beta-estradiol in vivo.

The effect of a high fat, low carbohydrate, low protein diet on the in vivo oxidation of 17 beta-estradiol was studied using radiometric methods. Five male chimpanzees were fed a normal (13%) fat diet or a high (65%) fat diet for 8 weeks. After a 4-week rest period, the animals were fed the alternative diet. The mean percent oxidation of 16 alpha-[3H]estradiol-17 beta 24 h after injection was 3.8 +/- 1.3% (+/- SD) on the normal diet vs. 18.4 +/- 4.7% on the high fat diet (P less than 0.01). In contrast, the mean percent oxidation of 2-[3H]estradiol 24 h after injection was 31.6 +/- 3.8% (+/- SD) on the normal diet vs. 20.0 +/- 3.5% on the high fat diet (P less than 0.05). These results suggest that the oxidation of 17 beta-estradiol to estriols relative to that to catechol estrogens is increased by a high fat diet.

Hormonal profiles of natural conception cycles ending in early, unrecognized pregnancy loss.

Loss of a conceptus early in development can be detected by very sensitive assays specific for hCG. We examined 20 menstrual cycles ending in early loss of a conceptus in order to identify hormonal correlates of loss. Each loss cycle was compared to a successful conception cycle in the same woman, using daily concentration of urinary estrone-3-glucuronide and pregnanediol-3-glucuronide (PdG). The estrone-3-glucuronide and PdG profiles in cycles of early pregnancy loss were very similar to those in successful conception cycles until late in the luteal phase. Early pregnancy loss was not related to a midluteal deficiency in PdG. hCG tended to be detected later in cycles of early pregnancy loss than in successful conception cycles, presumably indicating later implantation. Ten of the early pregnancy losses implanted after luteal-day-10; only one of the successful pregnancies implanted that late. The corpus luteum responded to the conception in only 2 of the 10 loss cycles with late implantation. In contrast, the corpus luteum responded in 8 of 10 loss cycles with normally timed implantation. The similarity of preimplantation hormonal profiles in cycles of early pregnancy loss and in cycles with successful conceptions suggests that most early losses in reproductively normal women do not result directly from deficiencies in ovarian steroid production.

Long term effects of a first pregnancy on the hormonal environment: estrogens and androgens.

An early (but not a late) first pregnancy is known to be protective for breast cancer. This effect might be mediated through a long term change in the hormonal environment caused by the early first pregnancy. To investigate the possibility of such a change we carried out a prospective longitudinal study of serum and urinary estrogens and serum androgens in four groups of women, namely early (age, 18-23 yr) first pregnancy (n = 15), early control (n = 20), late (age, 29-40 yr) first pregnancy (n = 9), and late control (n = 20). The pregnancy groups were studied before (initial visit) and 7-19 months after a first pregnancy (return visit). The control groups were similarly studied, but without an intervening pregnancy. The following were measured: serum estrone (E1), 17 beta-estradiol (E2), estriol (E3), and E1 sulfate; urinary total E1, E2, E3, and glucosiduronates of these three estrogens; and serum testosterone, dehydroepiandrosterone sulfate (DHAS), and dehydroepiandrosterone (DHA). There was no significant change between the initial and return visits in serum E1, E2, E1 sulfate, or any of the urinary estrogens in either pregnancy group or in the corresponding control groups. There was, however, a significant increase in serum E3 between initial and return visits for both pregnancy groups compared with the control values. There was no significant change in serum testosterone. There was a marked significant decrease in both serum DHAS and DHA between initial and return visits in both pregnancy groups compared with the corresponding control group values. There was also a significant increase in the serum E3 to DHA ratio in both pregnancy groups. A cross-sectional study (measuring serum DHAS and DHA only) was then carried out in a series of parous and nulliparous women. The serum DHAS and DHA levels were markedly and significantly lower in parous than in nulliparous women, as expected. There was no significant relationship between serum DHAS or DHA levels and months elapsed (up to 150) since last delivery, indicating that the changes last at least for this period of time. There was no significant relationship between serum DHAS or DHA levels and parity (one to three previous pregnancies), indicating that the changes occur only after a first pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS)

The use of biochemical assays in epidemiologic studies of reproduction.

Recent progress in the assay of urinary hormones has opened new opportunities for epidemiologists to study hormones and health outcomes. This is especially true for studies of female reproduction. The cyclic nature of female reproduction can be fully described only by continuous frequent measurements that, in order to be practical, require easily collected biological specimens. We describe our experience in collecting and analyzing daily urine specimens from 301 healthy women. We conclude that this approach is not only feasible but potentially of great value to epidemiologists for studying fertility, early pregnancy, the effects of toxic exposures on reproduction, and the relationships between reproduction and later risk of chronic diseases.

The relationship of exercise to anovulatory cycles in female athletes: hormonal and physical characteristics.

The objective of this study was to examine the mechanisms by which physical activity affects the menstrual cycle. Women with high, medium, and low levels of physical activity were compared for menstrual function, physical characteristics, and urinary and serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, estradiol-17 beta, and 2-hydroxyestrone. None of the physical characteristics other than age and muscle area were significantly different in the three groups. The percentage of body fat did not appear to be a factor in the amenorrhea induced by strenuous exercise, as the percent of body fat in all three groups was less than 22%. The group of athletes under strenuous exercise which correlated with oligomenorrhea had decreased serum levels of luteinizing hormone, prolactin, and estradiol-17 beta but elevated levels of 2-hydroxyestrone. These data suggest that anovulatory cycles are correlated with the amount of exercise and increased levels of catechol estrogens. Catecholamines and beta-endorphin elevated by exercise may interact to suppress luteinizing hormone release at the hypothalamic pituitary axis.

The role of beta-endorphins and catechol estrogens on the hypothalamic-pituitary axis in female athletes.

Competitive swimmers were followed over a 2-year period when they trained at different levels of exercise which coincided with distinct changes in their menstrual history. Oligomenorrhea was identified in 5 of 13 of these athletes when they swam approximately 100,000 yards per week. Weight and percentage of body fat were not significantly different between the period of oligomenorrhea and regular menstrual function (P = 0.24). Mean and median levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and 17beta-estradiol were decreased and catechol estrogens and beta-endorphins were increased in serum during the strenuous, when compared with the moderate, training period. The serum levels of the steroid and protein hormones were similar to those of normal cycling, nonexercising control subjects during moderate exercise (60,000 yards per week). The significant differences between beta-endorphins and catechol estrogens during periods of strenuous exercise suggest an explanation for oligomenorrhea in female athletes. These hormonal changes result in hypothalamic anovulation, which appears to be reversible, because the hormone levels and menstrual cycles return to normal when the exercise is reduced.

Identification of lignans and phytoestrogens in urine of chimpanzees.

It was recently observed that the urinary excretion of animal lignans is low in postmenopausal breast cancer patients compared to normal omnivorous and vegetarian women. In addition, the mean excretion of the isoflavonic phytoestrogen equol tended to be lower. Because nonhuman primates appear to be remarkably resistant to the carcinogenic effect of estrogens, we investigated the possible occurrence of lignans and phytoestrogens in the urine of chimpanzees on their regular diet. Five major diphenols were isolated and identified by capillary gas chromatography and mass spectrometry by comparison with synthesized authentic reference compounds. Three of these compounds, the phytoestrogen equol and its precursor daidzein, the lignan enterolactone, were according to preliminary assays excreted in very large amounts. In addition, the lignan enterodiol and the daidzein metabolite O-desmethylangolensin were identified. It is concluded that the chimpanzee excretes both isoflavonic phytoestrogens and lignans in urine, apparently in high concentrations. It is suggested that these compounds may play a role in the maintenance of the resistance against carcinogenic effects of estrogens, which nonhuman primates possess, because both equol and enterolactone have been shown to have antiestrogenic properties in animals. However, much further work is necessary before the possible biological role of these compounds may be established.

Depletion of essential elements by calcium disodium EDTA treatment in the dog.

The effect(s) of calcium disodium ethylenediaminetetraacetate (CaNa2EDTA) on the metabolism of Zn, Cu and Mn was investigated in mongrel female dogs. Dogs received either CaNa2EDTA (0.75 mmol/kg subcutaneously) or 0.9% NaCl (controls). Urine was collected every 6 h. Tissue samples were obtained from liver, kidney, duodenum, muscle, hair, skin and bone post exsanguination. CaNa2EDTA treatment increased urinary excretion of Zn, Cu and Mn, significantly when compared to controls (P less than 0.05, n = 5). Furthermore, CaNa2EDTA either decreased Zn levels (hair, duodenum, skin) and Mn levels (hair) or increased Cu levels in kidneys (P less than 0.05). These data suggest that the sustained urinary loss of Zn, Cu and Mn was probably associated, in part, with mobilization and redistribution of these essential elements from storage tissues as well as soft tissues. It was concluded that the use of calcium disodium EDTA for the management of heavy metal poisoning in dogs could adversely affect the metabolism of essential elements, particularly Zn, Cu and Mn.

Modulation of hepatic glucose-6-phosphate dehydrogenase activity in male and female rats by estrogen.

The effect of estradiol-17 beta on the activity of glucose-6-phosphate dehydrogenase was studied in both male and female rats to further characterize the sex differences in the activity of this enzyme. Four groups of intact and castrated rats were implanted subcutaneously with graded doses (2.4, 4.8 and 7.2 micrograms/day) of pelleted estradiol in a physiologically relevant experimental system. After fourteen days the rats were sacrificed and their livers were assayed for G6PD activities. The result indicated that: (i) the enzyme activity was 3-fold higher in normal adult female than in male rats, (ii) low doses of E2 (2.4, 4.8 and 7.2 micrograms/day) increased the activity of G6PD 6-fold in castrated males and over 2-fold in female castrates as well as intact rats (iii) E2 stimulation of G6PD activity appears to be more effective in castrated males than in female rats (IV) sex difference in the activity of G6PD disappeared after treatment with E2 in castrated rats. It is concluded that the activity of G6PD in rats is markedly enhanced by low doses of E2, which appears to be largely responsible for the sex differences in the activity of this enzyme in rats.

Effect of diet on lignans and isoflavonoid phytoestrogens in chimpanzees.

Diphenolic compounds belonging to the classes of lignans and isoflavonoids have been identified in urine of man and animals, including the chimpanzee. Some of these compounds, formed by intestinal bacteria from plant lignans and phytoestrogens, have been shown in animal studies to exhibit biological activities that suggest they could function as cancer-protective compounds. The effect of diet on urinary excretion of these compounds in the adult male chimpanzee has been studied. It was found that the chimpanzees consuming their regular food excreted large amounts of the isoflavonoid phytoestrogens, equol (mean +/- SE) (127.5 +/- 34.0 nmol/mg cr.) and daidzein (20.7 +/- 9.0 nmol/mg cr.) and the lignan, enterolactone (14.1 + 3.5 nmol/mg cr.). Small amounts of the lignan, enterodiol, (0.4 +/- 0.2 nmol/mg cr.) were also excreted. On all other four test diets (high protein, high carbohydrate, high vegetable, and high fat), the excretion was less, particularly on a high fat diet where the excretion of all diphenolic compounds was reduced by more than 90% to a level observed in omnivorous human subjects or women with breast cancer. These results suggest that diet profoundly influences the excretion of both animal lignans and phytoestrogens in urine. Because non-human primates are particularly resistant to mammary and genital carcinoma on estrogen treatment, the present data suggest that the very high levels of phytoestrogens and lignans as found during exposure to the regular diet may partially account for why these primates are so resistant to hormonal manipulations to induce cancer.

Direct radioimmunoassay of specific urinary estrogen glucosiduronates in normal men and nonpregnant women.

Direct radioimmunoassay are described for the measurement of each of three specific estrogen glucosiduronates: estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate and estriol-16 alpha-glucosiduronate in urine. Each assay utilizes a specific antiserum prepared by complexing the carboxylic acid group of the appropriate glucosiduronate to the epsilon-amino group of lysine in bovine serum albumin or bovine thyroglobulin. The antisera showed little or no cross reactivity toward other estrogens that might be present in significant amounts in urine. These antisera were used for the direct assay of the conjugates in urine from normal men and nonpregnant women without prior extraction or chromatography. The values were similar to those obtained after extraction, chromatographic purification on DEAE-Sephadex and subsequent immunoassay; The following mean values +/- SE (microgram/g creatinine) were obtained: estrone glucosiduronate, male 10.1 +/- 0.6, follicular phase female 17.3+/- 1.6, luteal phase female 31.8 +/- 2.5; 17 beta-estradiol-17-glucosiduronate, male 1.7 +/- 0.3, follicular phase female 2.4 +/- 0.1, luteal phase female 4.2 +/- 0.4; estriol-16 alpha-glucosiduronate, male 1.8 +/- 0.2, follicular phase female 4.7 +/- 0.9, luteal phase female 10.0 +/- 1.6.

Separation of estrogen conjugates by high pressure liquid chromatography.

High pressure liquid chromatography using a prepacked commercial strong anion exchanger column (mu Partisil 10 SAX, 25 cm x 4.6 mm) was used to separate a mixture of eight estrogen conjugates. Chromatographic conditions using a 0.01 M potassium phosphate or 0.1 M NaCl as solvent in the isocratic mode are described for the separation of estrone glucosiduronate, 17beta-estradiol-3-glucosiduronate, 17beta-estradiol-17-glucosiduronate, estriol-3-glucosiduronate, estriol-16alpha-glucosiduronate, estriol-17-glucosiduronate, estrone sulfate and 17beta-estradiol-3-sulfate. This system gives high resolution of the estrogen conjugates in small eluent volumes in less than 30 min. The advantages of this high pressure liquid chromatographic system over other methods of separation are discussed.

In vitro biosynthesis of radioactive estradiol-17 beta, 17-glucosiduronate by rhesus monkey liver.

A method for the preparation of radioactive estradiol-17 beta, 17-glucosiduronate by incubating 3H-estradiol with rhesus monkey liver microsomal preparation in the presence of uridine diphosphoglucuronic acid is described. Small but significant amounts of the conjugate were also obtained from the 150,00 pellet and cytosol fractions. The addition of NADPH to the incubation media increased the yield of radioactive-estradiol-17 beta, 17-glucosiduronate perhaps by preserving the integrity of the C-17-hydroxyl group. As expected, the effect of the reduced nucleotide was more pronounced in the fractions other than the microsome. The biosynthesized conjugate was isolated and purified by multiple column chromatography and the structure was confirmed by derivative formation, enzyme hydrolysis and crystallization of the aglycone.

Estrogen metabolism in nonhuman primates. I. In vitro biosynthesis of estrogen glucosiduronates in rhesus monkey liver.

Estrone glucosiduronate, 17beta-estradiol-3-glucosiduronate, 17beta-estradiol-17-glucosiduronate and estriol-16alpha-glucosiduronate have been biosynthesized in substantial yield by incubation of radioactive estrone, 17beta-estradiol, estriol and uridine diphosphoglucosiduronic acid with rhesus monkey liver homogenates. The metabolites were characterized by chromatography on Celite and DEAE-Sephadex, enzyme hydrolysis, derivative formation and crystallization to constant specific activity. The percent conversion to 17beta-estradiol-17-glucosiduronate from 17beta-estradiol ranged between 56-71%; from estrone, the conversion was 49-54%. Other metabolites formed from estradiol were estrone glucosiduronate (12-21%) and 17beta-estradiol-3-glucosiduronate(5-12%). The same metabolites derived from estrone accounted for 18-28% and 10-14% respectively. After estriol incubation, more than 90% of the steroid was converted to estriol-16alpha-glucosiduronate with no detectable estriol-3-glucosiduronate. This report represents the first time that 17beta-estradiol-17-glucosiduronate has been reported as a metabolite in the rhesus monkey and this is the only known species which forms 17beta-estradiol-17-glucosiduronate as the predominant metabolite of either estrone or estradiol in vitro. Rhesus monkey liver is similar to the human and baboon in that it metabolizes estriol exclusively to estriol-16-glucosiduronate.

Identification of conjugated estrogen metabolites in dog plasma following administration of estriol-2,4,6,7-3H.

Following the constant infusion of 2,4,6,7-3H-estriol in male dogs for a period of 90 minutes, the radioactive metabolites present in arterial plasma were separated by solvent partition, DEAE-Sephadex, Celite partition and thin layer chromatography. The identities of the individual estrogens and estrogen conjugates were confirmed by specific activity determinations after chromatography in several different solvent systems, enzyme hydrolysis and chromatography of the unconjugated steroids and their derivatives.

PIP: Conjugated estrogen metabolites in arterial plasma were identified in male dogs by solvent partition, DEAE-Sephadex, Celite partition, and thin layer chromatography following constant infusion of tritiated-2,4,6,7-estriol for 90 minutes. Identification was confirmed by specific activity assessment in various solvent systems, enzyme hydrolysis and chromatography of the unconjugated steroids and their derivatives. All unconjugated and radioactivity after infusion was identified as free estriol, and 5 conjugated metabolites were isolated. 3 of these were identified as estriol-3-glucosiduronate, estriol-16alpha-glucosiduronate, and estriol-3-sulfate. 2 polyconjugates of estriol appeared to be estriol-3-sulfate-16alpha glucosiduronate and an estriol diglucosiduronate.

Prolactin and blood pressure responses to perphenazine in human subjects: comparison of the oral and intramuscular routes.

Although several phenothiazines are known to stimulate prolactin (PRL) secretion, only chlorpromazine is in general use for this purpose in humans. However, chlorpromazine has severe sedative and hypotensive effects. Therefore, the effects of perphenazine on human PRL release and on blood pressure were evaluated. Perphenazine was administered orally (8mg) and intramuscularly (5mg and 2mg) to determine the optimal route and dose for evaluating PRL release. The postural hypotensive effect of perphenazine was evaluated with the 2mg intramuscular (IM) dose. The mean time of peak PRL response (hr +/- SD) was significantly shorter (p less than 0.05) for the 5mg IM (1.7 +/- 0.4) than the oral (4.5 +/- 0.6) route. Also, the mean ratio of peak/baseline PRL was significantly greater for the 5mg IM (8.87 +/- 5.69) than the oral (5.12 +/- 2.90) route. The major side-effect produced by perphenazine was drowsiness, which was moderate to severe with the 5mg IM dose. A lower IM dose (2 mg) retained PRL releasing activity, reduced drowsiness, and did not produce hypotension. For clinical testing, intramuscular perphenazine is preferred over oral perphenazine because of the shorter latency period and the higher PRL levels. Intramuscular perphenazine (2 mg) is preferred to chlorpromazine since it did not produce a clinically significant hypotensive effect. This is the first report on the dynamic responses of PRL and blood pressure to intramuscular perphenazine in humans.

Brief Report: Differential oxidations of estradiol-17ß by the chimpanzee in vivo.

The metabolism of estradiol-17ß is primarily an oxidative process at either carbon-2 or carbon-16 in the human. The objective of this study was to determine the relative importance of these two oxygenation pathways in the chimpanzee. The rate of oxidation of estradiol-17ß at each position was determined by measuring the release of tritium into body water from carbon-2 or carbon-16. [2-3H]-Estradiol-17ß or [16-3H]-estradiol-17ß was injected intravenously into three adult male chimpanzees, and blood samples were obtained at several time intervals between 1 and 48 hr. The blood was lyophilized, and the release of tritium from the specifically labeled estrogens into the body fluid pool was determined. The release of tritium from the 16α-position was very low and did not exceed 3% in any animal. The release of tritium from the carbon-2 was much faster, amounting to 29%, 34%, and 35%, respectively, by 24 hr. The ratio of tritium released from carbon-2:carbon-16 was 5.0, 13.2 and 16.9, respectively, at 24 hr after injection of the specifically labeled estradiol-17ß. These results demonstrate clearly that the major pathway for oxidative metabolism of estradiol-17ß in the chimpanzee is via oxygenation at carbon-2, with the formation of catechol estrogens, as in the human.