MRI: use of the inversion recovery pulse sequence.
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Brain Diseases↗
Biomedical subjects
I R Young
Publications and source records attributed to I R Young.
Fetal and maternal endocrine changes approaching parturition in the goat: lack of evidence for prostaglandins E2 and F2alpha as signals for luteolysis.
We investigated the temporal relationship of fetal cortisol secretion to circulating concentrations of fetal ACTH1-39 and its high-molecular weight precursors in goats. We also measured the concentrations of progesterone, estradiol-17beta estrone sulfate, prostaglandin (PG) E, PGF2alpha, and PGF2alpha metabolite (PGFM) in maternal arterial plasma over the last month of gestation. Prostaglandin concentrations were also measured in utero-ovarian venous plasma. There was a positive association between ACTH1-39 in fetal plasma and the prepartum surge in fetal cortisol that commenced 8 days before labor. The fetal cortisol surge was followed by a simultaneous decrease in maternal progesterone and an increase in plasma estrogens commencing 3-4 days before labor. No change in basal prostaglandin concentration occurred before this time. There was a positive veno-arterial difference of PGE and PGF2alpha across the uterine vascular bed, confirming the uteroplacental unit as a major source of these eicosanoids in the plasma of the pregnant doe. We conclude that the fetal signal for parturition precedes luteolysis by some 5 days and find no evidence of changes in the basal concentrations of PGE and PGF2alpha in maternal plasma at the time of luteolysis.
Adrenocorticotropic Hormone↗
Source of inhibin in ovine fetal plasma and amniotic fluid during late gestation: half-life of fetal inhibin.
Immunoactive inhibin (ir-inhibin) concentrations were determined in chronically catheterized sheep between 120 and 145 days gestation. Maternal plasma ir-inhibin concentrations remained basal (0.19 +/- 0.05 ng/ml) throughout the period of study. Immunoactive inhibin concentrations in male and female fetal plasma were elevated above those observed in maternal plasma, with the concentrations in plasma of male fetuses (7.38 +/- 0.04 ng/ml) being significantly greater (p < 0.001) than those in female fetuses (1.07 +/- 0.14 ng/ml). The concentrations of ir-inhibin in amniotic fluid of ewes bearing male fetuses (10.93 +/- 1.55 ng/ml) were significantly greater than in ewes bearing female fetuses (2.81 +/- 0.32 ng/ml; p < 0.05) but not significantly different from the concentrations in male fetal plasma. Immunoactive inhibin concentrations decreased following surgery in gonadectomized fetuses, to 3.25 +/- 0.99 ng/ml within 6 h, and remained at a mean value of 0.75 +/- 0.38 ng/ml from 24 h after gonadectomy. The half-life of circulating inhibin in fetal plasma, estimated from the decay curve during the first 6 h after surgery, was 3.94 +/- 0.88 h. There was a significant (p < 0.05) decrease in the concentration of ir-inhibin in amniotic fluid after gonadectomy; however, this decrease occurred gradually over 7 days, and ir-inhibin concentrations did not fall to those concentrations observed in fetal circulation at any time after gonadectomy. It is concluded that the major source of circulating ir-inhibin in male fetal plasma, but not in amniotic fluid, is the gonads.
Amniotic Fluid↗
Photoperiodic history and hypothalamic control of prolactin secretion before birth.
We investigated whether the fetal lamb can construct a photoperiodic history in utero. We measured the fetal PRL response to a 12-h photoperiod in intact fetal sheep and in fetal sheep after hypothalamo-pituitary disconnection (HPD), following exposure of the ewe to either a long (16 h L) or short (8 h L) photoperiod for 50 days in early pregnancy. Ewes were maintained on either a long light (LL, n = 20) or a short light (SL, n = 19) regimen from 57 days gestation until fetal HPD (pre-LL, n = 7; pre-SL, n = 7) or sham surgery (pre-LL, n = 13; pre-SL, n = 12) was performed at 99-113 days gestation. All ewes were housed in a 12-h photoperiod from surgery until 140 days gestation. In HPD fetal sheep previously exposed to SL, fetal PRL concentrations were significantly higher (P < 0.05) after 20 days in the 12-h L regimen than previously (0-5 days, 3.2 +/- 0.6 ng/ml; 21-25 days, 5.6 +/- 1.4 ng/ml). In the HPD fetal sheep previously exposed to LL, however, fetal PRL concentrations significantly decreased (P < 0.05) after 5 days exposure to the 12-h L regimen (6.7 +/- 2.9 ng/ml) and remained low throughout the remaining study period (31-35 days, 1.7 +/- 0.5 ng/ml). In contrast, in the sham group there was no effect of photoperiodic history on the gestational age profile of fetal PRL, and PRL concentrations increased significantly (F = 22.4, P < 0.001) in fetal sheep previously exposed to either SL or LL. Fetal PRL concentrations were significantly higher (P < 0.05) after 121 days gestation in the 12-h L regimen in all sham fetal sheep (<110 days, pre-SL 6.4 +/- 0.3 ng/ml, pre-LL 12.0 +/- 3.3 ng/ml; 121-125 days, pre-SL 20.0 +/- 3.9 ng/ml, pre-LL 25.9 +/- 4.4 ng/ml). TRH (50 microg) was administered i.v. to all fetal sheep at 130-134 days gestation. There was a significant fetal PRL response to TRH in both the HPD (F = 20.9, P < 0.001) and sham (F = 31.3, P < 0.001) groups. There was no difference, however, in the PRL response to TRH in fetal sheep previously exposed to SL or LL in either the HPD or sham groups. The maximum percentage changes in PRL occurred at +10 min after TRH administration in the HPD (pre-SL, 421 +/- 75%; pre-LL, 555 +/- 76%) and sham groups (pre-SL, 394 +/- 68%; pre-LL, 369 +/- 59%). In summary, therefore, we have demonstrated that there is an effect of photoperiodic history on the PRL response to an intermediate photoperiod in utero in HPD fetal sheep. It appears, however, that the effect of photoperiodic history on PRL secretion in intact fetal sheep is either masked or suppressed by the stimulatory effect of factors associated with an increase in gestational age acting at the fetal hypothalamus.
Animals↗
Plasma catecholamine and met-enkephalin-Arg6-Phe7 responses to hypoxaemia after adrenalectomy in the fetal sheep.
We have investigated whether removal of the fetal adrenal glands alters the effect of acute hypoxaemia on the circulating concentrations of noradrenaline, adrenaline, Met-Enkephalin and Met-Enkephalin-Arg6-Phe7 (MERF) in the late gestation sheep fetus. Ewes of 6 adrenalectomized and 9 intact fetuses were subjected to a 30 min period of hypoxaemia and a 30 min period of normoxaemia between 135 and 141 days gestation. Removal of the fetal adrenals abolished the fetal adrenaline response and significantly reduced the fetal noradrenaline response to hypoxaemia. There was no significant increase in circulating Met-Enkephalin during either hypoxaemia or normoxaemia in either the intact and adrenalectomized groups. During basal conditions, plasma concentrations of MERF were significantly greater in the adrenalectomized group (1.64 +/- 0.07 ng/ml) than in the intact fetal sheep (1.04 +/- 0.05 ng/ml). There were significantly greater changes (p < 0.05) in plasma MERF concentrations during hypoxaemia than during normoxaemia in both the intact and adrenalectomized groups. Plasma concentrations of MERF were inversely correlated with arterial PO2 (r = -0.44, p < 0.01) in the adrenalectomized but not the intact group of fetal sheep during hypoxaemia. We have demonstrated therefore that the fetal adrenal is the major source of circulating catecholamines, but not Met-Enkephalin or MERF during hypoxaemia in late gestation. The increase in circulating MERF concentrations after adrenalectomy may reflect compensatory changes in the synthesis and/or secretion of MERF in developing sympathetic neurones.
Adrenalectomy↗
Growth and differentiation of fast and slow muscles in fetal sheep, and the effects of hypophysectomy.
1. Isometric contractile characteristics of fast-twitch (flexor digitorum longus, FDL; medial gastrocnemius, MG) and slow-twitch (soleus) muscles were determined in pentobarbitone-anaesthetized fetal sheep between 90 and 140 days gestation. Five fetuses were hypophysectomized (HPX) at 90-95 days gestation and then studied at 138-140 days. 2. At 90-95 days gestation the time to peak of single twitch contractions for the soleus, MG and FDL were not significantly different from each other; the mean value (+/-S.E.M.) for all the muscles at this age was 77.6 +/- 9.0 ms. At 120-125 days gestation the MG and FDL contracted significantly faster (44.0 +/- 0.9 and 40.8 +/- 1.8 ms, respectively) than at 90-95 days, and did not change significantly thereafter. In contrast, the soleus muscle contracted more slowly (111.9 +/- 6.6 ms) at 138-140 days than at 90-95 days and 120-125 days gestation. 3. Soleus muscle consisted of type I fibres at all gestational ages. There was no significant change with gestational age in the relative numbers of type I and II fibres in the MG and FDL, but in the diaphragm the number of type I fibres increased and the number of type II fibres decreased between 125 and 138 days gestation. 4. HPX abolished the normal increase of soleus weight relative to body weight between 125 and 138 days but did not alter the change of twitch contraction time with age. HPX significantly prolonged twitch time to peak and time to half-relaxation of MG and time to half-relaxation of FDL at 138 days. 5. The maximum rate of rise of the isometric tetanic contraction was unchanged by HPX in all three hindlimb muscles, but fatigue of MG and FDL was increased. 6. The relative proportions of different fibre types in the hindlimb muscles and the diaphragm were unchanged by HPX, but there was a significant decrease in mean areas of type I and II fibres in the FDL and MG of the HPX fetuses.
Animals↗
The role of the pituitary-thyroid axis in the developmental regulation of enkephalin-containing peptides in the superior cervical ganglia and adrenal of the fetal sheep.
We have postulated that sympathetic neurones may be one source of circulating enkephalins in the fetus. Therefore, we have investigated the effects of increasing gestational age on the content of the enkephalin-containing peptides in the superior cervical ganglia (SCG) of the fetal sheep during late gestation. We have also investigated the role of the pituitary-thyroid axis in the coordinate regulation of enkephalin-containing peptides within the fetal sympathoadrenal system. We found an increase (P < 0.05) in the content of Free Met-O-Enkephalin between 85 and 105 days (d) (0.46 +/- 0.12 nmoles/SCG) and 116 and 125 d (0.93 +/- 0.12 nmoles/SCG), and the SCG content of Free Met-O-Enkephalin remained elevated throughout the remainder of gestation. The fetal SCG content of Total Met-O-Enkephalin also increased significantly between 85 and 105 d (2.8 +/- 0.5 nmoles/SCG) and 116 and 125 d (7.1 +/- 1.2 nmoles/SCG). There was, therefore, no change in the ratio of Total:Free Met-O-Enkephalin content of the SCG between 85 and 145 d. There were no significant effects of fetal hypophysectomy with or without thyroxine (T4) replacement on the content of Free Met-O-Enkephalin (intact, 1.11 +/- 0.18 nmoles; hypophysectomy (HX) + Sal, 1.41 +/- 0.25 nmoles; HX + T4, 1.08 +/- 0.27 nmoles) or Total Met-O-Enkephalin (intact, 3.03 +/- 0.90 nmoles; HX + Sal, 4.03 +/- 0.22 nmoles; HX + T4, 3.53 +/- 0.88 nmoles) in the fetal SCG. The adrenal contents of Free and Total Met-O-Enkephalin were, however, significantly reduced after fetal hypophysectomy and these effects were not altered by replacement with T4 after fetal hypophysectomy. In summary, we have demonstrated for the first time that enkephalin-containing peptides are present in the SCG of the fetal sheep and that the SCG enkephalin content increases between 85 and 125 days gestation. We have found no evidence that there is a change in the post-translational processing of the enkephalin precursor to Free Met-Enkephalin within the SCG during the second half of gestation. In contrast to the fetal SCG, maintenance of adrenal enkephalin content in late gestation is dependent on the presence of an intact fetal pituitary, but is independent of the circulating concentrations of thyroxine.
Adrenal Glands↗
Thyroxine replacement after hypophysectomy alters the pattern of enkephalin localisation in the adrenal medulla of the fetal sheep.
It has been suggested that a pituitary-derived or -dependent factor may suppress enkephalin peptide synthesis in the central noradrenaline- containing cells of the sheep adrenal medulla in late gestation. We have investigated the effect of thyroxine (T4) replacement after fetal hypophysectomy on the localisation of enkephalin peptides within the peripheral adrenaline- and central noradrenaline-containing regions of the adrenal medulla of the fetal sheep. Fetal hypophysectomy (HX) was performed in 12 fetal sheep at 105-108 days gestation (term = 145 +/- 3 days gestation). T4 (40 micrograms/kg/24h) (HX + T4) or saline (HX + Sal) were infused between 110 and 140 days gestation. Adrenal glands were collected from the HX + T4, HX + Sal groups and from a group of intact fetal sheep (n = 4) for immunohistochemistry using anti- met-enkephalin and an avidin-biotin staining system. In adrenals from intact fetal sheep, there was intense positive staining for met-enkephalin in the peripheral adrenaline-containing region and sparse staining for enkephalins in the central noradrenaline-containing region. In contrast, in the HX + Sal group, enkephalin staining was uniformly present throughout the peripheral and central regions of the adrenal medulla. In the HX + T4 group, however, the staining density of met-enkephalin was higher within the adrenaline cells of the peripheral rim of the medulla than in the central medullary region. We have demonstrated that T4 replacement after fetal hypophysectomy restores the normal ontogenetic pattern of localisation of enkephalin peptides within the fetal adrenal. We postulate that T4 acts either indirectly via neural mechanisms or directly at the noradrenaline-containing cells to mediate the suppression of enkephalin staining within the central noradrenaline-containing region of the adrenal medulla of the fetal sheep in late gestation.
Adrenal Medulla↗
The peptide ACTH(1-39), adrenal growth and steroidogenesis in the sheep fetus after disconnection of the hypothalamus and pituitary.
1. We have investigated the role of the fetal hypothalamo-pituitary axis in the control of adrenocortical growth and steroidogenesis in the sheep fetus during late gestation. Plasma concentrations of ACTH(1-39) increased between 120-125 and 136-142 days (P < 0.05), but did not change after surgical disconnection of the fetal hypothalamus and pituitary (HPD) at 106-120 days gestation. There was no effect of either gestational age or HPD on the circulating concentrations of the ACTH-containing precursors pro-opiomelanocortin (POMC) and pro-ACTH (the 22 kDa N-terminal portion of POMC). 2. In the fetal sheep adrenal, the relative abundance of the mRNAs of the steroidogenic enzymes CYPIIA1 and CYP21A1 increased between 130-135 and 136-140 days gestation (P < 0.05) and remained high after 141 days, whereas that of CYP17 mRNA increased after 141 days gestation (P < 0.05). The abundance of adrenal 3 beta-HSD mRNA did not change between 130 and 145 days. 3. Hypothalamo-pituitary disconnection significantly reduced the abundance of of CYPIIA1 mRNA, 3 beta-HSD mRNA and CYP17 mRNA by 3.4, 3.1 and 3.7 times, respectively, at 140-142 days gestation (P < 0.05). 4. In the intact group of fetal sheep, adrenal weight increased between 130-135 and 141-145 days (P < 0.05), but there was no change in the abundance of adrenal insulin-like growth factor II (IGF-II) mRNA across this gestational age range. Hypothalamo-pituitary disconnection significantly reduced fetal adrenal weight to 66% that of intact sheep (P < 0.01), but did not alter the abundance of IGF-II mRNA in the fetal adrenal at 140-142 days. 5. Our results suggest that the prepartum changes in adrenal growth and steroidogenesis are under the control of an intact hypothalamo-pituitary axis in late gestation and are dependent on an increase in circulating ACTH(1-39), rather than on ACTH precursors. We have found no evidence, however, for a direct-relationship between fetal adrenal growth or steroidogenesis and adrenal IGF-II mRNA between 130 and 145 days gestation.
Adrenal Glands↗
Effect of profound ischaemia on human muscle: MRI, phosphorus MRS and near-infrared studies.
A pressure cuff was applied to the legs of two human volunteers in order to stop any blood supply for a period of about 30 min. The affected muscle was monitored using proton magnetic resonance imaging (MRI), phosphorus magnetic resonance spectroscopy (MRS) and near infrared (NIR) spectroscopy before, during and after this procedure. The internal temperature of the tissue was also measured. The phase of water protons in muscle showed changes that were not accounted for by the measured temperature, but which correlated with the large increase in deoxyhaemoglobin and deoxymyoglobin observed with NIR as well as the decrease in PCr and increase in Pi observed with MRS. Little or no change was found in proton density or T2*. These results show that in vivo measurements of temperature using the chemical shift method may be confounded by changes in tissue oxygenation. They also show that T2* is an insensitive measure of changes in tissue oxygenation.
Constriction↗
Examples of the design of screened and shielded RF receiver coils.
Three methods of screening RF surface coil receivers are discussed. The aim is to design coils with very much greater sensitivity on one side than on the other so that signal and noise contributions from unwanted regions of the body can be minimized. These methods can usefully be applied to situations wherein data are only wanted from one leg, although the coil is most conveniently located between the two, or from an arm lying adjacent to the body.
Equipment Design↗
An evaluation of the effects of susceptibility changes on the water chemical shift method of temperature measurement in human peripheral muscle.
Divergencies between chemical shift measurements of temperature and directly measured values using optical sensors have been studied in vivo in human peripheral muscle with the assistance of a variety of experimental and theoretical techniques. These include the modelling of both thermal and susceptibility changes using two- and three-dimensional finite element methods, as well as the use of multi-wavelength near-infrared observations. The conclusion of these studies is that a simple temperature calibration is not accessible, with results affected by the complex response of the tissue itself.
Humans↗
Tuned fiducial markers to identify body locations with minimal perturbation of tissue magnetization.
A fiducial marker is described in which a small cell containing a short T1 solution is surrounded by single- or quadrature-tuned windings. It is shown how these can be used to enhance small externally applied RF pulses, which do not significantly perturb the magnetization of the tissue, to excite the fiducial sample, and get substantial signals from it. The fiducials can be used to mark locations on the body unambiguously for, for example, frameless stereotaxy, and to identify coils, catheters, or other inserted devices.
Humans↗
High resolution magnetic resonance imaging of the anal sphincter using a dedicated endoanal coil. Comparison of magnetic resonance imaging with surgical findings.
PURPOSE: To obtain high resolution images of the anal sphincter and adjacent anorectum using an endoanal coil in patients with sepsis, trauma, and low rectal tumors and to compare imaging appearances with findings at time of surgery. PATIENTS AND METHODS: A cylindrical saddle geometry coil (diameter, 9 mm; length, 75 mm) was used to examine 30 patients (mean age, 53.6 years). Pathologies included perianal sepsis (10 patients), obstetric trauma (7 patients), and low rectal tumors (13 patients). Imaging was performed on an 0.5-T Picker Asset or 1.0-T Picker HPQ Vista (Picker International, Highland Heights, OH). T1 and T2 weighted and short inversion time inversion recovery transverse images and T1 weighted coronal images were obtained. Intravenous gadopentetate dimeglumine (0.1 mmol/kg) was given to all patients with suspected infection and neoplasms. RESULTS: Abscesses and fistulas identified using magnetic resonance imaging (MRI) in patients with perianal sepsis were confirmed at surgery in all cases; site of fistulous internal opening into the anal canal was correctly identified in 80 percent of cases. Extent of sphincter tear was correctly assessed on endoanal MRI in all patients with obstetric trauma when compared with surgical findings. Tumor invasion of anal sphincter was seen in 38.5 percent of low rectal carcinomas. CONCLUSIONS: MRI with an endoanal coil provides detailed images of the site and extent of anal fistulas, sphincter tears, and local tumors and is of considerable value in preoperative assessment.
Abscess↗
Magnetic resonance imaging guided breast biopsy using a frameless stereotactic technique.
The high sensitivity but poor specificity of contrast enhanced magnetic resonance (MR) imaging for delineating malignant breast lesions is increasing the demand for MR guide breast biopsy. However, the poor patient access offered by conventional MR systems makes such procedures extremely difficult. We describe a method of performing breast biopsy outside the bore of the magnet using the 3-D MR imaging data. This involves a frameless stereotactic technique using an ultrasonic localizer. The position in space of the tip of a pointer with a handle which incorporates two ultrasound emitters can be tracked using an array of ultrasound detectors. MR visible marker beads (fiducials) placed on the breast and imaged at the same time are identified to the computer in relation to images of the breast. The ultrasonic localizer is used to register the position in space of the fiducials by touching them with the tip of the pointer. The image of the lesion within the breast can then be displayed in relation to the position of the tip of the pointer and the needle approach planned. Nine women with foci of enhancement on their dynamic contrast enhanced MR images underwent frameless stereotactic breast cytology. Needle placement within 2 mm of the lesion was achieved at first pass in eight out of nine (89%) cases: in one case the needle had to be re-positioned prior to sampling. This technique provides a means of targetting MR visible lesions using the MR imaging data whilst performing the procedure outside the magnet bore.
Biopsy, Needle↗
The relative roles of the hypothalamus and cortisol in the control of prolactin gene expression in the anterior pituitary of the sheep fetus.
The neuroendocrine control of prolactin synthesis and secretion before birth is not well understood. We have measured the changes in the level of prolactin mRNA in the anterior pituitary of the fetal sheep throughout the last 15 days of pregnancy (term = 147 +/- 3 days gestation). We have also investigated the effects of surgical disconnection of the fetal hypothalamus and pituitary (HPD) with or without long term cortisol infusion on pituitary prolactin mRNA levels and plasma prolactin concentrations in the late gestation sheep fetus. Prolactin mRNA levels were measured in anterior pituitaries collected from a series of fetal sheep (130-134 days, n = 6; 135-140 days, n = 6; 141-145 days, n = 6) in late gestation. HPD was carried out in ten fetal sheep at 105-115 days gestation and five intact fetal sheep were used as controls. In the HPD group, either saline (HPD + saline group, n = 5) or cortisol was infused (3.5 mg/24 h) for 5 days from 134-136 days gestation (HPD + cortisol group, n = 5). There was an increase in the ratio of prolactin mRNA: 18S rRNA in the fetal pituitary between 130-134 days (0.46 +/- 0.08, n = 6) and 135-140 days (1.27 +/- 0.17 n = 6) which was maintained after 141 days gestation, (1.27 +/- 0.11, n = 6). The mean prolactin mRNA: 18 S rRNA ratio was significantly higher (P < 0.05) in intact fetal sheep (1.41 +/- 0.16, n = 4) than in the HPD fetal sheep after either saline (0.54 +/- 0.14, n = 4) or cortisol (0.74 +/- 0.24, n = 5) administration. The mean plasma concentration of prolactin was also higher in the intact group (28.3 +/- 3.9 ng/ml) when compared with the HPD + saline group (8.0 +/- 3.3 ng/ml) or the HPD + cortisol group (5.6 +/- 1.9 ng/ml). We have demonstrated that there is a strong hypothalamic drive to prolactin synthesis and secretion in the fetus and that cortisol does not act directly at the fetal pituitary to stimulate prolactin synthesis and secretion in late gestation.
Animals↗
Continuous intrafetal infusion of prostaglandin E2 prematurely activates the hypothalamo-pituitary-adrenal axis and induces parturition in sheep.
This study has investigated the effect of continuous intrafetal infusion of PGE2 or saline on hormone concentrations and the length of gestation in sheep. Fetal and maternal vascular catheters were surgically implanted at 112.3 +/- 1.3 days (n = 10), and the infusions were started at 121 +/- 1.2 days of gestation (term = 147). Fetuses were infused with either PGE2 (n = 5; 2 micrograms/min for 48 h and then increased to 4 micrograms/min for the remainder of the experiment) or the vehicle solution (n = 5; sterile isotonic saline) via the fetal carotid artery. In the PGE2-infused group, fetal and maternal plasma PGE2 concentrations increased (P < 0.001) after the change to the higher dose rate (4 micrograms/min) and remained elevated, fetal plasma immunoreactive ACTH (ir-ACTH) concentrations dramatically increased after the start of the infusion being maximal at 11 h before decreasing to match concentrations exhibited by the saline-infused group. Fetal plasma cortisol concentrations increased after the start of the PGE2 infusion (P = 0.05) and increased further after the change to the higher dose rate of 4 micrograms/min (P < 0.001). Concentrations of PGE2, ir-ACTH, and cortisol in the saline-infused group did not change until labor. Plasma concentrations of PGE2 (P < 0.001) and ir-ACTH (P < 0.005) increased on the day of labor in both treatment groups, and fetal cortisol concentrations increased (P < 0.001) in both groups in the last few days before labor. The proportion of low molecular weight ir-ACTH in the plasma of PGE2-infused fetuses was significantly higher than that of saline-infused fetuses (P < 0.001) during the first 15 days of infusion. In the saline-infused group, the proportion of low molecular weight ir-ACTH increased in the last few days before labour (P = 0.001), whereas no change was seen in PGE2-infused fetuses at this time. Maternal plasma progesterone concentrations decreased in both groups in the last few days before labor (P < 0.001). Fetuses infused with PGE2 delivered at 138.4 +/- 2.1 days, whereas control fetuses infused with saline delivered at 148.2 +/- 0.5 days (P < 0.001). The spontaneous increase in PGE2 preceding normal labor may thus play an important role in activation and maturation of the hypothalamic-pituitary-adrenal axis in fetal sheep.
Adrenal Glands↗
Expression of prostaglandin G/H synthase-1 and -2 in ovine amnion and placenta following glucocorticoid-induced labour onset.
Parturition in the sheep is preceded by an increase in the synthesis of prostaglandins by intrauterine tissues. Prostaglandin G/H synthase (PGHS) is the central enzyme involved in prostanoid production. Its expression is enhanced during late gestation in the ewe. Recent studies have identified two PGHS isozymes, termed PGHS-1 and PGHS-2. The labour-associated expression of the two isozymes of PGHS in the sheep has not been characterized. This study investigated the changes in expression of immunoreactive PGHS-1 and PGHS-2 in ovine amnion and placenta following glucocorticoid-induced labour. Ewes underwent surgery to implant fetal and maternal vascular cannulae and uterine electromyogram electrodes between 118 and 125 days of gestation. Fetal sheep were administered either the glucocorticoid betamethasone (n = 5) or saline (control n = 6) by direct transabdominal intrafetal injection. Ewes from the betamethasone-injected group were killed in the first stage of labour as indicated by uterine electromyographic activity. Ewes from the saline-injected group were killed at the same time to obtain age-matched control tissue. The time taken to euthanasia following induced-labour onset in the glucocorticoid-injected animals was 56.6 +/- 0.8 h post-injection. Plasma endocrine profiles in the maternal and fetal circulation following glucocorticoid injection were comparable to those observed following normal spontaneous delivery. At post-mortem, amnion and cotyledons were collected in liquid N2 and stored at -70 degrees C. Solubilized tissue extracts were prepared and analysed by Western blots using polyclonal antibodies to PGHS-1 and PGHS-2 isozymes. Fetal amnion contained PGHS-1 isozyme at day 133 of gestation, as demonstrated in the saline-injected animals. Slightly higher PGHS-1 immunoreactivity was observed following induced-labour onset, although this did not reach statistical significance (P > 0.05). PGHS-2 enzyme was not detectable in amnion. PGHS-2 expression was also not induced following labour onset. In contrast, PGHS-2 demonstrated enhanced expression following glucocorticoid-induced labour in ovine cotyledon. This tissue contained PGHS-1 enzyme, but immunoreactive levels were minimal and demonstrated limited regulation at labour. These data suggest that the previously reported rise in placental PG production at term in the sheep is predominantly due to increased expression of the PGHS-2 isozyme. This suggests that PGHS-2 contributes to PG production at term labour in sheep or is induced by the mechanisms controlling ovine parturition. PGHS-1 isozyme is produced constitutively in ovine amnion and may contribute to the gestational increase in PG formation by intrauterine tissues.
Amnion↗