Production of urinary 11-keto-thromboxane B2 in normal and hypertensive pregnancies

Urinary levels of 11-keto-thromboxane B2 (11-keto-TXB2), were elevated at all gestational ages (12-41 weeks) compared with non-pregnant levels. 11-keto-TXB2 levels exceeded those of TXB2 throughout pregnancy, which suggested that 11-keto-TXB2 may be the major urinary metabolite of TXA2 in normotensive pregnancy, as in the non-pregnant state. This was reversed in women with mild pregnancy-induced hypertension (P.I.H.), such that urinary levels of TXB2 were higher (p less than 0.01) than those of 11-keto-TXB2. Since the 11-thromboxane dehydrogenase enzyme is found in the placenta, the low levels of 11-keto-TXB2 may be the result of placental damage decreasing the activity of the enzyme. The relationship between these findings and the aetiology of P.I.H. is not clear, but changes in urinary 11-keto-TXB2 may be of use in identifying those women at risk of developing P.I.H.     

Determination of 9 alpha, 11 beta-prostaglandin F2 by stereospecific antibody in various rat tissues

In view of the recent finding that prostaglandin D2 is stereospecifically converted to 9 alpha, 11 beta-prostaglandin F2, an isomer of prostaglandin F2 alpha, a highly specific and sensitive radioimmunoassay for 9 alpha, 11 beta-prostaglandin F2 was developed and applied to determine the content of this prostaglandin in various rat tissues. Antisera against 9 alpha, 11 beta-prostaglandin F2 were raised in rabbits immunized with the bovine serum albumin conjugate, and [3H]9 alpha, 11 beta-prostaglandin F2 was enzymatically prepared from [3H]prostaglandin D2. The assay detected 9 alpha, 11 beta-prostaglandin F2 over the range of 20 pg to 1 ng, and the antiserum showed less than 0.04% cross-reaction with prostaglandin F2 alpha, prostaglandin F2 beta and 9 beta, 11 beta-prostaglandin F2. To avoid postmortem changes, tissues were frozen in liquid nitrogen immediately after removal. The basal level of 9 alpha, 11 beta-prostaglandin F2 was hardly detectable in various tissues of the rat examined, including spleen, lung, liver and brain; although it was found to be 0.31 +/- 0.06 ng/g wet weight in the small intestine. During convulsion induced by pentylenetetrazole, enormous amounts of prostaglandin D2 (ca. 180 ng/g wet weight) and prostaglandin F2 alpha (ca. 70 ng/g) were produced in the brain; however, 9 alpha, 11 beta-prostaglandin F2 was detected neither there nor in the blood. This result demonstrates that the conversion to 9 alpha, 11 beta-prostaglandin F2 is a minor pathway, if one at all, of prostaglandin D2 metabolism in the rat brain.     

Metabolism of prostaglandin D2 in isolated rat lung: the stereospecific formation of 9 alpha,11 beta-prostaglandin F2 from prostaglandin D2

The metabolic transformation of exogenous prostaglandin D2 was investigated in isolated perfused rat lung. Dose-dependent formation (2-150 ng) of 9 alpha,11 beta-prostaglandin F2, corresponding to about 0.1% of the perfused dose of prostaglandin D2, was observed by specific radioimmunoassay both in the perfusate and in lung tissue after a 5-min perfusion. To investigate the reason for this low conversion ratio, we analyzed the metabolites of tritium-labeled 9 alpha,11 beta-prostaglandin F2 and prostaglandin D2 by boric acid-impregnated TLC and HPLC. By 5 min after the start of perfusion, 9 alpha,11 beta-prostaglandin F2 disappeared completely from the perfusate and the major product formed remained unchanged during the remainder of the 30-min perfusion. The major product was separated by TLC and identified as 13,14-dihydro-15-keto-9 alpha,11 beta-prostaglandin F2 by GC/MS. In contrast, pulmonary breakdown of prostaglandin D2 was slow and two major metabolites in the perfusate increased with time, each representing 56% and 11% of the total radioactivity at the end of the perfusion. The major product (56%) was identified as 13,14-dihydro-15-ketoprostaglandin D2 and the minor one (11%) was tentatively identified as 13,14-dihydro-15-keto-9 alpha,11 beta-prostaglandin F2 based on the results from radioimmunoassays, TLC, HPLC, and the time course of pulmonary breakdown. These results demonstrate that the metabolism of prostaglandin D2 in rat lung involves at least two pathways, one by 15-hydroxyprostaglandin dehydrogenase and the other by 11-ketoreductase, and that the 9 alpha,11 beta-prostaglandin F2 formed is rapidly metabolized to 13,14-dihydro-15-keto-9 alpha,11 beta-prostaglandin F2.     

Increased levels of serum macrophage colony-stimulating factor before the onset of preeclampsia.

Macrophage colony-stimulating factor (M-CSF) is known to play a central role in maintaining pregnancy. The present study determined whether the increase in serum M-CSF levels preceded the onset of preeclampsia. Blood was collected from 110 normotensive pregnant women at risk for preeclampsia who were carrying single fetuses at about 30 weeks of gestation. After centrifugation, serum was stored at -20 degrees C until assay. Eighteen women developed preeclampsia at a later stage of pregnancy (group 1), while 88 women continued to have normotensive pregnancies until delivery. Thirty-four of the 88 women with normotensive pregnancy who were matched for age and parity were selected to form a control group (group 2). Serum M-CSF levels were determined by the sandwich ELISA method using three antibodies. Serum level of M-CSF was 1,266 U/ml (median) in group 1 and 1,082 U/ml in group 2. Serum M-CSF levels were significantly higher in group 1 than in group 2 (p < 0.0002). Increased levels of serum M-CSF markedly precede the development of clinical manifestations of preeclampsia. High serum M-CSF levels support M-CSF elevation in the placenta. This elevation at 30 weeks of gestation may be associated with placental hypoxia, which is considered the cause of preeclampsia.     

Plasma levels of the immunomodulatory cytokine interleukin-10 during normal human pregnancy: a longitudinal study

Pregnancy is proposed to be a Th2 phenomenon, where Th2 cytokines inhibit Th1 responses to improve foetal survival. The importance of interleukin-10 (IL-10), an immunomodulatory cytokine produced by Th2 cells, in the maintenance of normal pregnancy is becoming increasingly apparent. In a longitudinal case-control study, the physiological effect of pregnancy on plasma IL-10 was investigated. The plasma concentration of IL-10 was determined using an ELISA technique in 99 pregnant women sampled at 12, 20 and 35 weeks of gestation, 38 non-pregnant control subjects sampled in parallel and in a subgroup of women sampled at 3 days post-partum (n, pregnant 21, non-pregnant 21). Plasma IL-10 was significantly higher in pregnant women at 12, 20 and 35 weeks of gestation (p<0.05, p<0.01 and p<0.0001, respectively), and in mothers post-delivery (p<0.01) when compared to non-pregnant control subjects. Furthermore, there was no significant effect of gestational time on IL-10 concentration. Results from the current study suggest that elevated IL-10 is a physiological consequence of normal healthy pregnancy. These findings help clarify previous conflicting results and establish a range for plasma levels of IL-10 in normal healthy pregnancy.     

The Fern Reaction of Cervical Mucus: Part I. The Effect of the Normal Ovarian Cycle and of Pregnancy. Part II. A Guide to the Early Diagnosis of Pregnancy

The fern reaction of endocervical mucus was tested in 100 non-pregnant and 200 pregnant women with a view to establishing the relationship of this fern pattern to normal ovarian cyclical changes and normal pregnancy. The fern appeared at day 7-9 of the cycle and disappeared at day 18-20. Twenty-eight of 100 pregnancies before 10 weeks yielded positive fern reactions; two of 100 pregnancies after 10 weeks yielded positive fern reactions. In the presence of a positive fern reaction, the administration of 10 mg. of norethynodrel (Enovid) daily for seven days led to prompt withdrawal bleeding in the absence of pregnancy. With a negative fern reaction, a spontaneous period ensues within 12 days in the absence of pregnancy. Two hundred women were tested for early pregnancy on this premise; in 198, a correct diagnosis was obtained.     

The pregnancy-induced increase of plasma angiotensin-(1-7) is blunted in gestational diabetes

BACKGROUND AND OBJECTIVE: It has been shown that the circulating Renin-Angiotensin System (RAS) is activated during normal pregnancy, but little is known about RAS in pregnancies complicated by gestational diabetes (GDM). GDM is considered not merely a temporary condition, but a harbinger of hypertension and type 2 diabetes. The aim of this study was to evaluate the circulating RAS profile in normotensive women with GDM at the third trimester of pregnancy and to compare the results with healthy pregnant and non-pregnant age-matched women. METHODS: The diagnostic criteria for GDM followed the recommendations of the American Diabetes Association. Angiotensin I (Ang I), Angiotensin II (Ang II) and Angiotensin 1-7 [Ang-(1-7)] were determined in 24 pregnant patients with GDM; 12 healthy pregnant women and 12 non-pregnant women by radioimmunoassay. RESULTS: Levels of Ang I, Ang II and Ang-(1-7) were higher in pregnant women (p<0.05), but showed a different pattern in the GDM group, in which reduced Ang-(1-7) circulating levels were found (p<0.05). This observation was confirmed by the significantly lower Ang-(1-7)/Ang I ratio (p<0.05). CONCLUSION: Our data suggest that reduced levels of the vasodilator Ang-(1-7) could be implicated in the endothelial dysfunction seen in gestational diabetic women during and after pregnancy.     

Modification of prostaglandin F-2 alpha synthesis and release in the ewe during the initial establishment of pregnancy

Pregnant (N = 10) and non-pregnant (N = 10) ewes were bled every 2 h from Days 12 to 17 after oestrus (oestrus = Day 0). Plasma concentrations of progesterone, 15-keto-13,14-dihydro-PGF-2 alpha and 11-ketotetranor-PGF metabolites were determined in all samples. The number of PGF-2 alpha pulses in non-pregnant ewes was 8.2 +/- 0.4 (mean +/- s.e.m.) with an interpulse interval of 10.7 +/- 0.7 h. Two or 3 pulses of low frequency (interpulse interval = 13.4 +/- 1.6 h) occurred in most non-pregnant ewes before the onset of luteolysis; the interpulse interval then decreased to 7.9 +/- 0.4 h for the 6.0 +/- 0.3 pulses temporally associated with luteolysis. In contrast, the number of PGF-2 alpha pulses in pregnant ewes was lower (2.5 +/- 0.7, 0-8) and the interpulse intervals longer (18.9 +/- 6.1 h). Most pulses occurred on Days 14 and 15 in the pregnant and non-pregnant ewes. The mean concentrations of both PGF-2 alpha metabolites in non-pregnant ewes were highest on Day 15 while basal levels of both metabolites remained constant at all times. In pregnant ewes, the mean concentrations of both metabolites were highest on Day 14; basal concentrations of both metabolites were also highest on Day 14. The mean concentrations of 15-keto-13,14-dihydro-PGF-2 alpha were higher in pregnant than in non-pregnant ewes on Days 13 and 14 (P less than 0.05) and higher in non-pregnant than pregnant ewes on Day 15 (P less than 0.05). The basal concentrations of the 15-keto metabolite were higher in pregnant than non-pregnant ewes at Days 13, 14, 15, 16 and 17 (P less than 0.05). Both the mean and the basal concentrations of 11-ketotetranor-PGF metabolites were higher in pregnant than in non-pregnant ewes on Day 14 (P less than 0.05). It is concluded that uterine production of PGF-2 alpha peaks at Days 14-15 after oestrus in pregnant and non-pregnant ewes. Patterns of release differ, however, in that non-pregnant ewes have a pulsatile PGF-2 alpha pattern superimposed on a constant baseline, while pregnant ewes have an increasing basal secretory pattern which is more nearly continuous, i.e. not pulsatile in form. Modification of pulsatile PGF-2 alpha synthesis and release is therefore a key aspect of prolongation of luteal function at the beginning of pregnancy in the ewe.     

A longitudinal descriptive study of self-reported abnormal smell and taste perception in pregnant women

Self-reported abnormal sensitivity, qualitative distortions and phantom sensations with respect to smell and taste was assessed with a longitudinal design, based on questions referring to gestational weeks 13-16 and 31-34 of pregnancy in comparison with 9-12 weeks post partum and with non-pregnant women with corresponding time durations and intervals. The results show that abnormal smell and/or taste perception was reported by 76% of the pregnant women, typically believed to be caused by their pregnancy. Increased smell sensitivity was found to be very common at the early stage of pregnancy (67% of all pregnant respondents) and occasionally accompanied by qualitative smell distortions (17%) and phantom smells (14%). The smell abnormalities were less common at the late pregnancy stage and almost absent post partum. Abnormal taste sensitivity was fairly commonly reported (26%), often described as increased bitter sensitivity and decreased salt sensitivity. These results, suggesting that abnormal smell and/or taste perception is experienced by a large majority of pregnant women, imply that further research is needed to understand to what extent these chemosensory changes may underlie food aversions and craving with implications for food intake during pregnancy.     

Improvement of in vitro fertilisation after treatment with buserelin,an agonist of luteinising hormone releasing hormone

Treatment with buserelin, an agonist of luteinising hormone releasing hormone, and human menopausal gonadotrophin was compared with the conventional treatment of clomiphene citrate and human menopausal gonadotrophin in the outcome of in vitro fertilisation. Seventy seven infertile women had 83 cycles of treatment with buserelin and human menopausal gonadotrophin, and concurrently another 328 infertile women were treated with clomiphene citrate and human menopausal gonadotrophin. Seven (8%) cycles were cancelled owing to inadequate superovulation or ovarian hyperstimulation in the women receiving buserelin and 103 (31%) were cancelled because of poor follicular development in those receiving clomiphene citrate. The mean number of oocytes recovered was significantly higher with buserelin (9·5 (SD 4·5) v 5·5 (2·2)) as was the mean number of embryos obtained (4·3 (2·4) v 2·9 (1·7)). Significantly more women who had an embryo transfer became clinically pregnant after treatment with buserelin (53% (30/57) v 30% (48/159), or 36% v 14% of treatment cycles). Altogether 33% (10) of pregnancies in women treated with buserelin were multiple compared with 23% (11) in those treated conventionally. Of the 17 completed pregnancies in women treated with buserelin, 11 resulted in the birth of live babies (eight singletons, two sets of twins, and one set of triplets) and six failed, five before 12 weeks'' gestation and one at 22 weeks. The 13 continuing pregnancies (32 weeks) were eight singletons, two sets of twins, and three sets of triplets. Of the 48 completed pregnancies in women treated with clomiphene citrate, 35 resulted in the birth of live babies (26 singletons, five sets of twins and four sets of triplets) and 13 failed, eleven before 12 weeks'' gestation and two by 27 weeks.Buserelin increased the chance of pregnancy after in vitro fertilisation compared with conventional treatment, but the risk of multiple pregnancy may be increased.     

Influence of pregnancy on the course of malaria in mice infected with Plasmodium berghei

The course of malarial infection was compared in pregnant mice inoculated with Plasmodium berghei at different stages of gestation. When 12-14 wk old, pregnant BALB/c mice were inoculated with 1 x 10(6) of P. berghei NK65-infected red cells at gestation day 0, 2, 4, 6, 8, 10, 12, 14 or 16, the mice inoculated on gestation days 6-12 expired 6.5 days after inoculation compared to 9.5 days in non-pregnant mice. Parasitemia in these pregnant mice increased rapidly on day 4 after inoculation and anemia also developed earlier on day 5. However, the degree of parasitemia and anemia in the terminal stage of infection in these pregnant mice was milder than that of non-pregnant controls. Blood urea nitrogen increased at the terminal stage although the degree of increase in mice inoculated on gestation days 6-10 was comparatively small. Pregnant malarial mice died earlier with less physiological changes than non-pregnant controls. It was concluded that pregnancy makes the host susceptible to physiological changes caused by malaria.     

Prostaglandin production by the early pregnant guinea-pig uterus in relation to implantation and luteal maintenance, and the effect of oestradiol

The outputs of prostaglandin (PG) F-2 alpha and PGE-2, but not of 6-oxo-PGF-1 alpha, from the guinea-pig uterus were significantly lower on Days 7 and 15 of pregnancy than on the corresponding days of the cycle. Uterine PGF-2 alpha output increased 28-fold between Days 7 and 15 of the cycle but only 4- to 5-fold between these same days of pregnancy. Uterine PGE-2 and 6-oxo-PGF-1 alpha outputs increased 2- to 3-fold between Days 7 and 15 of the cycle and of pregnancy. Endometrial PGF-2 alpha synthesizing capacity was 60-70% lower on Days 7 and 15 of pregnancy than on the corresponding days of the cycle, although it increased 2-fold and 2.5-fold between these days of pregnancy and of the cycle, respectively. Endometrial PGE-2 and 6-oxo-PGF-1 alpha synthesizing capacities showed no significant variation amongst Days 7 and 15 of the cycle and of pregnancy, except that endometrial PGE-2 synthesizing capacity was lower on Day 7 of the cycle. Oestradiol treatment (10 micrograms s.c. daily from Days 10 to 14 of pregnancy) did not affect plasma progesterone concentrations, uterine 6-oxo-PGF-1 alpha output, and endometrial PGF-2 alpha, PGE-2 and 6-oxo-PGF-1 alpha synthesizing capacities in 9/12 guinea-pigs when examined on Day 15. Uterine PGF-2 alpha and PGE-2 outputs increased 3- and 1.5-fold, respectively, in these guinea-pigs, but were still much lower than the outputs from the Day-15 non-pregnant uterus. The pregnancies appeared unaffected in these oestradiol-treated guinea-pigs. In the other 3 oestradiol-treated animals, uterine PGF-2 alpha output was 20- to 30-fold higher than in untreated, pregnant guinea-pigs on Day 15, and 2- to 3-fold higher than in Day-15 non-pregnant guinea-pigs. Uterine PGE-2 and 6-oxo-PGF-1 alpha outputs also tended to be higher in these treated guinea-pigs. In these 3 guinea-pigs, endometrial PGF-2 alpha, PGE-2 and 6-oxo-PGF-1 alpha synthesizing capacities were 4.0-, 3.4- and 2.5-fold higher, respectively, than in untreated, pregnant guinea-pigs on Day 15, and tended to be higher than in Day-15 non-pregnant guinea-pigs. Plasma progesterone concentrations were much lower in these 3 animals than in the other 9 treated with oestradiol, and also much lower than in untreated, pregnant guinea-pigs on Day 15.(ABSTRACT TRUNCATED AT 400 WORDS)     

Increase in urinary thromboxane excretion during pregnancy and labor

Urinary TXB2 excretion was measured during pregnancy and labor using high pressure liquid chromatography and radioimmunoassay. From the first trimester onwards TXB2 levels in urine of pregnant women (n = 60) were significantly (p less than 0.001) higher than in non-pregnant women (n = 12) and they increased, albeit not significantly, with advancing gestation. Labor was associated with a two-fold increase in urinary TXB2 excretion. Levels in established labor were significantly higher than at any other time in pregnancy (p less than 0.001), but the levels in incipient labor showed considerable overlap with these in late pregnancy. Thus urinary TXB2, while not necessarily originating from the pregnant uterus, appears to reflect the uterine activity of labor and may be the expression of a general stimulation of prostanoid production during parturition.     

Effects of early pregnancy on regional adipose tissue metabolism

Adipose tissue metabolism was studied in needle biopsies from femoral and abdominal subcutaneous depots, in 12 healthy young women, during early (9-11 weeks) pregnancy, and 6 weeks after a legal abortion. Both during pregnant and non-pregnant conditions, a higher lipoprotein lipase (LPL) activity was seen in the femoral compared to the abdominal region, but the LPL activity was not influenced by early pregnancy. Rates of fatty acid esterification and acylglyceride synthesis were not different between regions, nor affected by pregnancy. The stimulatory effect of norepinephrine (10(-7) M) on lipolysis was significantly greater in the abdominal than in the femoral region in both the pregnant and non-pregnant condition. This difference was apparently due to higher alpha-adrenergic activity in the femoral region. Pregnancy per se had no effect on lipolytic response to norepinephrine. These findings indicate that lipid accumulation is favoured in the femoral region in young women both during pregnant and non-pregnant conditions.     

Serum concentrations of immunoglobulins and acute phase proteins in Nigerian women with preeclampsia

Preeclampsia is a pregnancy-specific condition that increases maternal and infant mortality and morbidity. It is diagnosed based on a triad of hypertension, significant proteinuria and rapidly increasing edema during gestation. The factors that initiate preeclampsia are unknown and still a subject of intense clinical research. The objective of this study is to provide additional immunological information about preeclampsia. To achieve this, humoral immunochemical parameters such as three classes of immunoglobulin (IgA, IgG and IgM) and three acute phase proteins (alpha 2-macroglobulin, haptoglobin and transferrin) were measured by single radial immunodifussion method in 32 pregnant women with preeclampsia, 36 pregnant women without preeclampsia and 24 non-pregnant women (controls). Total protein in the urine was also determined by spectrophotometric method. In women with preeclampsia, the levels of IgG, IgA, transferrin and alpha 2-macroglobulin were significantly reduced compared with subjects with normal pregnancy, but the level of haptoglobin was significantly raised in preeclampsia compared with women having normal pregnancy. Urinary total protein and IgG were significantly raised in Nigerian women with preeclampsia compared with non-pregnant controls. There were significant negative correlations between serum IgG, IgA and urinary protein. The possible involvement of immunoglobulins and acute phase proteins in preeclampsia is discussed.     

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.     

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.     

Luteolytic action of 15-keto prostaglandin F2alpha in the rhesus monkey.

The naturally-occurring metabolite of prostaglandin F2alpha, 15-keto prostaglandin F2alpha (15-keto PGF2alpha), elicited rapid and sustained declines in serum progesterone concentrations when administered to rhesus monkeys beginning on day 22 of normal menstrual cycles. Evidence for luteolysis of a more convincing nature was obtained in studies where a single dose of 15-keto PGF2alpha was given on day 20 of ovulatory menstrual cycles in which intramuscular injections of hCG were also given on days 18-20; serum progesterone concentrations fell precipitously in monkeys within 24 hours following intramuscular administration of 15-keto PGF2alpha. However, corpus luteum function was impaired in only 4 of 11 early pregnant monkeys when 15-keto PGF2alpha was administered on days 30 and 31 from the last menses, a time when the ovary is essential for the maintenance of pregnancy. Gestation failed in 2 additional monkeys 32 and 60 days after treatment with 15-keto PGF2alpha, but progressed in an apparently normal manner in the remaining 5 animals. Two pregnant monkeys treated with 15-keto PGF2alpha on day 42 from the last menstrual period, a time when the ovary is no longer required for gestation, continued their pregnancies uneventfully. Corpus luteum function was not impaired in 9 control monkeys which received injections of vehicle or hCG at appropriate times during the menstrual cycle or pregnancy.     

Glucocorticoid Metabolism in Hypertensive Disorders of Pregnancy: Analysis of Plasma and Urinary Cortisol and Cortisone

Objectives

The aim of the study was to analyze the plasma and urinary cortisol (F) and cortisone (E) levels in normotensive and hypertensive pregnant women. The parameters known to reflect the function of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) were calculated to verify the changes in glucocorticoid balance over the course of gestational hypertension (GH) and pre-eclampsia (PE).

Materials and Methods

This retrospective case-control study included women in the third trimester of pregnancy, diagnosed with: GH (n = 29), PE (n = 26), or chronic hypertension (CH; n = 22). Normotensive women in their third trimester of pregnancy were also included (controls; n = 43). The plasma and urinary F and E levels were measured with the HPLC-FLD method. The 11β-HSD2 function was estimated by calculating the following ratios: plasma F/E and urinary free F to urinary free E (UFF/UFE). A statistical analysis was performed based on case-control structure.

Results and Discussion

PE was characterized by lower plasma F levels (639.0 nmol/L), UFF/Cr levels (3.80 μg/mmol) and F/E ratio (3.46) compared with that of the controls (811.7 nmol/L, 6.28 μg/mmol and 5.19, respectively) with marked abnormalities observed in the changes of F/E and UFF/UFE ratios with advancing gestation. GH patients showed significant disparities in the urinary steroid profile with lower UFF/UFE ratio (0.330 vs. 0.401) compared with the normotensive controls and abnormal changes in the UFF/UFE throughout pregnancy. The observed tendency towards lower F/E and UFF/UFE ratios in PE and GH patients may reflect more intensive F metabolism over the course of those disorders. In the normal pregnancy group, the plasma F/E and UFF/UFE ratios tended to present inverse correlations with advancing gestation. This trend was much less marked in PE and GH patients, suggesting that the abnormalities in 11β-HSD2 functions progressed with the GA. The birth weights of neonates born from pre-eclamptic pregnancies were lower than those from uncomplicated pregnancies, although only when the babies were born prematurely. Children born at term to normotensive mothers or mothers suffering from PE had comparable birth weights.