Maternal Plasma Estradiol Research Articles

Testosterone and estradiol in maternal plasma and their relation to fetal sex

Testosterone and estradiol in maternal plasma and their relation to fetal sex

Dietary fat intake and gestational weight gain in relation to estradiol and progesterone plasma levels during pregnancy: a longitudinal study in Swedish women

BackgroundElevated pregnancy hormone levels, such as oestrogen and progesterone, may increase the risk of developing breast cancer both in mothers and offspring. However, the reasons for large inter-individual variations in estrogen and progesterone levels during pregnancy remain unknown. The objectives of this study were to investigate whether a) intakes of total dietary fat, types of fat (monounsaturated: MUFA, polyunsaturated: n-3 and n-6 PUFA, and saturated) and b) gestational weight gain are associated with estradiol and progesterone levels in plasma during pregnancy.MethodsWe measured body weight as well as estradiol and progesterone in plasma among 226 healthy pregnant Swedish women on gestation weeks 12, 25 and 33. At the same time points, dietary intake of total fat and types of fat (MUFA, PUFA, SFA, n-3 and n-6 PUFA) were estimated using 3-day food diaries.ResultsA large variation in estradiol and progesterone levels was evident.Nulliparous women had 37%, 12% and 30% higher mean estradiol levels on gestation weeks 12, 25 and 33 compared to parous women (P = 0.008). No associations were found between dietary intake of total fat or fat subtypes (including n-3 PUFA and n-6 PUFA) and plasma estradiol or progesterone levels. Gestational weight gain was associated with progesterone levels (P = 0.03) but the effect was very small (20% increase in progesterone levels between gestational weeks 12 and 33 per kg body weight/week).ConclusionNo associations among gestational weight gain, maternal dietary fat intake (total or subtypes including n-3 PUFA and n-6 PUFA) and plasma estradiol levels were found. However, pregnancy progesterone levels correlated with weight gain during pregnancy. Identification of other possible determinants of pregnancy estradiol and progesterone levels, important for the development of breast cancer in both mothers and offspring, are needed.

Some biological effects of scorpion envenomation in late pregnant rats

Scorpion envenoming is less studied during gestation; however, it may induce various biological disturbances in maternal organism and hypothetical ones on their fetuses. The scope of this report was to elucidate some biological effects of such poisoning in late pregnant rats. Hence, TBARS levels in maternal lung, placental and fetal pulmonary and hepatic tissues and dam's biochemical blood parameters (glucose, creatinine, 17-β estradiol, progesterone, blood nitrogen urea, sodium and potassium maternal plasma concentrations) had been evaluated after saline (G1), and scorpion venom (G2: 30 min and G3: 60 min) injections in 22nd day pregnant rats. Histological microscopic examination of these tissues was also carried out in HE-stained paraffin sections. In addition, the mean arterial blood pressure following the envenomation variations was measured in three rats from the same pool. Our results showed that Buthus occitanus tunetanus crude venom induced significant increase in maternal, placental and fetal tissues lipid peroxidation, concomitant with blood pressure elevation. Maternal plasma creatinine, estradiol and progesterone concentrations levelled up significantly after 30 min or later (60 min) after the venom injection. Except for a probable pronounced oedema and few congestions in maternal lungs and degenerative aspects of trophoblast cells, all examined tissues showed a conserved structure. These results suggest that scorpion envenomation may induce gestation process disturbances and threatens both mother's and fetus’ well-being.

Regulation of Membrane-Associated Prostaglandin E2 Synthase 1 in Pregnant Sheep Intrauterine Tissues by Glucocorticoid and Estradiol

This study was designed to determine the regulatory effect of glucocorticoid and estradiol on expression of ovine intrauterine membrane-associated prostaglandin E(2) synthase 1 (mPTGES1) in late gestation and at labor. For gestational and labor groups, 16 pregnant ewes from 95-147 d gestational age (dGA) and four pregnant ewes at spontaneous term labor were used. The fetal glucocorticoid group, 14 pregnant ewes at 123-125 dGA with fetuses, was divided into the following groups: after sham adrenalectomy (n = 5), adrenalectomy (n = 4), and adrenalectomy with fetal cortisol replacement to late gestation levels (n = 5). For the maternal glucocorticoid group, nine pregnant ewes were treated with saline (n = 4) and three courses of maternal dexamethasone (n = 5). For the estradiol group, 10 pregnant ewes at 119-121 dGA were treated with sesame oil (n = 5) or estradiol (n = 5) to produce labor levels of estradiol in maternal plasma. Endometrial, myometrial, and placental mRNA and proteins were analyzed by Northern and Western blot and immunocytochemistry for mPTGES1. Data were analyzed by Student's t test and ANOVA. There was a significant increase of placental mPTGES1 in late gestation. Glucocorticoids, given to the mother or fetus, significantly stimulated mPTGES1 in placenta. mPTGES1 was elevated only in the endometrium during spontaneous term labor and after estradiol treatment. The mPTGES1 was localized in the myometrial smooth muscle cells, endometrial stromal cells, and placental trophoblast cells. Our study suggested that increased expression of placental mPTGES1 throughout late gestation might result from the increased fetal and maternal circulating glucocorticoids, whereas elevated maternal plasma estradiol concentration might be responsible for the induced mPTGES1 expression in the endometrium during labor.

Effects of 17-β-estradiol treatment of female zebra finches on offspring sex ratio and survival

Treatment of female zebra finches ( Taeniopygia guttata) with 17-β-estradiol leads to a female-biased sex ratio in their offspring at the age of independence [Horm. Behav. 35 (1999) 135]. It is unclear whether this is due to a bias of the primary sex ratio or to sex-specific survival. We replicated this experiment and found again a significantly higher total number of daughters than sons at independence in the estradiol-treated group. This was due to higher embryonic survival of daughters compared with sons in the estradiol-treated group and the reverse in the control group. There was no effect of the hormone treatment on the primary sex ratio. Treatment with 17-β-estradiol led to a significantly shorter hatching time and to heavier offspring at day 7 after hatching. This weight was correlated with maternal plasma estradiol levels on the day of the first egg, which were significantly higher in the estradiol-treated group than in the control group. The results do not support the idea that maternal estradiol levels influence the primary sex ratio. They indicate that maternal estradiol differentially affects survival of sons and daughters via an influence on the embryonic environment, possibly enhancing offspring growth.

40PREDICTORS OF CLONED CALF VIABILITY

The high rate of gestational loss in nuclear transfer (NT) pregnancies is a major economic and animal cost, preventing the widespread use of the technique. It is currently not possible to predict which early gestation fetuses will remain viable to term. As placental abnormalties are commonly associated with nonviable fetuses, placental proteins such as pregnancy specific protein (PSP 60, Heyman et al., 2002 Biol. Reprod. 63, 1787–1794; or PSPb Hill et al., 2000 Biol. Reprod. 66, 6–13) have been investigated as possible markers of viable pregnancy. To build upon these studies, we explored the predictive value of Day-35 maternal serum PSPb value to final cloned-calf viability; PSPb profiles throughout pregnancy; and the relationship of maternal plasma estradiol levels to calf viability. Maternal serum was sampled for PSPb at the time of the first ultrasound pregnancy examination (Day 35) to determine fetal number and viability (heartbeat). PSPb values were determined using an RIA by Dr. Garth Sasser (BioTracking, Moscow, ID). Median PSPb values were compared using the Kruskal-Wallis one-way ANOVA test on ranks. PSPb levels from failed single and twin pregnancies were significantly different from those of AI bred controls (P<0.05). PSPb levels from failed singles were not significantly different from those of viable single pregnancies although only nonviable cloned pregnancies had PSPb values >7.5. As PSPb levels at Day 35 were not highly predictive of viable outcome, we detailed the gestational PSPb profile for a different group of cows (n=40) that carried cloned pregnancies beyond Day 90. PSPb was determined at Days 35, 50, 65, and 90, then monthly to Day 240. Although there was no clear statistical significance, PSPb levels from nonviable cloned pregnancies were consistently higher at each time point than for viable pregnancies (14 cows gave birth to live calves) and significantly higher than those of controls. At term, plasma estradiol concentrations were assessed in a group of 5 NT pregnancies. Estradiol was investigated as cloned pregnancies often show a lack of readiness for parturition (e.g. lack of udder development, prolonged gestation, dysmature calves). These 5 pregnancies produced 3 highly viable NT calves: 1 with lowered viability that survived only with a high level of intensive care, and 2 nonviable despite a high level of assistance. In this small group, estradiol levels on the day of birth rose in parallel with viability (viable, 662pg; lowered viability, 170pg; nonviable, 76pg). This is a clinical observation rather than a statistical trend that suggests further investigation may be warranted. In summary, our results suggest maternal PSPb levels have value in identifying the outliers in a population of cloned pregnancies and that term-cloned pregnancies may show abnormally low maternal estradiol concentrations at term. Table 1

Prostaglandin mediates premature delivery in pregnant sheep induced by estradiol at 121 days of gestational age.

The experiments reported here were designed for both in vivo and in vitro approaches in the same animals to obtain a better picture of the role of estrogen in the control of parturition. Chronically catheterized pregnant ewes were treated with vehicle (n = 5) or estradiol (n = 6), 5 mg twice a day, im for 2 d starting at d 119 of gestation. Maternal and fetal plasma estradiol, progesterone, and cortisol were measured by RIA and maternal plasma prostaglandin (PG) F2alpha was measured by enzyme immunoassay. Intrauterine PG H synthase 2 mRNA and protein and placental P450(c17)alpha hydroxylase mRNA were determined by Northern, in situ hybridization, Western blot analysis, and immunocytochemistry. Data were analyzed by ANOVA. Five of six estradiol-treated ewes delivered their fetuses within 48 h; however, the placenta was still retained 5-6 h after fetal delivery. Both maternal plasma estradiol and PGF2 alpha increased significantly in the estradiol-treated group. Maternal and fetal plasma progesterone and cortisol were not altered in either group. There were significant increases of PGH synthase 2 mRNA and protein in myometrium, endometrium, and maternal placenta but not in fetal placenta in estradiol-treated ewes. Placental P450(c17)alpha hydroxylase mRNA was not detectable in vehicle or estradiol-treated groups. Estradiol can, in the absence of increase in plasma cortisol, stimulate uterine PG production and induce labor, resulting in fetal delivery in the sheep. Failure of placental delivery after estradiol treatment suggests that estradiol alone is insufficient to stimulate some of the key changes required to complete delivery at the stage of gestation studied.

Androstenedione treatment of pregnant baboons at 0.7-0.8 of gestation promotes a premature forward shift in the nocturnal maternal plasma estradiol surge relative to progesterone and increases myometrial contraction activity.

Androstenedione treatment of pregnant monkeys at 0.8 of gestation reproduces endocrine, biophysical, and biochemical changes similar to those measured during spontaneous, term labor in the pregnant monkey. In the pregnant baboon, the spontaneous onset of labor at term has been attributed to a forward shift in the nocturnal estradiol surge relative to that of progesterone in maternal plasma. This study investigated whether androstenedione treatment of the pregnant baboon at 0.7-0.8 of gestation promotes a premature forward shift in the nocturnal surge of maternal plasma estradiol relative to progesterone and whether this shift is associated with premature increases in nocturnal myometrial activity. Eight pregnant baboons were prepared surgically under general anesthesia with vascular catheters and myometrial electromyogram electrodes between 121 and 139 days of gestation (term is ca. 185 days). Catheters were maintained patent by continuous infusion of heparinized saline from the time of surgery until one of two treatments began following at least 9 days of postoperative recovery. In four baboons (Group I), the saline administration was replaced by a continuous infusion of 10% intralipid vehicle during Day 1 of the experimental protocol. During Day 2 and Day 3, the intralipid infusion was switched for a continuous infusion of androstenedione dissolved in intralipid set at a low (0.8 mg x kg(-1) x h(-1)) and at a high (1.6 mg x kg(-1) x h(-1)) dose, each delivered for 24 h. The other four pregnant baboons (Group II) received 10% intralipid vehicle for Days 1, 2, and 3 of the experimental protocol. One baboon from Group I received an additional dose of 0.4 mg x kg(-1) x h(-1) for 24 h before the low and the high dose of androstenedione. In each baboon, during each experimental day, maternal arterial blood samples (1 ml) were taken at 1 h intervals for 12 h, starting 3 h before the onset of darkness in the animal's environment, for measurement of maternal plasma estradiol and progesterone concentrations via RIA. Myometrial contractions were counted during each night-time period of the experimental protocol. All pregnant baboons demonstrated increases in maternal plasma estradiol and progesterone concentrations at night-time. Androstenedione had a dose-dependent effect in elevating day-time maternal plasma estradiol concentrations and in promoting a forward shift in the nocturnal surge of maternal plasma estradiol without affecting the nocturnal progesterone profile in maternal plasma. Maternal treatment with androstenedione also led to an increase in nocturnal myometrial contraction activity. We conclude that androstenedione treatment of the pregnant baboon at 0.7-0.8 of gestation promotes a premature forward shift in the nocturnal estradiol surge relative to that of progesterone in maternal plasma and that this shift is associated with an increase in nocturnal myometrial contraction activity, in a similar way to that measured during spontaneous onset of labor at term in this species.

Androstenedione Treatment of Pregnant Baboons at 0.7-0.8 of Gestation Promotes a Premature Forward Shift in the Nocturnal Maternal Plasma Estradiol Surge Relative to Progesterone and Increases Myometrial Contraction Activity

Androstenedione Treatment of Pregnant Baboons at 0.7-0.8 of Gestation Promotes a Premature Forward Shift in the Nocturnal Maternal Plasma Estradiol Surge Relative to Progesterone and Increases Myometrial Contraction Activity

Maternal intravenous administration of long chain n-3 polyunsaturates to the pregnant ewe in late gestation results in specific inhibition of prostaglandin h synthase (PGHS) 2, but not PGHS1 and oxytocin receptor mRNA in myometrium during betamethasone-induced labor

Both the onset of labor and time to delivery during betamethasone-induced delivery are delayed by omega-3 polyunsaturated fatty acid (PUFA) administration to pregnant sheep. That fatty acid also inhibits the labor-related increase in maternal plasma estradiol and maternal and fetal prostaglandin E(2). To evaluate the mechanism of inhibition of prostaglandin production and delay of onset of labor and time of delivery in PUFA-treated sheep, we determined the effect of PUFA on myometrial prostaglandin H synthase (PGHS) 1 and 2 and oxytocin receptor mRNA levels in betamethasone-induced labor. At 124 days' gestation, a 20% emulsion of either intralipid (IL, n = 6) or PUFA (n = 6) was infused continuously (3 mL/kg per day) intravenously (IV) to the ewe. At 125 days' gestation, betamethasone was administered IV (10 microg/h over 48 hours) to fetuses of both intralipid- and PUFA-treated ewes. Myometrium was collected at necropsy either during betamethasone-induced labor as evaluated by myometrial electromyography or within 5 days of the termination of betamethasone infusion, if delivery did not occur after fetal betamethasone infusion. Total myometrial RNA was analyzed by Northern blot for oxytocin receptor and PGHS1 and 2 mRNA normalized for 18s. Treatment with PUFA decreased myometrial PGHS2 mRNA but did not alter myometrial PGHS1 and oxytocin receptor mRNA after betamethasone administration. This finding provides a mechanism whereby PUFA delays betamethasone-induced delivery in sheep and suggests a potential role of PUFA as an effective tocolytic agent in human pregnancy.

Level of postoperative analgesia is a critical factor in regulation of myometrial contractility after laparotomy in the pregnant baboon: Implications for human fetal surgery

Objectives: We used 2 dosage levels of postoperative opioid administration to determine whether the degree of postoperative analgesia after laparotomy during the last third of baboon pregnancy alters maternal pituitary-adrenal function, androgen secretion, and placental estrogen production. We also determined the relationship of estrogen production to surgery-induced increase in myometrial contraction activity. Study Design: After laparotomy under halothane general anesthesia at 0.75 gestation, 10 pregnant baboons were administered intra-arterially either a normal dose or a double dose of the opioid analgesic buprenorphine for 48 hours. Maternal plasma samples for steroid hormone and oxytocin analyses were obtained at circadian time 1000 hours and at circadian time 1800 hours, 4 hours before and 4 hours after the lights went off, respectively. Myometrial electromyographic contraction activity was quantified for the 6 hours from circadian time 1100 hours to circadian time 1700 hours. Results: Maternal plasma cortisol and dehydroepiandrosterone sulfate concentrations were lower in the dark period (at circadian time 1800 hours) than during daylight (at circadian time 1000 hours) in the double-dose group but not the normal dose group. In contrast, maternal plasma estradiol level was higher at circadian time 1800 hours than at circadian time 1000 hours in the normal dose group but not in the double-dose group. Maternal plasma estrogen level was higher during the hours of darkness in the normal dose group than in the double-dose group. Furthermore the number of myometrial contractions around the onset of darkness was greater in the normal dose group than in the double-dose group. Conclusions: The double dose of analgesia results in lower maternal nighttime plasma estradiol concentrations and significantly less nocturnal contraction activity. These observations further confirm an association between increased maternal plasma estrogen concentrations and increased myometrial contractility in the nonhuman primate. In addition, they suggest that adjustment of the level of postoperative analgesia may be of importance in preventing premature labor after chuman intrauterine fetal surgery. (Am J Obstet Gynecol 1999;180:1196-201.)

Delay of preterm delivery in sheep by omega-3 long-chain polyunsaturates.

A positive correlation has been shown between dietary intake of long-chain omega-3 fatty acids in late pregnancy and gestation length in pregnant women and experimental animals. To determine whether omega-3 fatty acids have an effect on preterm labor in sheep, a fish oil concentrate emulsion was continuously infused to six pregnant ewes from 124 days gestational age. At 125 days, betamethasone was administered to the fetus to produce preterm labor. Both the onset of labor and the time of delivery were delayed by the fish oil emulsion. Two of the omega-3-infused ewes reverted from contractions to nonlabor, an effect never previously observed for experimental glucocorticoid-induced preterm labor in sheep. Maternal plasma estradiol and maternal and fetal prostaglandin E2 rose in control ewes but not in those infused with omega-3 fatty acid. The ability of omega-3 fatty acids to delay premature delivery in sheep indicates their possible use as tocolytics in humans. Premature labor is the major cause of neonatal death and long-term disability, and these studies present information that may lead to a novel therapeutic regimen for the prevention of preterm delivery in human pregnancy.

Relationship between androstenedione-induced myometrial contractions and platelet-activating factor acetylhydrolase in late gestation in pregnant rhesus monkeys.

An association between platelet-activating factor (PAF) and myometrial contractions has been established. Estrogens regulate PAF activity via reduction in the activity of plasma PAF acetylhydrolase (PAF-AH), the enzyme that catalyzes PAF inactivation. Administration of androstenedione to pregnant monkeys leads to sustained increases in maternal plasma estradiol (E2), with persistent nocturnal myometrial contractions. The present study tested the hypothesis that androstenedione-induced contractions are associated with a fall in maternal plasma PAF-AH activity in monkeys. Eight monkeys (132-136 days gestation, dGA) were instrumented under halothane anesthesia with maternal vascular catheters and uterine electromyogram electrodes. At 138-142 dGA, two baseline maternal arterial samples were taken for E2 and PAF-AH measurements. The following day a continuous i.v. androstenedione infusion was started in 4 monkeys while 4 control monkeys received i.v. infusions of vehicle alone. Arterial blood sampling was repeated 1 and 3 days after the start of either infusion. Despite an increase in maternal E2 to term levels and established myometrial contractions, no change in maternal plasma PAF-AH activity occurred after androstenedione treatment. Maternal plasma E2, PAF-AH activity, and contractions remained unchanged from baseline in control monkeys. In conclusion, androstenedione-induced increases in maternal plasma E2 and myometrial contractions are not associated with a fall in maternal plasma PAF-AH specific activity.

Daily and hourly temporal association between Δ 4-androstenedione - induced preterm myometrial contractions and maternal plasma estradiol and oxytocin concentrations in the 0.8 gestation rhesus monkey

OBJECTIVE: Our purpose was to investigate the temporal relationship between Δ 4-androstenedione-induced preterm switching of myometrial activity patterns from contractures to contractions and maternal plasma estradiol and oxytocin concentrations in the 0.8 gestation rhesus monkey. STUDY DESIGN: Eight rhesus monkeys (132 to 136 days' gestation) were instrumented under halothane with femoral artery and vein catheters and uterine electromyogram electrodes. At 138 to 142 days' gestation baseline maternal femoral artery blood samples for estradiol and oxytocin measurement were taken at 30-minute intervals for 7 hours, starting 2 hours before the onset of darkness. The day after baseline sampling a continuous intravenous Δ 4-androstenedione infusion (0.3 mg · kg -1 · hr -1 in 10% intralipid at 0.25 ml · hr -1) was started in four monkeys, while four monkeys were infused intravenously with intralipid alone. The sampling regimen was then repeated at 1 and 3 days after the start of the Δ 4-androstenedione or intralipid infusion. Contractions were counted and estradiol and oxytocin were measured by radioimmunoassay. RESULTS: Androstenedione promoted a premature nocturnal increase in myometrial contractions in conjunction with an increase in maternal plasma concentrations of estradiol and oxytocin, which were of similar magnitude to those measured in spontaneous term labor. The increase in maternal estradiol preceded the increase in maternal oxytocin levels and myometrial contractions. The onset of the increase in maternal plasma oxytocin was closely associated with the appearance of myometrial contractions after Δ 4-androstenedione treatment. In contrast, no sustained premature contractions or changes in estradiol and oxytocin occurred in intralipid-treated monkeys. CONCLUSIONS: We conclude that in the 0.8 gestation rhesus monkey (1) the increase in maternal plasma estradiol precedes the increase in maternal plasma oxytocin after Δ 4-androstenedione treatment and (2) Δ 4-androstenedione-induced preterm myometrial contractions are closely associated in time with physiologic increases in maternal plasma oxytocin concentrations. (A M J O BSTET G YNECOL 1996;174:1050-5.)

The aromatase inhibitor 4-hydroxyandrostenedione (4OHA) prevents androstenedione (A)-induced myometrial (MYO) contractions and increases in maternal plasma estradiol (E2) in pregnant monkeys.

The aromatase inhibitor 4-hydroxyandrostenedione (4OHA) prevents androstenedione (A)-induced myometrial (MYO) contractions and increases in maternal plasma estradiol (E2) in pregnant monkeys.

Effect of androstenedione administration on the maternal hypothalamo-pituitary-adreno-placental axis in the pregnant rhesus monkey.

To assess the interaction among androgens, placenta, and the hypothalamo-pituitary-adrenal axis we studied effects of androstenedione administered intravascularly to the pregnant monkey on maternal plasma CRH, ACTH, dehydroepiandrosterone sulfate (DHEAS), cortisol, and estradiol concentrations. Ten monkeys (128 +/- 3 days gestation; mean +/- SEM) were instrumented under general halothane anesthesia with maternal femoral artery and venous catheters and uterine electromyogram electrodes. At 137-144 days gestation, baseline maternal femoral artery samples for CRH, ACTH, DHEAS, cortisol, and estradiol measurements were taken at 1.5-h intervals for 7 h starting 2 h before darkness. On the following day, a continuous iv androstenedione infusion (0.3 mg/kg.min at 0.25 ml/h) in 10% intralipid was started at 0930 h in four monkeys; the other six animals received vehicle alone at the same rate starting at the same time. Maternal blood sampling was repeated 1 and 3 days after androstenedione or vehicle administration. Maternal plasma CRH, ACTH, DHEAS, cortisol, and estradiol levels were unaffected by intralipid. In contrast, androstenedione infusion produced a sustained increase in maternal plasma estradiol and a sustained fall in maternal plasma ACTH, but did not affect maternal plasma CRH, DHEAS, or cortisol concentrations. These results provide evidence for negative feedback regulation by androgens at the hypothalamo-pituitary-adrenal axis in the pregnant monkey. Lack of inhibition of maternal plasma CRH after androstenedione administration supports differential regulation of hypothalamic and placental CRH by androgens.

Effect of androstenedione administration on the maternal hypothalamo- pituitary-adreno-placental axis in the pregnant rhesus monkey

To assess the interaction among androgens, placenta, and the hypothalamo-pituitary-adrenal axis we studied effects of androstenedione administered intravascularly to the pregnant monkey on maternal plasma CRH, ACTH, dehydroepiandrosterone sulfate (DHEAS), cortisol, and estradiol concentrations. Ten monkeys (128 +/- 3 days gestation; mean +/- SEM) were instrumented under general halothane anesthesia with maternal femoral artery and venous catheters and uterine electromyogram electrodes. At 137-144 days gestation, baseline maternal femoral artery samples for CRH, ACTH, DHEAS, cortisol, and estradiol measurements were taken at 1.5-h intervals for 7 h starting 2 h before darkness. On the following day, a continuous iv androstenedione infusion (0.3 mg/kg.min at 0.25 ml/h) in 10% intralipid was started at 0930 h in four monkeys; the other six animals received vehicle alone at the same rate starting at the same time. Maternal blood sampling was repeated 1 and 3 days after androstenedione or vehicle administration. Maternal plasma CRH, ACTH, DHEAS, cortisol, and estradiol levels were unaffected by intralipid. In contrast, androstenedione infusion produced a sustained increase in maternal plasma estradiol and a sustained fall in maternal plasma ACTH, but did not affect maternal plasma CRH, DHEAS, or cortisol concentrations. These results provide evidence for negative feedback regulation by androgens at the hypothalamo-pituitary-adrenal axis in the pregnant monkey. Lack of inhibition of maternal plasma CRH after androstenedione administration supports differential regulation of hypothalamic and placental CRH by androgens.

Temporal relationship between androstenedione (4A)-induced, preterm myometrial contractions and maternal plasma estradiol (E2) and oxytocin (OT) in rhesus monkeys

Temporal relationship between androstenedione (4A)-induced, preterm myometrial contractions and maternal plasma estradiol (E2) and oxytocin (OT) in rhesus monkeys

Effect of a 48-hour intravenous Δ 4-androstenedione infusion on the pregnant rhesus monkey in the last third of gestation: Changes in maternal plasma estradiol concentrations and myometrial contractility

Increased myometrial activity in the pregnant rhesus monkey occurs in situations in which plasma estrogen concentrations are elevated. Examples of such situations are after laparotomy, with or without hysterotomy, and before delivery. The increased activity occurs primarily in the hours of darkness. To investigate the possibility of a causal relationship between the rise in estrogens and myometrial activity, we infused androstenedione intravenously for 48 hours to the rhesus monkey in the last third of gestation. Myometrial activity was quantified either as an increase in the number of individual contraction events or as a change in the power spectrum at high frequencies characteristic of contractions. Androstenedione infusion was followed by increased myometrial activity. Maternal plasma 17 beta-estradiol concentration was significantly elevated at 10 AM on the second day of androstenedione infusion. We conclude that, in the rhesus monkey late in gestation, estradiol may play a role in the regulation of the contraction activity observed during the hours of darkness in several different situations.

Endocrine Changes during 48 Hours of Food Withdrawal in the Pregnant Rhesus Monkey in the Last Third of Gestation*

We studied the hormonal responses in four pregnant rhesus monkeys between 112 and 149 days gestation. After 2 days, during which the monkeys were fed ad libitum, their food was withdrawn at 1500 h for 48 h while allowing free access to water. The food then was returned, and the animals were studied for a further 2 days. The mean maternal whole blood glucose concentration significantly decreased, and plasma cortisol and dehydroepiandrosterone sulfate (DHEAS) concentrations significantly increased within 30 h of food withdrawal (P less than 0.05). The maternal plasma estradiol concentration increased significantly at 1000 h on the second day of food withdrawal (P less than 0.05), whereas the plasma progesterone concentration did not change. The maternal blood glucose and plasma cortisol, DHEAS and estradiol concentrations returned to baseline by the second day of food replacement. We conclude that the stress of hypoglycemia and/or the attendant inability to eat, together or separately, stimulate maternal adrenal glucocorticoid and androgen secretion during the period of food withdrawal. The increased maternal DHEAS and perhaps other adrenal androgen concentrations result in increased maternal estrogen production.