Hormonal profile and glucose tolerance in late pregnancy and postpartum

Oral glucose tolerance, plasma insulin and basal levels of glucagon, hGH, hPRL, hPL, TSH, T4, T3, thyroxine-binding globulin (TBG), cortisol, corticosteroid-binding globulin (CBG) and estriol were measured in 23 normal pregnant women in late gestation (31 +/- 0.4 weeks of pregnancy). Twelve of these subjects could be re-examined 14 +/- 2 weeks postpartum. Blood glucose was lower basal and after glucose load (100 g) in the pregnant group. Fasting plasma insulin and glucose-induced insulin release were higher in pregnancy. The insulinogenic index and the beta cell response were significantly greater antepartum, while peripheral insulin activity was unchanged. The insulin:glucagon ratio as well as TSH and hGH showed no significant differences between ante- and postpartum values. However, T4, T3, TBG, cortisol, CBG, estriol, hPRL and hPL were significantly higher during gestation than after delivery. T4:TBG and T3:TBG ratios were much lower antepartum, while the cortisol:CBG ratio was comparable ante- and postpartum. To our knowledge this is the first report in which such an extensive hormonal and metabolic analysis was performed in the same women ante- and postpartum. It could be shown that glucose tolerance is not worsened during pregnancy in healthy subjects. The higher gestational insulin values are discussed with respect to the various significant hormonal changes.     

Glycosylated haemoglobin concentrations in mothers of large babies.

Mothers who have big babies may have had abnormal glucose tolerance during pregnancy. Glycosylated haemoglobin (HbA1) concentrations were measured on the first or second day after delivery in 50 women who had had babies weighing over the 95th centile for gestational age and in 50 women who had had normal-sized babies (controls). Nine of the mothers of big babies but only one of the controls had an HbA1 concentration above the normal range. All the women had normal glucose tolerance and HbA1 concentrations six weeks after delivery. Measuring HbA1 concentration in the first two days after delivery in mothers of large babies may identify gestational diabetics.     

Changes in osmolality and blood serum ion concentrations in pregnancy

Changes in osmolality and the concentration of cations (Na, K, Ca, Mg) were studied in blood serum of pregnant women from two weeks after conception, throughout the whole pregnancy, and within the first week after delivery. Altogether 239 women from 18 to 40 years of age were studied. Blood serum osmolality decreased from 287±0.8 to 278±1.6 mOsm/kg H₂O from the fifth week of pregnancy and remained virtually at this level until the end of pregnancy. Hyponatremia was found during the three trimesters of pregnancy, in trimesters II and III hypokalemia was not observed, whereas hypocalcemia and hypomagnemia were found. On the first day after delivery, the blood serum osmolality and concentrations of magnesium ions returned to their levels in nonpregnant women, whereas concentrations of sodium and calcium ions remained decreased. No correlation was found between hypoosmia and changes in blood serum concentrations of ions under study during the three trimesters of pregnancy. Thus, in normal pregnancy, hypoosmia develops from the fifth week after conception and persists until delivery. The concentrations of sodium, potassium, calcium, and magnesium ions are regulated by independent mechanisms to provide retention of these parameters within certain periods of pregnancy at the level of nonpregnant women on the background of hypoosmia.     

Pregnancy alters cortisol feedback inhibition of stimulated ACTH: studies in adrenalectomized ewes

These studies test the hypothesis that pregnancy alters the feedback effects of cortisol on stimulated ACTH secretion. Ewes were sham-operated (Sham), or adrenalectomized (ADX) at approximately 108 days gestation and replaced with aldosterone (3 microg x kg(-1) x day(-1)) and with cortisol at either of two doses (ADX + 0.6 and ADX + 1 mg x kg(-1) x day(-1)); ewes were studied during pregnancy and postpartum. Mean cortisol levels produced in ADX ewes were similar to normal pregnant ewes (ADX+1) or nonpregnant ewes (ADX+0.6), respectively. Plasma ACTH concentrations in response to infusion of nitroprusside were significantly increased in the pregnant ADX+0.6 ewes (1,159 +/- 258 pg/ml) relative to pregnant Sham ewes (461 +/- 117 pg/ml) or the ADX+1 ewes (442 +/- 215 pg/ml) or the same ewes postpartum (151 +/- 69 pg/ml). Plasma ACTH concentrations were not significantly different among the groups postpartum. Increasing plasma cortisol to 20-30 ng/ml for 24 h before hypotension produced similar inhibition of ACTH in all groups. Pregnancy appears to decrease the effectiveness of low concentrations of cortisol to inhibit ACTH responses to hypotension.     

Plasma lipids and apolipoproteins A and B in human pregnancy

A cross sectional study was carried out in 200 normal pregnant women between 8-40th weeks of gestation, 25 women during delivery and 25 women 6 weeks after delivery. Plasma and lipoprotein lipids were measured using standard procedures. Apolipoprotein A (Apo A) and Apolipoprotein B (Apo B), were measured by electroimmunoassay. Plasma levels of Apo A were elevated in pregnant women but the elevations were not significant until 17-20 weeks of gestation. Apo A during pregnancy was significantly correlated (p less than 0.001) with high density lipoprotein cholesterol (HDL-C). The level of Apo B increased progressively during pregnancy and it was significantly correlated (p less than 0.001) with total cholesterol (TC), plasma triglycerides (TG) and phospholipids (PL). Apo A and Apo B levels returned to non pregnant values within the puerperium, whereas TC, TG and PL remained significantly elevated above controls (p less than 0.01) 6 weeks post partum.     

Effect of breast-feeding on pituitary-ovarian function after childbirth

Pituitary and ovarian function at the end of pregnancy and during the first six weeks after delivery was investigated serially in women who fully breast-fed their infants and in women who did not. In the women who did not breast-feed the plasma prolactin level decreased rapidly and from the third day after delivery was significantly lower than in the breast-feeding mothers, reaching the normal range of the menstrual cycle by the third week of the puerperium. In the breast-feeding mothers the plasma prolactin was still raised six weeks after delivery. The levels of FSH in both groups were identical and increased over the third week of the puerperium. Plasma oestrogen fell steeply in both groups during the first two weeks after delivery. In the breast-feeding mothers plasma oestrogen remained depressed but increased in the non-lactating women, reflecting follicular development in the ovary in response to FSH; the plasma oestrogen levels were significantly higher in the non-lactating women from the 17th day of the puerperium onwards. These findings support the concept that in breast-feeding women prolactin delays the return of ovulation by inhibiting the ovarian response to FSH stimulation.     

Endocrine changes during pregnancy, parturition and the early post-partum period in the llama (Lama glama)

Mean (+/- s.d.) pregnancy length for the 14 llamas in this study was 350 +/- 4.5 days. Plasma progesterone concentrations increased by 5 days after mating and remained elevated (greater than 2.0 ng/ml) throughout most of pregnancy. At about 2 weeks before parturition, plasma progesterone concentrations began to decline, dropped markedly during the final 24 h before parturition, and returned to basal concentrations (less than 0.5 ng/ml) by the day of parturition. The combined oestrone + oestradiol-17 beta and oestradiol-17 beta concentrations varied between 6 and 274 pg/ml and 4 and 114 pg/ml, respectively, during the first 9 months of pregnancy. Concentrations increased between 9 months after mating and the end of pregnancy with peak mean concentrations of 827 +/- 58 (s.e.m.) pg oestrone + oestradiol-17 beta/ml (range: 64-1658) and 196 +/- 10 pg oestradiol-17 beta/ml (31-294) during the last week of pregnancy. Concentrations then declined to 87 +/- 14 pg oestrone + oestradiol-17 beta/ml (7-488) and 25 +/- 5 pg oestradiol-17 beta/ml (2.5-142) during the first week post partum. Plasma cortisol concentrations varied between 2.6 and 51.9 ng/ml (14.0 +/- 0.5) from mating until 2 weeks before parturition when the concentrations began to decline. Only a slight increase in plasma cortisol concentrations was observed in association with parturition. Plasma triiodothyronine concentrations varied between 0.5 and 4.5 ng/ml (1.9 +/- 0.1) throughout pregnancy and the periparturient period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Course of pregnancies in women with Cushing's disease treated by gamma-knife

Data concerning pregnancy in women with Cushing's disease treated by gamma-knife (GK) are scanty. We present and discuss the course and outcome of five pregnancies in two women with Cushing's disease (CD), the first of whom was treated only by GK, and the second one treated by surgery, GK and ketoconazole. In the first patient, pregnancy was uneventful and full-term. During gestation, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were steady, and always in the normal range for healthy non-pregnant individuals. The newborn was healthy and normal-weight. In the second woman, two pregnancies, occurring 3 years after GK and few months after ketoconazole withdrawal, were interrupted by spontaneous abortion or placental disruption despite normal cortisol levels. This patient became again pregnant 3 years later and delivered vaginally a healthy full-term infant. Seven months after the delivery, the patient became pregnant again and at the 39th week of gestation delivered vaginally a healthy male. Hypoprolactinemia and/or central hypothyroidism occurred in both cases. In women with CD treated by GK, pregnancy can occur. However, pregnancy is at risk even when ACTH and cortisol levels are normalized by treatment. After GK, evaluation of pituitary function is mandatory due to the risk of hypopituitarism.     

Pregnancy in diabetic women: outcome with a program aimed at normoglycemia before meals.

A program designed to achieve normal plasma glucose concentrations before meals was tested in 83 insulin-dependent diabetic women during 110 pregnancies. The women rigidly controlled their carbohydrate intake but not their total energy intake, and twice daily they injected a combination of short-acting (Toronto) and intermediate-acting (NPH or Lente) insulin. Obstetric care was highly individualized and was aimed at avoiding or minimizing the impact of complications, such as hypertension, on the fetus and ensuring fetal lung maturity before delivery. The mean plasma glucose levels before meals (+/- standard error of the mean) were 136 +/- 9, 117 +/- 5 and 101 +/- 2 mg/dl during the first, second and third trimesters respectively. Obstetric complications included hypertensive disease of pregnancy (in 30.0%) and hydramnios (in 16.4%). The mean gestational age (+/- standard deviation [SD]) was 38.1 +/- 1.8 weeks, the cesarean section rate 45.4% and the mean stay in hospital for diabetes control before delivery (+/- SD) 15.7 +/- 9.6 days. The perinatal mortality rate was 0.9%. Neonatal problems included congenital anomalies in 3.6%, somatomegaly in 24.6%, hypoglycemia in 26.5%, hypocalcemia in 17.3% and hyperbilirubinemia in 39.4%. There were nine cases (8.2%) of the respiratory distress syndrome, four (3.6%) of which were severe. These findings lend support to the importance of a policy aimed at achieving normoglycemia and fetal lung maturity before delivery, goals that are attainable without lengthy antenatal hospitalization.     

Whole body protein kinetics in women: effect of pregnancy and IDDM during anabolic stimulation

The effects of pregnancy and type 1 diabetes [insulin-dependent diabetes mellitus (IDDM)] on protein metabolism are still uncertain. Therefore, six normal and five IDDM women were studied during and after pregnancy, using [(13)C]leucine and [(2)H(5)]phenylalanine with a hyperinsulinemic-euglycemic clamp and amino acid infusion. Fasting total plasma amino acids were lower in pregnancy in normal but not IDDM women (2,631 +/- 427 vs. 2,057 +/- 471 and 2,523 +/- 430 vs. 2,500 +/- 440 micromol/l, respectively). Whole body protein breakdown (leucine) increased in pregnancy [change in normal (delta N) and IDDM women (delta D) 0.59 +/- 0.40 and 0.48 +/- 0.26 g. kg(-1). day(-1), both P < 0.001], whereas reductions in protein breakdown due to insulin/amino acids (delta N -0.57 +/- 0.19, delta D -0.58 +/- 0.20 g. kg(-1). day(-1), both P < 0.001) were unaffected by pregnancy. Protein breakdown in IDDM women was not higher than normal, and neither pregnancy nor type 1 diabetes altered the insulin sensitivity of amino acid turnover. Nonoxidized leucine disposal (protein synthesis) increased in pregnancy (delta N 0.67 +/- 0.45, delta D 0.64 +/- 0.34 g. kg(-1). day(-1), both P < 0.001). Pregnancy reduced the response of phenylalanine hydroxylation to insulin/amino acids in both groups (delta N -1.14 +/- 0.74, delta D -1. 12 +/- 0.77 g. kg(-1). day(-1), both P < 0.05). These alterations may enable amino acid conservation for protein synthesis and accretion in late pregnancy. Well-controlled type 1 diabetes caused no abnormalities in the regulation of basal or stimulated protein metabolism.     

How to diagnose and manage Cushing's disease during pregnancy, when hypercortisolism is mild?

Diagnosis of mild Cushing's disease (CD) can be difficult in pregnant women, because its clinical and biochemical features can be erroneously interpreted as consequence of the gestation. Corticotropin releasing hormone (CRH) and desmopressin (DDAVP) tests are currently used to confirm CD, but data concerning adrenocorticotropic hormone (ACTH) response during pregnancy are lacking. A woman with mild cushingoid features was evaluated during the first trimester of gestation. Serum cortisol was normal at morning, but increased at midnight and incompletely suppressed by 1-mg dexamethasone overnight administration. Also 24-h urinary free cortisol levels were mildly elevated. She delivered vaginally a healthy newborn at the 39th week of an uneventful pregnancy. After delivery, an ACTH-secreting microadenoma was surgically removed. During the first trimester of gestation and after delivery, human CRH (h-CRH) and DDAVP-stimulated ACTH peaks were higher than those measured in 22 healthy premenopausal women. While the ACTH/h-CRH peak was intermediate between those measured in the healthy women and in 9 CD female patients, ACTH/DDAVP peak was in the range of CD patients and dramatically higher than those of healthy women. However, ACTH increase after h-CRH was significantly higher after delivery than during gestation (p?相似文献   

Influence of repeated regrouping on reproduction in gilts

It is generally assumed that stress around oestrus and during early pregnancy reduces reproductive performance of pigs. In our experiment, late prepuberal gilts (age at arrival 225+/-6 days) were housed in groups of four. Stress treatment consisted of once weekly regrouping and twice weekly feed competition of the 28 Stress gilts during 6 consecutive weeks, starting 13 days after arrival. Control gilts (n=28) were not treated. During the 0.5-1.5h after regroupings, Stress animals fought consistently more than the Control animals; up to 13 of the Stress animals fought for at most 60% of the time compared to one Control animal fighting for at most 3.3% of the time. The day before first regrouping, gilts had on average 4.0+/-0.9 skin scratches. By week 6, this number had reduced to 2.1+/-1.0 in Control, but remained 4.0+/-1.3 in Stress gilts (P<0.05). In the afternoon after regroupings, skin scratches increased up to 6.3+/-1.6 in the Stress gilts. Saliva cortisol in the afternoon before regrouping did not differ between weeks 1, 3 and 6, nor did it differ between Stress and Control. In Stress gilts, saliva cortisol was increased in the afternoon of first regrouping, in Batch 2 only (from 1.8+/-0.4 to 4.1+/-0.9 ng/ml; P<0.05). Animals showing a second oestrus within 5 weeks after arrival were inseminated. Duration of second oestrus of these animals was 2.48+/-0.66 days in the Stress gilts (n=24) and 2.21+/-0.58 days in the Control gilts (n=22; P>0.10). At Day 35 after insemination, pregnancy rate was 100% in both groups. Ovulation rate and number of total and vital fetuses was similar (P>0.10). The Stress treatment during a 6-week period around insemination consistently resulted in fighting but did not result in long term effects on cortisol levels and did not impair reproductive performance.     

Free and phospholipid-bound choline concentrations in serum during pregnancy,after delivery and in newborns

The aims of this study were to determine whether serum free choline and phospholipid-bound choline concentrations change during the pregnancy or after childbirth and to determine if the serum choline concentrations of the mother and newborn are correlated. Serum free and bound choline concentrations were 10.7 +/- 0.5 microM and 2780 +/- 95 microM in control, non-pregnant women, and rose significantly (p < 0.001) to 14.5 +/- 0.6 microM and 3370 +/- 50 microM or to 16.5 +/- 0.7 microM and 3520 +/- 150 microM after 16-20 weeks or 36-40 weeks of pregnancy, respectively. Serum free and phospholipid-bound choline fell by 14-22% (p < 0.05-01) after either vaginal delivery or caesarian section, and remained low (by 15-42%; p < 0.05-0.001) for 12 h and then rose toward the baseline within 24 h. In amniotic fluid, free choline and phospholipid-bound choline concentrations were 22.8 +/- 1.0 and 19.6 +/- 0.8 microM or 24.0 +/- 1.5 and 516 +/- 43 microM at 16-20 weeks of gestational age or at term, respectively. In newborns, serum free choline concentrations were higher (p < 0.001) and phospholipid-bound choline concentrations were lower (p < 0.001) than in their mothers. These results show that serum free choline and phospholipid-bound choline concentrations are elevated during the pregnancy, which may be required for an adequate maternal supply of choline to the fetus. These observations are clinically important to determine the ideal dietary intake of choline during the pregnancy.     

Pregnancy and the risk of autoimmune disease

Autoimmune diseases (AID) predominantly affect women of reproductive age. While basic molecular studies have implicated persisting fetal cells in the mother in some AID, supportive epidemiological evidence is limited. We investigated the effect of vaginal delivery, caesarean section (CS) and induced abortion on the risk of subsequent maternal AID. Using the Danish Civil Registration System (CRS) we identified women who were born between 1960 and1992. We performed data linkage between the CRS other Danish national registers to identify women who had a pregnancy and those who developed AID. Women were categorised into 4 groups; nulligravida (control group), women who had 1st child by vaginal delivery, whose 1st delivery was by CS and who had abortions. Log-linear Poisson regression with person-years was used for data analysis adjusting for several potential confounders. There were 1,035,639 women aged >14 years and 25,570 developed AID: 43.4% nulligravida, 44.3% had their first pregnancy delivered vaginally, 7.6% CS and 4.1% abortions. The risk of AID was significantly higher in the 1st year after vaginal delivery (RR = 1.1[1.0, 1.2]) and CS (RR = 1.3[1.1, 1.5]) but significantly lower in the 1st year following abortion (RR = 0.7[0.6, 0.9]). These results suggest an association between pregnancy and the risk of subsequent maternal AID. Increased risks of AID after CS may be explained by amplified fetal cell traffic at delivery, while decreased risks after abortion may be due to the transfer of more primitive fetal stem cells. The increased risk of AID in the first year after delivery may also be related to greater testing during pregnancy.     

The nonsuppressibility of plasma cortisol persists after pregnancy

To determine if normal balance is restored to the hypothalamic-pituitary-adrenal axis after pregnancy, we compared the dexamethasone suppressibility of plasma cortisol in women four days after delivery of their infant, with that of nonpregnant women. Plasma concentrations of cortisol before dexamethasone administration were similar in the post-partum women and in women taking oestrogen contraceptives, but both were higher than in normally cycling women. After dexamethasone, plasma cortisol in the post-partum women was significantly higher than in both oestrogen-taking and normally cycling nonpregnant women. The reduced dexamethasone-suppressibility of plasma cortisol, which is characteristic of pregnancy, extends into the post-partum period.     

Induction of premature delivery in sheep following infusion of cortisol to the fetus. I. The effect of maternal administration of progestagens

Premature induction of delivery in fetuses infused with graded doses of cortisol was brought about in 123.5 +/- 7.7 h (mean +/- SEM, n = 6) after the start of cortisol infusion. This treatment caused a rise in fetal plasma cortisol similar to that observed at normal delivery. Maternal and fetal progesterone and 20 alpha-dihydroprogesterone concentrations decreased to basal levels during infusion of cortisol to the fetus. Induction of premature delivery was delayed or prevented by concomitant treatment of the ewe with progestagen. Maternal intramuscular injection of 100 mg progesterone, 2 times daily, prevented delivery in four of four ewes treated during the time that cortisol was infused into the fetus (11-13 days). Maternal plasma progesterone and 20 alpha-dihydroprogesterone concentrations were maintained during this period, but fetal plasma progesterone concentrations decreased to the same extent as in the fetuses infused with cortisol alone. A single intramuscular injection of 250 mg of medroxyprogesterone acetate to ewes on the day before commencement of infusion of cortisol to the fetus prevented delivery in four of six ewes during the time that cortisol was infused for 9, 13, 14, and 15 days, respectively. One ewe delivered a live lamb at 133.5 h and another at 147.7 h after the start of infusion of cortisol to the fetus. Maternal and fetal plasma cortisol, progesterone, and 20 alpha-dihydroprogesterone concentrations were similar to those observed during infusion of cortisol alone to the fetus. Although fetal cortisol concentrations rose in a similar fashion, and to a similar extent, in all three groups during infusion of cortisol to the fetus, fetal 11-desoxycortisol concentrations only rose above basal levels close to the time of delivery in cortisol-infused fetuses or, in the progestagen-treated groups, when the fetus showed signs of being stressed.     

Efficacy and long term effects of antenatal prophylaxis with anti-D immunoglobulin.

OBJECTIVE--To measure the safety and efficacy of antenatal treatment with anti-D immunoglobulin. DESIGN--Open study with historical controls. SETTING--Multicentre study in 17 hospitals in West Yorkshire. PATIENTS--1238 Rh negative women who delivered Rh positive infants after 34 weeks in their first pregnancy in 1980-1 (group 1) and 2000 similar primigravidas from 1978-9 (group 2). Obstetric data were collected for 616 women in group 1 who had a subsequent pregnancy, 536 similar women in group 2, and 410 Rh positive but otherwise similar primigravidas who delivered in the same hospitals in 1978-81 (group C). INTERVENTIONS--Anti-D immunoglobulin 100 micrograms intramuscularly was given at 28 and 34 weeks to the mothers in their first pregnancy who delivered in 1980-1. END POINTS--Detection of anti-D antibody in the first or any subsequent pregnancy in groups 1 and 2. For all three groups having subsequent pregnancies gestation at delivery, birth weight, fetal survival at one month, pre-eclampsia defined as blood pressure greater than 140/90 on two occasions more than 12 hours apart, and proteinuria greater than 0.25 milligram. MEASUREMENTS AND MAIN RESULTS--Antenatal immunisation to Rh(D) occurred in six mothers in group 1 and 32 group 2. Most immunisations occurred in the first or second pregnancy. The rates of abortion, gestation at delivery, birth weight, and fetal survival were not significantly different among the three groups. The incidence of pre-eclampsia was lower in mothers given antenatal anti-D immunoglobulin, but the difference was not significant. CONCLUSIONS--Antenatal prophylaxis with anti-D immunoglobulin is effective, and the effect of giving it in the first pregnancy persists into at least the second pregnancy. It seems to be safe for the fetus in the index and subsequent pregnancies.     

QT dispersion and T-loop morphology in late pregnancy and after delivery

The aim of the study was to detect changes of both the QT dispersion and T-loop morphology resulting from the changed spatial position of the heart during pregnancy. Electrocardiographic and vectorcardiographic recordings were obtained from 37 healthy women 19-36 years old in the 36th to 40th week of physiological pregnancy and 2 to 6 days after delivery. The same recordings were obtained from 18 healthy women of the same age. The average QT dispersion (+/- S.D.) in normal subjects was significantly lower (34 +/- 12 ms) than in those in late pregnancy (73 +/- 18 ms) (P < 0.001). The average amplitude of T-loop (Ta) in women in late pregnancy was significantly (P < 0.001) smaller (532 +/- 98 microV) and the width of T-loop (Tw) was wider (21.24 +/- 11.48 deg) than in the control group (793 +/- 114 microV and 7.17 +/- 3.02 deg, respectively). The partial post-partum restoration of all parameters was not significant. In all groups, the QT dispersion was significantly correlated with Tw but not with Ta. According to these results we can conclude that the QT dispersion is an indirect reflection of the complete process of ventricular repolarization, reflected in the morphology of the T-loop.     

Elevated maternal cortisol early in pregnancy predicts third trimester levels of placental corticotropin releasing hormone (CRH): priming the placental clock

The purposes of this study were to determine the intervals when placental corticotrophic-releasing hormone (CRH) was most responsive to maternal cortisol. A sample of 203 women each were evaluated at 15, 19, 25 and 31 weeks gestation and followed to term. Placental CRH and maternal adrenocorticotropin hormone (ACTH), B-endorphin and cortisol were determined from plasma. CRH levels increased faster and were higher in women who delivered preterm compared with women who delivered at term (F3,603 = 5.73, p < .001). Simple effects indicated that CRH levels only at 31 weeks predicted preterm birth (F1,201 = 5.53, p = .02). Levels of cortisol were higher in women who delivered preterm at 15 weeks gestation (F1,201 = 4.45, p = .03) with a similar trend at 19 weeks gestation. Hierarchical regression suggested that the influence on birth outcome of maternal cortisol early in pregnancy was mediated by its influence on placental CRH at 31 weeks. Elevated cortisol at 15 weeks predicted the surge in placental CRH at 31 weeks (R = .49, d.f. = 1,199, Fchange = 61.78, p < .0001). Every unit of change in cortisol (microg/dl) at 15 weeks was associated with a 34 unit change of CRH (pg/ml) at 31 weeks. These findings suggested that early detection of stress signals by the placenta stimulated the subsequent release of CRH and resulted in increased risk for preterm delivery.     

Impaired LH-RH release by estrogen in women with sulpiride-induced hyperprolactinemia

The effects of hyperprolactinemia on the release of immunoreactive luteinizing hormone-releasing hormone (LH-RH) and luteinizing hormone (LH) in response to iv injection of 20 mg conjugated estrogens (Premarin) were studied. Five normal cycling women were injected with Premarin on the morning of the 7th day of the first cycle (control cycle), and then the plasma levels of LH-RH, LH, and prolactin (PRL) were determined every 8 to 16 hours for 72 h. Two months later, the same women received 200 mg of oral sulpiride daily for 8 days from the 3rd day of the cycle (sulpiride treated cycle), and then the same protocol as in the control cycle was applied. Mean (+/- SE) plasma levels of PRL on day 7 in the sulpiride treated cycle were significantly higher than those in the control cycle (118 +/- 24 ng/ml vs. 14 +/- 4 ng/ml, p less than 0.001). After estrogen injection, the mean percent increases in immunoreactive LH-RH at 32 h (control: 71 +/- 38% vs. sulpiride: 6 +/- 36%) and 40 h (154 +/- 38% vs. -5 +/- 21%) and in LH at the 48 h (175 +/- 89% vs. 57 +/- 57%) and 56 h (99 +/- 32% vs. 7 +/- 21%) were significantly (p less than 0.01 or p less than 0.05) suppressed in the sulpiride cycle. These data suggest that the impaired positive feedback effect of estrogen on LH-release in hyperprolactinemic anovulatory women may be caused, at least in part, by disturbed LH-RH release.