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Naloxone (10 mg) was given intravenously to seven postmenopausal women not receiving hormone treatment and to six postmenopausal women receiving Premarin-Provera treatment during the Premarin phase and also during the Premarin-Provera phase of therapy. Baseline estrone and estradiol levels (mean +/- SEM) were significantly lower in the group not receiving hormones (46.0 +/- 5.2 pg/ml and 28.4 +/- 3.1 pg/ml, respectively) than in the group in the Premarin phase of therapy (154 +/- 14 pg/ml and 79 +/- 13 pg/ml) and the group in the Premarin-Provera phase (135.1 +/- 8.3 pg/ml and 57.5 +/- 3.0 pg/ml) (p less than 0.005). Follicle-stimulating hormone, luteinizing hormone, and prolactin levels were 118.7 +/- 5.3 mIU/ml, 118.7 +/- 9.5 mIU/ml, and 9.2 +/- 0.7 ng/ml, respectively, with no significant change after naloxone administration in untreated women. With hormone therapy the basal follicle-stimulating hormone and luteinizing hormone levels decreased significantly while basal plasma estrone and estradiol increased significantly. In both the group in the Premarin phase of therapy and the group in the Premarin-Provera phase, luteinizing hormone levels increased significantly at 30 (135% +/- 10%, 144% +/- 8%), 45 (150% +/- 12%, 133% +/- 11%), 60 (149% +/- 15%, 128% +/- 11%), and 90 (139% +/- 15%, 132% +/- 13%) minutes after naloxone administration (p less than 0.01 to p less than 0.001). Follicle-stimulating hormone levels did not change significantly whereas prolactin levels showed a trend toward a decrease. These findings indicate that opioid inhibition of gonadotropins is reduced in postmenopausal women but increased with Premarin-Provera treatment. The effect of sex steroid on the opioid system in the postmenopausal women differs from that in the premenopausal women.

We have measured the concentrations of circulating oxytocin and the 13, 14-dihydro, 15-keto-metabolite of prostaglandin F2 alpha (PGFM) in women during preterm labor. Twelve women were given intravenous ethanol and 11 women received intravenous ritodrine for the prevention of preterm birth. Blood samples were obtained before and 1/2, 1, 2, 4, 12, and/or 24 hours after treatment began. On admission, the plasma concentrations of both oxytocin and PGFM were raised over levels observed in women with normal pregnancies of similar gestational age, 25 to 36 weeks. The initial oxytocin level was 58.5 +/- 8.2 pg/ml (mean +/- SE, n = 23) and the mean initial PGFM level was 264 +/ 33.1 pg/ml (n = 15); both values were significantly higher than in 10 control subjects (17.4 +/- 4.8 and 156 +/- 21.8 pg/ml, respectively). During infusion of ethanol, the plasma oxytocin level fell rapidly, the levels at 1/2 and 1 hour after infusion being significantly lower than before the infusion (29.0 +/- 5.5 and 27.8 +/- 3.5 pg/ml, respectively). The plasma oxytocin level remained low in women in whom the treatment arrested labor and prevented preterm birth (n = 8) but rose 2 to 4 hours after the infusion began in women in whom the treatment failed to arrest labor (n = 4). Ritodrine, on the other hand, had no significant effect on circulating oxytocin levels. The plasma PGFM level decreased significantly during ritodrine treatment only in the successfully treated patients. Ethanol had no consistent effect on plasma PGFM levels in the four patients in whom PGFM levels were measured. In the ritodrine-treated patients, the plasma PGFM level was positively correlated with the frequency of uterine contractions whereas in the ethanol-treated patients a correlation of plasma oxytocin to the frequency of contractions was observed. Thus, oxytocin secretion is increased during preterm labor, and the release of prostaglandin F is also increased. While it is not possible to determine whether any or both of these oxytocic agents actually trigger preterm labor, both seem to play a role in its mechanism.

Seventeen human fetal and neonatal pituitary glands were removed at necropsy, and analyzed for oxytocin content by a specific and sensitive radioimmunoassay, after homogenization in 0.4M acetic acid. Serial dilution of the pituitary extract showed parallelism with the oxytocin standard curve on the radioimmunoassay. Column chromatography of the pituitary gland extract gave a single peak of immunoreactive oxytocin as determined by the radioimmunoassay. In eight fetuses, 14 to 17 weeks' gestation, pituitary gland oxytocin was 10.2 +/- 5.9 ng/gland (mean +/- SE), whereas an 18-week fetus had 5.8 ng of oxytocin per gland. Pituitary gland oxytocin content increased to 38.4 ng/gland in a 20-week fetus removed at hysterectomy, and 31.6 ng/gland in a 26-week fetus. Fetal pituitary gland oxytocin values were 22.1 ng/gland and 57.0 ng/gland at 32 weeks and increased significantly to 544.3 +/- 33.8 ng/gland in 1- to 5-day-old term newborn infants (n = 3). However, a 13-day-old term newborn infant had 3.7 ng of oxytocin per pituitary gland. The increased pituitary gland oxytocin content with advancing gestation was due to a significant increase in oxytocin concentration rather than to an increase in the weight of the pituitary gland. The findings indicate that oxytocin is present in fetal pituitary glands as early as 14 to 17 weeks' gestation and increases at term to 50 and 13 to 14 times more than in early midtrimester and early third-trimester pregnancy, respectively.

Plasma concentrations of oxytocin (OT) were determined by a highly specific and sensitive radioimmunoassay in (1) nine pregnant women near or at term who were given 400 units of buccal OT every 20 minutes to induce labor or to augment uterine contractions; (2) four adult males who were given 200 units and 400 units of buccal OT every 20 minutes in two separate experiments each lasting 2 hours; and (3) three adult males at regular intervals up to 45 minutes after discontinuation of buccal OT. Plasma concentrations of OT increased in all the women studied, and exceeded 50 picograms per milliliter in six of nine patients after buccal OT was given. However, the net increase in OT was less than 50 pg/ml in six of nine patients. In males, 90% of the plasma samples collected when 400 units of OT was given had detectable levels of OT, with mean levels of 24 to 32 pg/ml; when 200 units was used, only 53% of the plasma samples had detectable OT, and mean levels were consistently below 10 pg/ml. Plasma OT decreased to one third but not to baseline levels in the course of 45 minutes after OT was discontinued. The findings indicate that with 400 units of buccal OT every 20 minutes, plasma OT concentrations attained were similar to those found during the first stage of labor, and that the disappearance of OT from the plasma after discontinuation was slow.

To determine the effect of oral contraceptives on endogenous opioid modulation of the hypothalamic-pituitary axis, we gave a bolus dose of 10 mg of naloxone intravenously in women using Lo/Ovral-28 oral contraceptives and in normal (control) women during the follicular (days 8 to 9) and luteal (days 21 to 23) phases. Plasma follicle-stimulating hormone, luteinizing hormone, and prolactin were measured by radioimmunoassay before and after naloxone at regular intervals. In oral contraceptive users (n = 5) basal plasma follicle-stimulating hormone (3.7 +/- 0.4 mIU/ml) and luteinizing hormone (3.2 +/- 0.5 mIU/ml) levels were significantly lower than in control subjects during both follicular (10.7 +/- 0.9 and 16.7 +/- 2.0) and luteal (7.7 +/- 1.4 and 10.0 +/- 0.9, respectively) phases (p less than 0.05 to 0.001). In contrast the basal plasma prolactin level was significantly higher in oral contraceptive users (25.0 +/- 4.1 ng/ml) than in control subjects during the follicular (11.8 +/- 1.2) and luteal (11.0 +/- 0.8) phases (p less than 0.01). In control subjects, follicle-stimulating hormone, luteinizing hormone, and prolactin levels did not change significantly after naloxone in the follicular phase, but naloxone elicited a significant synchronous release of luteinizing hormone and prolactin during the luteal phase. In contrast, oral contraceptive users showed increases in luteinizing hormone and prolactin after naloxone that were not significantly different from the basal plasma levels.

Oxytocin concentrations were determined in baboon (Papio anubis) corpora lutea, and the effect of oxytocin on dispersed luteal cell progesterone production was evaluated. Oxytocin concentrations increased significantly from an early luteal phase value of 2.1 +/- 1.1 ng/gm to a peak concentration of 18.1 +/- 4.3 ng/gm wet weight in midluteal phase corpora lutea. Corpora albicantia and ovarian stroma had comparatively low oxytocin concentrations. Reverse-phase high-pressure liquid chromatography of corpora lutea extracts gave a peptide peak (retention time, 17.25 min) similar to a standard oxytocin peak. Plasma oxytocin levels, which were significantly higher in the ovarian vein draining a corpus luteum than in the contralateral side or the femoral vein, declined significantly after luteectomy. Oxytocin was localized by immunocytochemical methods in luteal cells. In the early luteal phase oxytocin (4 to 800 mU; 1 mU is equivalent to 2 ng) inhibited basal and human chorionic gonadotropin-stimulated progesterone production by dispersed luteal cells, but in the late luteal phase 200 to 800 mU oxytocin inhibited only human chorionic gonadotropin-stimulated progesterone output. Oxytocin did not affect luteal cell progesterone production in the midluteal phase. Thus oxytocin is present in corpora lutea, can be localized in the luteal cells, is probably produced locally, and may modulate luteal cell progesterone production.

Determined by a sandwich, solid-phase radioimmunoassay with mouse monoclonal antibody, OC 125, plasma CA 125 levels were significantly elevated in stage III (mean +/- SEM = 32.7 +/- 5.2 U/ml, n = 17, p = less than 0.01) and stage IV endometriosis (37.2 +/- 10.5 U/ml, n = 6, p = less than 0.005) compared with levels during the follicular (15.9 +/- 1.5 U/ml, n = 12) and secretory phases (15.8 +/- 1.3 U/ml, n = 15) of control women and users of oral contraceptives (15.5 +/- 1.2 U/ml n = 10). However, CA 125 levels were not significantly elevated in women with stage I (16.6 +/- 2.0 U/ml, n = 28) or stage II endometriosis (17.9 +/- 2.1 U/ml, n = 13). Peritoneal fluid levels of CA 125 (n = 14) were significantly higher (2 to 9.3 times) than the corresponding paired plasma levels in participants with stage I, II, or III endometriosis. In patients treated with danazol (n = 10) or buserelin (n = 17), plasma CA 125 levels decreased significantly by midtherapy, remained suppressed at the end of therapy, but rebounded to near pretreatment levels 6 months after treatment was completed. With gestrinone therapy a similar decline was observed but became significant only at the end of therapy. Our findings indicate that elevated plasma CA 125 levels may prove useful in the management of endometriosis.

To determine the site of oxytocin in human ovaries and its relationship with ovarian steroids, oxytocin and steroid hormones were measured in ovarian tissues, ovarian vein, and peripheral blood. Corpus luteum had significantly higher oxytocin, estrone, estradiol, and progesterone concentrations than corpus albicans and ovarian stroma (p = less than 0.01 to less than 0.001). Oxytocin concentrations in corpus luteum correlated significantly with estrone, estradiol, and progesterone. Oxytocin in corpus luteum increased from 14.0 +/- 1.8 ng/gm of wet weight in early to 30.8 +/- 0.9 ng/gm in midluteal phases (p = less than 0.001). Reverse phase high pressure liquid chromatography showed similarity between oxytocin in corpus luteum and synthetic oxytocin. Ovarian vein draining corpus luteum had significantly higher plasma oxytocin (11.8 +/- 1.5 pg/ml) than those without corpus luteum (2.1 +/- 0.2 pg/ml) or in the peripheral blood (2.9 +/- 0.3 pg/ml) (p = less than 0.001). Oxytocin in corpus luteum correlated significantly with its ipsilateral ovarian vein level of oxytocin, estrone, progesterone, and 17 alpha-hydroxyprogesterone. Our findings demonstrate that oxytocin is present and probably produced in corpus luteum and secreted into its ovarian vein; it may regulate corpus luteum release of progesterone, 17 alpha-hydroxyprogesterone, and estrone.

Twelve pregnancies, in which the initial serum hCG titer as measured by RRA was subnormal, were studied to determine if a hormonal profile would serve as a prognostic index of spontaneous abortion. Three of the 12 patients delivered term babies. The hCG titers remained subnormal throughout the pregnancy, however, the serum E2, P, 17alpha-OHP, and PRL remained normal. One of the 12 patients aborted in week 25 of gestation. The serum hCG and PRL were subnormal; however, the serum E2, P, and 17alpha-OHP were normal. Eight of the 12 patients aborted prior to 100 days' gestation. The serum hCG, E2, and PRL were subnormal whereas the P and 17alpha-OHP were normal. Therefore, in patients who have subnormal serum hCG titers, serum E2 and PRL may provide a prognostic index of spontaneous abortion.

Maternal and umbillical arterial and venous plasma and amniotic fluid testosterone (T) and dihydrotestosterone (DHT) were measured by radioimmunoassay. Maternal plasma T was 690 +/- 80 pg. per milliliter (mean +/- S.E.) in early pregnancy (less than 20 weeks) and increased significantly (p = 0.0002) to 1,095 +/- 177 pg. per milliliter in late pregnancy (greater than 20 weeks). DHT was 113.0 +/- 18.8 pg. per milliliter in early pregnancy and 179.8 +/- 30.5 pg. per milliliter in late pregnancy. Both umbilical arterial (UA) and umbilical venous (UV) plasma T were significantly higher in 11 male infants (UA T = 135.6 +/- 16.5 pg. per milliliter; UV T = 227.5 +/- 40.8 pg. per milliliter) than in 12 female infants (UA T = 92.1 +/- 9.7 pg. per milliliter; UV T = 89.6 +/- 12.6 pg. per milliliter) (p = less than 0.05 and less than 0.005, respectively). UV DHT and UA DHT showed no significant difference between male and female neonates. In midtrimester pregnancy, amniotic fluid T (AFT) was 165.2 +/- 15.4 pg. per millitier in pregnancies with a male fetus and was significantly higher (p = less than 0.001) than in pregnancies with a female fetus (mean +/- S.E. = 27.6 +/- 2.6 pg. per millitier). In late pregnancy, AFT levels were similar to those of early pregnancy, but a considerable overlap in AFT between fetuses of both sexes was observed. DHT was not detectable in amniotic fluid. The results suggest the potential value of AFT for determining fetal sex in midtrimester pregnancy and confirm that maternal T and DHT increase during pregnancy and that cord T levels reflect fetal gonadal androgen synthesis.

Fetal adrenal steroids have been shown to be important in the timing of parturition. Since dehydroepiandrosterone sulfate is converted to estrogen, which is important in cervical softening, levels of dehydroepiandrosterone sulfate together with those of estradiol, estriol, and progesterone were measured and compared in pregnant women undergoing induction of labor with ripe and unripe uterine cervices. While there were no differences between the levels of estradiol, estriol and progesterone in the two groups of women, dehydroepiandrosterone sulfate was significantly elevated in the group of women with ripe cervices. These findings suggest that cervical changes preceding the onset of labor are associated with a significant elevation of maternal dehydroepiandrosterone sulfate levels. Changes in maternal plasma estradiol, estriol, and progesterone levels do not appear to be clinically related to cervical ripeness.

Daily plasma testosterone (T) and dihydrotestosterone (DHT) as well as plasma lueteinizing hormone, plasma estradiol (E2) and plasma progestrone (P) were measured by radioimmunoassay in seven ovulatory cycles and in three anovulatory cycles. In ovulatory cycles, plasma T ranged from 110 to 637 pg. per milliliter, while plasma DNT ranged from 10 to 246 pg. per milliliter. There is an increase in the mean plasma T during the early follicular phase of the cycle with a fall on the day of ovulation. Plasma T levels rise again during the early luteal phase and drop during the late luteal phase of the cycle. Plasma E2 rises during the follicular phase with a preovulatory surge followed by a drop after ovulation and a subsequent secondary rise. Plasma P was less than 1 ng. per milliliter during the follicular phase and increased to above 5 ng. per milliliter after ovulation, reaching levels of 20 to 25 ng. per milliliter during the luteal phase. In anovulatory cycles, there is random fluctuation with no well-defined patterns. Plasma P remained below 1 ng. per milliliter throughout the cycle. The finding of maximum T levels prior to midcycle may reflect increased T production by the ovaries in response to increasing levels of follicle-stimulating hormone. There is little fluctuation in the levels of T during the menstrual cycle. These findings obviate the need for multiple plasma T estimations in the assessment of women with hirsutism, polycystic ovarian disease, and the testicular feminization syndrome.

To assess fetal oxytocin release in relation to maternal oxytocin, serial paired maternal (femoral artery) and fetal (aorta) plasma oxytocin were determined by a specific and sensitive radioimmunoassay during pregnancy and parturition in the sheep. The maternal oxytocin level was 29.1 +/- 2.6 pg/ml (mean +/- SE) but was significantly lower than fetal oxytocin levels of 45.8 +/- 4.3 pg/ml (p less than 0.001). There was a significant correlation between paired maternal oxytocin and fetal oxytocin levels throughout late pregnancy (r = 0.2523, p less than 0.05). Maternal oxytocin levels calculated for every 5 days' gestation ranged from 15.8 +/- 2.7 to 32.7 +/- 5.6 pg/ml while the corresponding fetal oxytocin levels (21.6 +/- 3.5 to 62.5 +/- 21.6 pg/ml) were always higher (92 to 135 days) but not significantly different. However, at 136 to 142 days' gestation, fetal oxytocin levels (63.9 +/- 14.1 pg/ml) were significantly higher than maternal oxytocin levels (20.1 +/- 3.3 pg/ml) (p less than 0.01). Based on observations in two animals, fetal oxytocin levels appeared higher than maternal oxytocin levels at parturition with an increase a few days before labor. Our findings indicate that, in the sheep, fetal oxytocin levels were usually higher than but not significantly different from maternal oxytocin levels and that fetal oxytocin levels changed in relation to labor, suggestive of fetal release of oxytocin.

Paired samples of blood and saliva from 37 men and nine women throughout the menstrual cycle were measured for testosterone by radioimmunoassay and free testosterone by equilibrium dialysis. There was a highly significant correlation between plasma and salivary testosterone, with a correlation coefficient r = 0.71 (p = less than 0.001). In men, free testosterone constituted 78% of salivary testosterone but only 4% of plasma testosterone; mean +/- SE salivary testosterone was 193.7 +/- 6.7 pg/ml compared to plasma testosterone of 5,140 +/- 298.0 pg/ml. Salivary testosterone decreased significantly from a morning (0800 hours) level of 208 +/- 7.5 to an evening (1800 hours) level of 174 +/- 8.4 pg/ml (p = less than 0.001) (n = 23). Similarly, plasma testosterone was significantly higher in the morning (6,584 +/- 472 pg/ml) than in the evening (5,571 +/- 357 pg/ml) (p = less than 0.005) (n = 25). Free testosterone in saliva and plasma also showed significantly higher morning than evening levels. The coefficients of variability for hourly changes (0900 to 1800 hours) in salivary testosterone and free testosterone were 13.6% and 16.7% compared to 12.7% and 20.9% for plasma testosterone and free testosterone, respectively. In women, salivary testosterone during the proliferative phase of the menstrual cycle was 108.3 +/- 5.8 pg/ml, and it increased significantly to 130.5 +/- 6.0 pg/ml in the secretory phase (p = less than 0.02). Our findings indicate that measurements of salivary testosterone reflect plasma testosterone and may be a useful noninvasive method of assessing levels of testosterone.

Serum progesterone was assayed by the competitive protein-binding technique in 20 cases of gestational choriocarcinoma and one case of nongestational choriocarcinoma. Serum human chorionic gonadotropin (HCG) was simultaneously measured from the same blood samples by the hemagglutination-inhibition technique. Serum progesterone in choriocarcinoma ranged from 1.3 to 182.9 ng. per milliliter with a mean +/- standard error of the mean of 36.2 +/- 10.2 ng. per milliliter. Serum HCG ranged from 0.6 to 1,280 I. U. per milliliter. In 11 patients with choriocarcinoma, serum progesterone levels were indistinguishable from values obtained during the luteal phase of the normal menstrual cycle; six patients had values similar to those found in early normal pregnancy and four patients with postmolar villous choriocarcinoma had elevated serum progesterone. There was a significant correlation between serum HCG and serum progesterone (r = + 0.5652, p = 0.005). The significance of these findings is discussed with reference to the likely source of progesterone in choriocarcinoma.

Peritoneal fluid obtained at laparoscopy from 49 women was measured for its content of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), 6-keto-prostaglandin F1 alpha (6-KF), and thromboxane B2 (TxB2) by specific radioimmunoassays. In normal women (n = 10), the concentrations of prostaglandins in peritoneal fluid were (mean +/- SE): PGE2 = 0.79 +/- 0.26, PGF2 alpha = 0.60 +/- 0.18, 6-KF = 0.48 +/- 0.19, and TxB2 = 0.23 +/- 0.09 ng/ml; in women with endometriosis (n = 16): PGE2 = 1.43 +/- 0.72, PGF2 alpha = 1.52 +/- 0.59, 6-KF = 3.32 +/- 0.71, and TxB2 = 1.14 +/- 0.69 ng/ml; in women with chronic pelvic inflammatory disease and/or obstructed tubes (n = 19): PGE2 = 1.94 +/- 1.04, PGF2 alpha = 1.20 +/- 0.61, 6-KF = 1.55 +/- 0.40, and TxB2 = 0.64 +/- 0.24 ng/ml; in women with pelvic pain without any visible pathologic condition (n = 4): PGE2 = 1.11 +/- 0.66, PGF2 alpha = 0.73 +/- 0.55, 6-KF = 1.35 +/- 0.35, and TxB2 = 0.39 +/- 0.17. The mean volumes of peritoneal fluid recovered were 10 to 16 ml and were not significantly different between the groups. Except for a significantly elevated concentration of 6-KF in the peritoneal fluid of women with endometriosis compared to normal women (p = less than 0.02), the prostaglandins measured did not differ significantly between the groups of women studied. The possible significance of elevated 6-KF in the peritoneal fluid of women with endometriosis is discussed.

To determine if the prostaglandin synthetase inhibitors ibuprofen and flurbiprofen can suppress postoperative adhesion formation, New Zealand White rabbits that had uterine tubal ligation underwent uterine tube reanastomosis and were given either saline solution (controls), 75 mg of ibuprofen intravenously every 6 hours, or 12.5 mg of flurbiprofen intravenously every 6 hours for 8 doses after operation. Both ibuprofen and flurbiprofen significantly reduced postoperative adhesions (p less than 0.025). With histologic indices of tissue reunion, ibuprofen and flurbiprofen were associated with significantly less scar thickness than controls (p less than 0.001) but did not have any significant effect on mucosal regeneration, foreign body reaction, and muscularis disruption. When all four histologic indices were compared, flurbiprofen but not ibuprofen had a significantly lower score than controls, indicating the greater potency of flurbiprofen over ibuprofen. Our findings show that ibuprofen and flurbiprofen can suppress perioperative and postoperative surgically induced inflammatory response associated with healing and thereby reduce adhesion formation and scar thickness.

Unconjugated and conjugated estradiol-17beta (E2) were measured in the sera of four patients with hydatidiform mole at frequent intervals after removal of the mole, in the left and right ovarian vein blood in a patient with hydatidiform mole, in the peripheral sera and serous fluid of the molar vesicles in seven cases of hydatidiform mole, and in the fluid from the left and right theca lutein cyst (TLC) of a molar pregnancy, by a radioimmunoassay method. Patients with highly elevated serum E2 had a rapid clearance of E2 within 24 to 36 hours after removal of the mole; those with minimal E2 elevation had a slower clearance of the hormone from the circulation. Mole vesicle fluid had undetectable E2 but a wide range of unconjugated E2 which was usually lower than in the peripheral blood. Both ovarian vein blood and TLC fluid have higher E2 concentrations than the peripheral blood. The significance of these findings is discussed in relation to the contribution of the trophoblast and the ovaries to the circulating E2.

With increasing use of amniocentesis for high-risk pregnancies, measurement of amniotic fluid hormone levels could prove to be a pratical value. Protein steroid hormones as well as prostaglandins in amniotic fluid are reviewed. The source and entry of each hormone, their concentrations, and their possible physiologic role in pregnancy are discussed. Changes in the level of hormones in amniotic fluid or pregnancies with complications jeopardizing fetal well-being are referred to, and their significance is discussed. Since amniotic fluid is close to the myometrium, changes in some amniotic fluid hormones might be responsible for or associated with the onset of labor.

Serum progesterone was measured by competitive protein-binding assay in 331 cases of normal pregnancy ranging from 6 to 42 weeks. Serial estimations of serum progesterone were performed in nine cases of severe hypertensive disorder of pregnancy, eight cases of twin pregnancy, three cases of twin pregnancy complicated by severe hypertensive disorder of pregnancy, three cases of triplet pregnancy, three cases of previous bad obstetric history, one case of anencephaly, and seven cases of intrauterine fetal death. Serum progesterone remained within normal range in severe hypertensive disorder of pregnancy and the levels were indistinguishable in cases of fetal growth retardation from those without growth retardation. In twin and triplet pregnancies, serum progesterone was within normal range or elevated and was usually higher than normal in twin pregnancies after weeks 33 to 34. Serum progesterone levels were normal in anencephalic pregnancy and in most cases of intrauterine fetal death. The findings are discussed with reference to placental hormonal activity. It is concluded that serum progesterone is a poor index of placental function.

Serial assays of serum progesterone and serum human chorionic gonadotropin (HCG) were performed in eight cases of choriocarcinoma before and during treatment of the disease. Serum progesterone was measured by the competitive protein-binding technique and serum HCG was measured by the hemagglutination inhibition method. Serum HCG gives a better index of response of the tumor to treatment when compared to serum progesterone. In cases where the ovaries are still present serum progesterone does not disappear completely when the disease is eradicated and fluctuates cyclically, thus reflecting ovarian activity. However, in most cases with pulmonary secondaries, serum progesterone was elevated in spite of undetectable serum HCG. With widespread metastases serum progesterone rose to pregnancy levels and remained persistently high. Cerebrospinal fluid progesterone in a case of choriocarcinoma with cerebral metastasis was 5 ng. per milliliter, which was very much higher than in normal pregnant subjects. The findings of serum progesterone in comparison to serum HCG during therapy of choriocarcinoma are discussed.

To determine the temporal relationship between immunoreactive chorionic gonadotropin, chorionic gonadotropin receptors, and implantation of the rabbit blastocyst, (1) immunoreactive chorionic gonadotropin in plasma, uterine flushings and blastocysts; (2) chorionic gonadotropin receptors on blastocysts (day 5 and 6) and embryonic and interembryonic segments of the uterus (day 7); and (3) chorionic gonadotropin receptors on the endometrium and myometrium (day 1 through 6) were measured. Binding of I125-labeled beta-subunit of human chorionic gonadotropin (hCG) by cell membranes from blastocysts increased significantly from 6.0 +/- 1.1 fmol/mg of protein (mean +/- SE) on day 5 (N = 6) to 16.1 +/- 1.3 fmol/mg of protein on day 6 (n = 6) (P less than 0.001). Immunoreactive chorionic gonadotropin levels in blastocyst fluid increased from 0.3 ng/ml of day 5 to 0.65 ng/ml on day 6. Specific binding of I125-labeled hCG was absent in endometrial and myometrial cell membranes before implantation (days 1 to 6) but was found in decidual cells from embryonic segments on day 7. Plasma immunoreactive chorionic gonadotropin or chorionic gonadotropin--like material increased from 6 ng/ml of day 1 to 52 ng/ml on day 7. Uterine flushings had chorionic gonadotropin levels of 0.4 ng/ml of day 2, which increased slowly to 1.0 ng/ml on day 7. Intrauterine instillation of hCG into nonpregnant uterine horns demonstrated transuterine absorption of hCG with plasma hCG levels showing a dose-related response. Our findings demonstrate that (1) immunoreactive chorionic gonadotropin or chorionic gonadotropin--like material is detectable in plasma, uterine flushings, and blastocyst fluid before implantation, (2) chorionic gonadotropin receptors are present on the blastocyst cells before implantation, and (3) the uterus can absorb chorionic gonadotropin from its lumen.