Effects of pregnancy on spatial cognition in female Hooded Long-Evans rats

Studies examining the roles of estrogens and progestins on spatial cognition have been highly contradictory. To determine if the hormonal environment of pregnancy affects spatial cognition, pregnant (n = 7) and virgin (n = 7) Hooded Long-Evans rats were tested in a Morris water maze throughout the 3 weeks of pregnancy and the second week postpartum. Latency to platform, path length, swim velocity, and time in quadrant were compared over trial-days. To compare water maze performance with changes in hormone levels, serum concentrations of estradiol and progesterone were measured on the first, third, and fifth days of testing during the third week of pregnancy. Subjects learned to find the platform as indicated by decreased time and distance to platform over each trial-week and increased time spent in the quadrant where the platform had been located the previous week. However, there were no differences between treatment groups on time or distance to platform over trial-days. Swim velocity did not differ between or within groups over the 4 weeks of testing. Although primigravid and virgin females were similar in their abilities to learn the novel location of a submerged platform and return to it over time, pregnant animals demonstrated less perseveration to previously learned information and were quicker to locate the platform when it moved to a new location. Thus, reproductive status did not affect reference memory but enhanced working memory in the Morris water maze.     

Zinc and copper concentrations in serum from Spanish women during pregnancy

A cross-sectional study of serum zinc (Zn) and copper (Cu) levels in 31 healthy pregnant women and 51 healthy, nonpregnant controls living in the Mediterranean area of Granada, Spain, was performed. The subjects were divided into two groups: Group A, consisted of pregnant women in three categories according to the trimester of pregnancy, and Group B consisted of nonpregnant women acting as controls. In pregnant women, serum Zn levels were found from 0.300-1.340 mg/L and serum Cu from 0.936-2.304 mg/L, whereas in the nonpregnant women group, the mean serum levels were 0.947 ±0.265 mg/L for Zn and 1.092 ±0.365 mg/L for Cu. Serum Zn progressively decreased with gestation. Mean Zn levels were 0.829 ±0.253, 0.846 ±0.329, and 0.620 ±0.142 mg/L, corresponding to the first, second, and third trimesters of pregnancy, respectively. Serum Zn concentrations were significantly lower in pregnant women as compared to controls: 0.712 ±0.236 mg/L vs 0.947 ±0.265 mg/L, respectively (p < 0.05). In contrast, Cu levels increased with period of gestation from 1.053 ±0.498 mg/L in the first trimester to 1.616 ±0.304 mg/L in the second and 1.689 ±0.344 mg/L in the third. Serum Cu levels in the second and third trimesters of pregnancy were significantly higher (p < 0.05) than those determined during the first trimester and for nonpregnant controls. Both Zn and Cu during pregnancy did not appear to be dependent on the subject’s age (p > 0.05).     

Trypanosoma lewisi: termination of pregnancy in the infected rat

Trypanosoma lewisi has previously been described as a nonpathogenic parasite of the rat, but these experiments demonstrate that both embryonal and maternal death may occur in the pregnant rat after infection with this parasite.Rats infected early in the first week of pregnancy resorbed their young with little apparent difficulty, and exhibited parasitemia curves typical of nonpregnant infected females of similar age.Rats infected late in the first week of pregnancy experienced greater difficulty resorbing the young, with half of the females dying shortly before parturition. The parasitemia counts were also similar to those of nonpregnant infected rats.The majority of rats infected during the midterm of pregnancy died at the time of parturition, without giving birth to their young. The number of parasites in these animals was abnormally high compared to nonpregnant infected females. Unusually large numbers of dividing trypanosomes were present in the placentae of these animals, many of them containing 8–16 nuclei and kinetoplasts.Animals infected during the last week of pregnancy gave birth to litters of normal size with little apparent difficulty, and had extremely low parasite counts.The hematocrits of all groups of infected animals showed a decrease at the time of peak parasitemia, and the hematocrits of all groups of pregnant rats showed a decrease at the time of birth, except for those infected when day 2 pregnant. These animals completely resorbed their young. The weight losses of rats infected on day 2 and day 6 of pregnancy reflected a termination of pregnancy.     

The effects of oxidative stress in urinary tract infection during pregnancy

The purpose of this study was to determine the effect of urinary tract infection (UTI) on antioxidant systems and lipid peroxidation (LPO) levels during pregnancy. We also investigated if these antioxidant systems and LPO levels differed in each trimester. One hundred forty-three nonpregnant women, as a control group, and 77 pregnant women were included in the study. Urine cultures were performed according to standard techniques. Catalase (CAT), superoxide dismutase (SOD), and LPO levels were measured using a spectrophotometer. UTI was observed in 14 of 77 pregnant women and the isolated microorganisms were Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus. CAT, SOD, and LPO levels were increased in pregnant women compared with nonpregnant women (P<.01). CAT, SOD activities, and LPO levels were increased from the first trimester to the third trimester in pregnancy without UTI. However, CAT and SOD activities were decreased, LPO levels were increased from the first trimester to the third trimester in pregnancy with UTI (P<.01). Pregnancy causes oxidative stress and also UTI during pregnancy may aggravate oxidative stress.     

Detection of pregnancy in a hibernator based on activity data

Pregnancy and parturition are often difficult to detect in wild-living animals, especially in species that give birth to altricial young in burrows or caves. Current methods to detect pregnancy and birth in hibernating animals often entail disturbances that can affect the animals' reproductive success. We developed a new method to confirm pregnancy and parturition in hibernating brown bears (Ursus arctos) using activity data recorded in dual-axis motion sensors mounted on GPS–GSM neck collars on 30 brown bears during 52 hibernation seasons in Sweden. We adjusted recorded activity to the individual basal activity level for each bear. Pregnant females showed characteristic activity patterns during the period of pregnancy, with significantly higher daily activity levels and frequency of active periods during pregnancy than nonpregnant bears. Pregnant females were active on average 2.20 times more often during the pregnancy period than during the postpartum period, compared with 0.97 times for nonpregnant females. A pregnancy index was defined as the average of the proportion of mean daily activity levels and the proportion of activity events during the pregnancy period compared with the postpartum period. It averaged 2.61?±?1.73 (SD) for pregnant females and 0.94?±?0.24 for nonpregnant females. Using this method, we evaluated a group of adult females that had an unverified reproductive status but were classified as not pregnant because no cubs had been observed after den emergence. The results suggested that 35 % of those females had, in fact, been pregnant.     

Serum thyroglobulin concentration in normal pregnancy

We measured the levels of serum thyroglobulin (Tg) in 52 pregnant females at various stages and compared them with those of 15 age-matched nonpregnant females. Serum Tg was measured by a solid-phase immunoradiometric assay. In pregnant females, mean serum Tg levels at the first, second, early third, and late third trimesters were 8.4 (range; 1.3-18.0), 9.2 (1.7-25.6), 10.1 (1.8-22.8), and 12.1 ng/ml (5.3-25.2), respectively. The statistical comparison was made after logarithmic transformation of the data. The mean value only at the late third trimester was significantly higher than that of controls (mean; 6.0 ng/ml, range; 1.5-23.6), but each value was within the normal range. Although serum Tg levels have been reported to be high at the end of pregnancy, our results indicate that the Tg levels in females could be clinically interpreted without regard to the coexistence of pregnancy.     

Hormonal evidence for induced ovulation in Monodelphis domestica.

Breeding activity in the South American grey opossum, Monodelphis domestica, is stimulated by the presence of males. This study presents the first analysis of changes in concentrations of plasma progesterone during pregnant and nonpregnant cycles. In Expt 1, females were paired with either intact or vasectomized males to stimulate a reproductive cycle, or were isolated from males. Within 4-8 days of pairing, females showed marked changes in the size of the urogenital opening (vulva), which were paralleled by similar changes in body weight (11.4 +/- 2%; mean +/- SEM; n = 13). There was a second increase and decrease in body weight (21.7 +/- 3.3%; n = 13) in pregnant and nonpregnant cycles during the luteal phase of the cycle. Changes in concentrations of plasma progesterone, determined from samples collected three times a week, were similar in pregnant and nonpregnant cycles. Plasma progesterone concentration, which was increased for 15-18 days, showed two distinct peaks. The first peak, 3-4.5 ng ml-1, occurred immediately after the decrease in vulval swelling, and the second peak (1-2 ng ml-1) occurred 8-12 days later. Concentrations of plasma progesterone were low before parturition occurred. Females isolated from males for 35 days showed no changes in body weight or vulval swelling and concentrations of plasma progesterone remained undetectable. In Expt 2, concentrations of luteinizing hormone (LH) in plasma were determined twice a day for the first few days after pairing. In three of five females an LH peak was detected coincident with the maximal swelling of the vulva.     

Selenium and malondialdehyde content and glutathione peroxidase activity in maternal and umbilical cord blood and amniotic fluid

Placenta tissue may be a major source of lipid peroxidation products in pregnancy. It was proven that placental peroxidation activity increases with gestation. Selenium (Se), as an essential constituent of glutathione peroxidase (GSH-Px), takes part in the reduction of hydrogen peroxides and lipid peroxides. Malondialdehyde (MDA) is a major breakdown product split off from lipid peroxides. In this study, Se and MDA content and GSH-Px activity were measured in blood and plasma taken from 20 apparently healthy nonpregnant women between 19 and 38 yr of age and from 115 unselected pregnant women between 17 and 45 yr of age (35 in the first trimester, 22 in the second trimester, 38 in the third trimester, and 20 within 2 d of delivery). Samples of umbilical cord blood and amniotic fluid were taken from women in the second and third trimesters and at delivery. The Se content was measured by atomic absorption spectrometry (AAS), plasma MDA concentration by thiobarbituric acid reaction, and Se-dependent GSH-Px spectrometrically. Blood and plasma Se contents of nonpregnant women were below those considered adequate, indicating low selenium intake. In comparison to nonpregnant women, pregnant women had significantly decreased whole-blood and plasma Se levels in the second and third trimesters and at delivery. The significant drop of whole-blood SeGSH-Px activity was observed in the first trimester of pregnancy and its lower activity was maintained until delivery. A significant drop in plasma SeGSH-Px activity occurred in the second trimester and attained the minimal level at delivery. The Se level and SeGSH-Px activity in maternal and umbilical cord blood were at similar levels. Amniotic-fluid SeGSH-Px activity was nondetectable or exceptionally low and its Se content remained unchanged during pregnancy. Plasma levels of MDA were significantly decreased in the second and third trimesters and at delivery. The fetal blood plasma at birth had a lower MDA level compared to the levels of MDA of their mothers at delivery. A low, but significant inverse correlation existed between blood SeGSH-Px activity and plasma MDA content and between plasma Se and plasma MDA contents during pregnancy. A significant decrease of Se and SeGSH-Px activities (antioxidant enzyme) in both blood and plasma suggests a possible drop in total antioxidant status during pregnancy. Elevated MDA plasma levels might be the result of increased lipid peroxidation in placental tissue during pregnancy.     

Attenuated hypotensive response to proadrenomedullin N-terminal 20 peptide in pregnant rats: modulation by steroid hormones

The hypotensive effect of proadrenomedullin N-terminal 20 peptide (PAMP) was examined in conscious pregnant (8, 14, and 20 days of pregnancy) and nonpregnant rats. Intravenous administration of PAMP (3–60 nmol/kg) produced a dose-dependent depressor response in both pregnant and nonpregnant rats. However, the maximum decrease in blood pressure was significantly attenuated in pregnant rats in mid- and late-gestation (14 and 20 days), but not in early gestation (8 days), than in nonpregnant rats. In ovariectomized rats, the depressor responses in 17β-estradiol (E2)-treated, progesterone (P)-treated, and E2+P-treated rats were significantly attenuated compared with the control rats. We also demonstrated that treatment of sex hormones reduces the depressor response to PAMP in 8-day pregnant rats. In addition, we showed that treatment of sex hormone receptor antagonists partially prevents the attenuation of the depressor response to PAMP in 20 day pregnant rats. These findings suggested that the hypotensive response to PAMP was more attenuated in pregnant rats in mid- and late-gestation than in nonpregnant rats, and that the changes in depressor response that occur at term in pregnant rats may be mediated by sex hormones. PAMP may play some important role in cardiovascular regulation during pregnancy.     

Pregnancy rates relative to recipient plasma progesterone levels on the day of nonsurgical transfer of frozen/thawed bovine embryos

A total of 71 synchronized dairy heifers (Holstein Friesian x German Black Pied) were used as recipients of seven-day old frozen/thawed bovine embryos. Plasma progesterone concentrations and corpus luteum quality on the day of nonsurgical transfer (= day 7) were determined and related to pregnancy rates or estrus intervals in nonpregnant recipients. A total of 32 recipients (45.1 %) maintained pregnancy; 39 recipients (54.9 %) did not. No significant differences could be detected between progesterone levels in recipients that remained pregnant (3.14 +/- 0.24 ng/ml; x +/- SEM ) and those that did not maintain pregnancy (3.23 +/- 0.28 ng/ml). Optimal progesterone levels were between 2 and 5 ng/ml coinciding with a pregnancy rate of 51.1 % (24 47 ). Pregnancy rates apparently were decreased when progesterone levels were below 2 ng/ml (35.3 %; 6 17 ) or above 5 ng/ml (28.6 %; 2 7 ). Hence, optimal progesterone levels were identical to those for freshly collected embryos reported previously by Remsen et al. (1). Bovine corpus luteum quality graded by rectal palpation was related to some extent to progesterone levels but not to pregnancy rates. Out of 39 nonpregnant recipients seven animals (17.9 %) with a mean plasma progesterone level of 3.76 +/- 0.72 ng/ml showed an extended estrus interval of more than 55 days, probably indicating early embryonic mortality. Progesterone levels did not significantly differ between nonpregnant recipients with estrus intervals of various length. Plasma progesterone levels at the time of transfer are of limited diagnostic value for screening recipients prior to transfer of frozen/thawed embryos.     

Dissociation of copulation from ovulation in pregnant rabbits

Experiments were designed to determine why copulation in the pregnant rabbit does not terminate pregnancy while treatment with ovulatory doses of luteinizing hormone (LH) human chorionic gonadotropin (hCG) or luteinizing hormone-releasing hormone (LHRH) is known to do so. Pregnant rabbits (Day 8) were mated or were injected with hCG (25 IU/doe) or LHRH (1, 10 micrograms/kg). Serial blood samples were collected over the next 72 h and analyzed for content of LH, follicle-stimulating hormone (FSH) and progesterone. At sacrifice, uteri and ovaries from these animals were examined for viability of the embryos and for signs of recent ovulation. Injection of hCG or LHRH into pregnant animals led to ovulation and to patterns of LH, FSH and progesterone secretion like those which precede ovulation in estrous rabbits. However, mating the pregnant does did not lead to ovulation or to any changes in the circulating hormones. To investigate whether the elevated levels of progesterone during pregnancy were responsible for the dissociation of coitus from ovulation, nonpregnant rabbits were injected with progesterone (2 mg/kg) and then mated or injected with hCG or LHRH. In virtually every respect, the numbers of ovulations and the patterns of hormone secretion in the progesterone-treated, nonpregnant rabbits mimicked those observed in the 8-day pregnant animals; injection of hCG or LHRH caused ovulation and hormonal surges while hCG caused ovulation only. Mating did not lead to ovulation or any change in blood levels of LH, FSH or progesterone. Taken together, the results show that the elevated circulating levels of progesterone, characteristic of pregnancy, are probably responsible for the dissociation of copulation from gonadotropin release in pregnant rabbits.     

Gestational profile of leptin messenger ribonucleic acid (mRNA) content in the placenta and adipose tissue in the rat, and regulation of the mRNA levels of the leptin receptor subtypes in the hypothalamus during pregnancy and lactation

Serum leptin levels were significantly increased during rat gestation. Our data showed that leptin mRNA levels in both the adipose tissue and placenta were higher as pregnancy progressed, suggesting a role for both tissues in the hyperproduction of leptin. This paradoxical increase in leptin concentration during gestation suggests that a physiological state of leptin resistance may exist at the hypothalamic level that may explain the hyperphagia observed in pregnant rats. In order to study this issue further, levels of the mRNA encoding the different leptin receptor isoforms were determined in the hypothalamus of pregnant and nonpregnant rats. We found a specific reduction of the mRNA levels encoding the leptin receptor isoform Ob-Rb in the hypothalamus of pregnant rats compared to nonpregnant animals, suggesting that during pregnancy the hypothalamus shows a physiological resistance to the high levels of leptin due, at least in part, to a decrease in the expression of the long, biologically active form of the leptin receptor (Ob-Rb). During lactation, serum leptin levels returned to values observed in nonpregnant rats. In the hypothalami of these animals, Ob-Rb mRNA content was similar to that observed in nonpregnant rats, but we found an increased expression of some of the short forms of the leptin receptor (Ob-Re and Ob-Rf). This could contribute to induction of the hyperphagia present during lactation. These data provide new insights into the adaptive mechanisms that take place during pregnancy and lactation in order to meet increased metabolic requirements.     

Effect of antiprogestin ZK 98.734 on the ovarian cycle, early pregnancy, and on its binding to progesterone receptors in the myometrium of marmoset Callithrix jacchus

The antiprogestin ZK 98.734 (11 beta-(4-dimethylaminophenyl-17 beta-hydroxy-17 alpha-(3-hydroxy-prop-1(Z)-enyl-4,9(10)-estradien-3-one) was administered i.m. (5 mg/day) for three consecutive days to two groups of common marmosets. In one group (nonpregnant, n = 6), it was injected during the luteal phase, and to the second group (pregnant, n = 7), it was injected during early pregnancy, on Days 24-26 of the mid-cycle estradiol peak. Administration of ZK 98.734 during the luteal phase caused a sharp drop in plasma progesterone levels. The luteal phase was shortened whether the drug was administered during the early or the late luteal phase. Similarly, administration of ZK 98.734 during early pregnancy caused a significant drop in progesterone levels, and pregnancy was terminated in all of the animals. The post-treatment cycles in both groups of animals were ovulatory and of normal duration. 3H-ZK 98.734 showed specific binding to myometrial cytosol fraction. ZK 98.734 also displaced the binding of 3H-progesterone to progesterone receptors. However, progesterone had higher binding affinity than did ZK 98.734. The antifertility action of ZK 98.734 could be a result either of its luteolytic action or of its blocking the progesterone receptors in the target tissue. This study, therefore, indicates that in the common marmoset ZK 98.734 is a progesterone antagonist with a potential to terminate early pregnancy.     

Acute administration of estrogen and progesterone impairs the acquisition of the spatial morris water maze in ovariectomized rats

Although several markers of synaptic efficacy are enhanced during proestrus, spatial water maze performance is impaired. Because levels of both estrogen and progesterone are elevated in proestrus, the nature of their individual and combined effects on spatial learning was examined. Long-Evans hooded rats were ovariectomized postpubertally and pretrained on a water maze with a visible platform (nonspatial). Following pretraining, rats were administered estrogen (5 microg sc) or oil 48 and 24 h prior to testing and progesterone (500 microg sc) or oil 4 h prior to testing. Rats were tested on a water maze in a different room with a submerged platform (spatial) for 16 trials with random start location in a single testing day. Latency and path length to the target platform were significantly greater in estrogen plus progesterone-treated animals than in controls. Neither estrogen nor progesterone alone significantly impaired performance relative to controls on either measure. Swim speed was not significantly affected by any of the hormone treatments. Performance on a nonspatial cue task was not significantly altered by ovarian steroids. Thus, the combination of estrogen and progesterone produces deficits in the acquisition of the Morris water maze that may be specific to spatial reference memory. These deficits could be due to hormonal influences on extrahippocampal structures or to detrimental effects on behavior resulting from the increased synaptic activity intrinsic to the hippocampus proper.     

Concentrations of insulin-like growth factor-I, estradiol and progesterone in follicular fluid of ovarian follicles during early pregnancy in cattle

To determine if the presence of the developing conceptus is associated with changes in intrafollicular concentrations of insulin-like growth factor-I (IGF-I), estradiol (E2) and/or progesterone during early pregnancy in cattle, either pregnant (n=16) or nonpregnant (n=15) cows were slaughtered on Day 10, 15 or 18 postestrus. Ovaries and follicular fluid were collected. Follicles were grouped by diameter: 1.0 to 3.9 mm (small; n=63), 4.0 to 7.9 mm (medium; n=128), and >/= 8.0 mm (large; n=38). The average diameter of large follicles was greater (P<0.05) in pregnant than in nonpregnant cows on Day 10, but on Day 18 it was greater (P<0.05) in nonpregnant than in pregnant cows (11.3 vs 9.7 mm). Status (pregnant vs nonpregnant) did not affect (P>0.10) follicular fluid progesterone nor IGF-I concentrations. In contrast, the status and days postestrus affected (P<0.05) follicular fluid E2 concentrations. Follicular fluid E2 levels in the three follicle size-categories on Day 10 did not differ (P>0.10) between pregnant and nonpregnant cows. However, on Days 15 and 18 postestrus, follicular fluid E2 concentrations in pregnant cows was lower (P<0.05) in large follicles than in nonpregnant cows. We conclude that the presence of a developing conceptus early in pregnancy may alter follicular growth and inhibit follicular E2 production in cattle. These effects appear to be mediated by factors other than IGF-I.     

Higher incidence of spontaneous sister-chromatid exchanges (SCEs) and X-ray-induced chromosome aberrations in peripheral blood lymphocytes during pregnancy

In vitro cultures of peripheral blood lymphocytes from human and muntjac (barking deer) females who were at an advanced stage of pregnancy (32-37 weeks pregnant women and 20-24 weeks pregnant muntjacs) showed an enhanced frequency of SCEs and X-ray-induced chromosome aberrations when compared with those of nonpregnant females. Lymphocyte cultures of nonpregnant females to which sex hormones progesterone, oestrogen and human chorionic gonadotropin (HCG) were added together exogenously also showed higher frequency of SCEs. The plausible reason(s) for such high incidence of SCEs during pregnancy is discussed.     

Effects of oral aluminum on essential trace elements metabolism during pregnancy

The present study was conducted to assess in rats the effects of oral aluminum (Al) exposure on calcium (Ca), magnesium (Mg), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) accumulation and urinary excretion. Three groups of plug-positive Sprague-Dawley (SD) rats were given by gavage 0, 200, and 400 mg/kg/d of Al(OH)₃ on gestational days 1–20. Three groups of nonpregnant female SD rats of the same age received Al(OH)₃ by gavage at the same doses for 20 consecutive days. At the end of the treatment period, 24-h urine samples were collected for analysis of Al and essential elements. Subsequently, all animals were sacrificed and samples of liver, bone, spleen, kidneys, and brain were removed for metal analyses. With some exceptions, the urinary amounts of Al, Mn, and Cu excreted by pregnant animals as well as the urinary levels of Al excreted by nonpregnant rats were higher in the Al-treated groups than in the respective control groups. Although higher Al levels were found in the liver of pregnant rats, the concentrations of Al in the brain of these animals were lower than those found in the same tissues of nonpregnant rats. With regard to the essential elements, tissue accumulation was most affected in pregnant than in nonpregnant animals. In pregnant rats, the hepatic and renal concentrations of Ca, Mg, Mn, Cu, Zn, and Fe, as well as the levels of Ca in bone, and the concentrations of Cu in brain were significantly higher in the Al-exposed groups than in the control group. According to the current results, oral Al exposure during pregnancy can produce significant changes in the tissue distribution of a number of essential elements.     

The effects of progesterone on follicular growth in the rabbit ovary

Studies were undertaken to measure the growth of follicles in the rabbit ovary during periods of elevated blood levels of progesterone. The progestin was increased in the blood by pregnancy or by implantation of progesterone pellets, which raised blood progesterone to near the levels measured during pregnancy. After 1, 2, 3, or 4 weeks of pregnancy or progesterone-pellet treatment, follicles of 1.0 mm external diameter or greater were dissected out of the ovaries and their external diameters were measured; then, each follicle was extracted for measurement of estradiol content. Blood levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in these animals as well. Follicles up to 2.5 mm in diameter were found in the ovaries of nonpregnant and untreated animals while 1.8 mm was the maximal size found during pregnancy or progesterone-pellet treatment. Furthermore, both in pregnant and in progesterone-treated rabbits, the follicular estradiol content and concentration were significantly suppressed compared to follicles from untreated rabbits. The progesterone pellets had no major effect on the levels of LH and FSH in the blood; the concentration of these gonadotropins in the progesterone-treated rabbits was virtually identical to levels previously measured in the blood of pregnant animals. The results of these studies indicate that progesterone exerts an inhibitory action on follicular development and steroidogenic function in the rabbit ovary. The progesterone action appears to be exerted directly on the ovary and is not indirect, by way of an inhibition of gonadotropin secretion.     

Regulation of maternal ACTH in ovine pregnancy: does progesterone play a role?

Pregnancy is characterized by increased plasma adrenocorticotropic hormone (ACTH) and cortisol. Studies suggest that progesterone acts as an antagonist at mineralocorticoid receptors. Therefore, we tested the hypothesis that chronic progesterone, produced by treatment of nonpregnant ewes or during pregnancy, will result in increased plasma ACTH relative to the plasma cortisol concentrations. We studied three groups of ewes: ovariectomized nonpregnant, nonpregnant treated with progesterone, and pregnant ewes. In two series of studies, ewes were adrenalectomized and replaced with 0.35 mg x kg(-1) x day(-1) or 0.5 mg x kg(-1) x day(-1) cortisol. In both studies, aldosterone was infused at 3 microg x kg(-1) x day(-1). In the first study, additional infusions of cortisol over 24 h were used to increase daily replacement doses to 0.5, 1, or 1.5 mg x kg(-1) x day(-1), and intact pregnant and nonpregnant ewes were studied with infusions of cortisol at 0, 0.5, and 1 mg x kg(-1) x day(-1). In adrenalectomized ewes chronically replaced to 0.35 mg x kg(-1) x day(-1) cortisol, plasma ACTH concentrations were decreased significantly in the nonpregnant progesterone-treated ewes compared with the ovariectomized nonpregnant ewes. With 0.5 mg x kg(-1) x day(-1) cortisol, plasma ACTH levels were greater in pregnant ewes than in nonpregnant ewes with or without progesterone. Overall plasma ACTH levels at 0.35 mg x kg(-1) x day(-1) were significantly related to the plasma protein concentration, suggesting that the ACTH levels in the hypocorticoid ewes are most closely related to plasma volume. Across all steroid doses, ACTH was positively related to plasma proteins and progesterone, and negatively related to cortisol. We conclude that increased progesterone does not alter the feedback relation of cortisol to ACTH, but may modulate ACTH indirectly through plasma volume.     

Vascular hyperresponsiveness to adrenomedullin during pregnancy is associated with increased generation of cyclic nucleotides in rat mesenteric artery

Cardiovascular adaptation is a hallmark of pregnancy. Here we report on vascular hyperresponsiveness to an endogenous vasodilator, adrenomedullin (ADM), during pregnancy. Intravenous administration of ADM dose dependently decreased the mean arterial pressure, and the decrease was significantly greater in pregnant compared with nonpregnant rats without affecting the heart rate. In endothelium-intact mesenteric artery precontracted by ED70 concentration of norepinephrine, the potency and efficacy of ADM in causing the vasodilation of mesenteric arterial rings from pregnant rats are significantly higher compared with nonpregnant females at diestrus. The magnitude of inhibition of concentration-dependent response to ADM by the inhibition of either soluble guanylate cyclase or adenylate cyclase was greater in pregnant rats. Moreover, ADM-induced cyclic nucleotide generation, both cGMP and cAMP, in the mesenteric artery was elevated during pregnancy and was sensitive to the receptor antagonist, ADM22-52. These findings suggest that during pregnancy the vasodilatory effects of ADM are greater and are associated with increased generation of cyclic nucleotides in resistance vessels, and these changes may be part of the cardiovascular adaptations that occur during pregnancy.