Biomedical subjects

J R Challis

Publications and source records attributed to J R Challis.

At least 127 records · Page 7Linked to original sources

PubMed1992

Immunohistochemical localization of 3 beta-hydroxy-5-ene-steroid dehydrogenase/delta 5----delta 4 isomerase in human placenta and fetal membranes throughout gestation.

The regulation of steroid production by the placenta and fetal membranes is important for both the maintenance of pregnancy and the timing of parturition. 3 beta-Hydroxy-5-ene-steroid dehydrogenase/delta 5----delta 4-isomerase (3 beta HSD) catalyzes an obligatory step in the biosynthesis of steroid hormones. We have determined the localization of 3 beta HSD in the human placenta, fetal membranes, and umbilical cord throughout gestation by immunohistochemical analysis, using a polyclonal antibody raised in rabbits against a purified preparation of human placental 3 beta HSD. In placenta, immunoreactive (IR-) 3 beta HSD was localized in the syncytiotrophoblast and intermediate trophoblast cells at both villous and extravillous sites, but not in cytotrophoblast cells from 6 weeks gestation to term. At 6-7 weeks gestation, IR-3 beta HSD was distributed in the cytoplasm of syncytiotrophoblast in about half of placental villi. By 12-14 weeks, the syncytiotrophoblast of all placental villi stained positively for 3 beta HSD. In the fetal membranes, strong IR-3 beta HSD staining was found in the trophoblast and reticular layers of chorion and in invasive trophoblast cells in decidua, and weakly in decidual stromal cells and amniotic epithelium. No IR-3 beta HSD was found in amnion on the placental plate, but in the umbilical cord, IR-3 beta HSD was present in the amniotic epithelium and also in fibroblast cells in Warton's jelly. These observations demonstrate that the localization of 3 beta HSD immunoreactivity and, therefore, the presumed sites of delta 5- to delta 4-steroid interconversion throughout gestation are principally the syncytiotrophoblast and intermediate trophoblast cells in placenta and the trophoblast cells in chorion and decidua in fetal membranes.

Extraembryonic Membranes↗

PubMed1992

Immunohistochemical localization of 3 beta-hydroxysteroid/delta 5-delta 4-isomerase, tyrosine hydroxylase and phenylethanolamine N-methyl transferase in adrenal glands of sheep fetuses throughout gestation and in neonates.

Immunoreactive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta-HSD) was localized in adrenal glands of sheep fetuses in cortical-type cells, but not in medullary-type cells, from day 43 of gestation to term and in 2-4-day-old neonates. From day 54 of gestation, the formation of distinct zones within the adrenal cortex was apparent and immunoreactive 3 beta-HSD was found in cortical cells in the zona fasciculata and in groups and cords of cortical cells within the developing medulla, with weak positive staining in the zona glomerulosa. At this stage, most medullary cells were positive for immunoreactive tyrosine hydroxylase, and some of these cells with a juxtacortical distribution also stained positively for immunoreactive phenylethanolamine N-methyl transferase (PNMT). Between days 65 and 130, the adrenal medulla increased in size with little change in the width of the cortex. Organization and zonation of immunoreactive 3 beta-HSD staining cells were evident in the zona fasciculata and in groups of cells in the medulla. Between day 130 and term, uniform immunoreactive 3 beta-HSD staining was found throughout the zona fasciculata, and there was also staining in single cells and small clusters of cells throughout the medulla. At this stage, immunoreactive tyrosine hydroxylase was distributed in most cells throughout the medulla, but in two distinct patterns: cells staining intensely for immunoreactive tyrosine hydroxylase in the central region of the medulla, and cells exhibiting weaker staining for immunoreactive tyrosine hydroxylase localized in a juxta-cortical position. These juxta-cortical cells were also positive for immunoreactive PNMT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1992

Characterization of an ovine glucocorticoid receptor cDNA and developmental changes in its mRNA levels in the fetal sheep hypothalamus, pituitary gland and adrenal.

Fetal sheep tissues possess glucocorticoid receptors (GR), and these change in number during the last two-thirds of gestation. There is, however, no information about developmental changes in tissue GR mRNA levels which might account for alterations in fetal GR content. We have therefore cloned and sequenced a 942 bp GR cDNA from a sheep liver cDNA library, and used it to study the relative abundance of GR mRNA in fetal and neonatal sheep tissues. Analysis of the cDNA revealed a partial sequence of the ovine GR which displayed over 80% identity with residues 143-453 in human GR and 163-472 in rat GR. Furthermore, the first zinc finger motif in these receptors was perfectly conserved among species. The relative abundance of GR mRNA was studied in hypothalami, anterior pituitary glands and adrenals in fetuses at days 60-70, 100-110, 125-130 and at term (approximately 145 days), and in newborn lambs. Total RNA extracts (20 micrograms) were analysed by Northern blot analysis. A single 5.6 kb transcript was detected in all three fetal tissues, and its relative abundance did not change significantly throughout gestation. However, in newborn lambs, levels of GR mRNA increased significantly in the hypothalamus and pituitary gland but decreased to undetectable levels in the adrenal. These tissue-specific changes in the relative abundance of GR mRNA did not correlate with alterations in GR content in fetal tissues, which suggests that the latter may reflect alterations in GR mRNA translation, subsequent modifications and/or GR turnover. In addition, the pattern of developmental changes in GR mRNA content of the adrenal differs from that of the hypothalamus and pituitary gland in neonatal lambs, and indicates that tissue-specific factors may influence GR gene expression in neonatal sheep.

Adrenal Glands↗

PubMed1992

Adrenocorticotrophin responses to hypoxaemia in fetal sheep are sustained in the presence of naloxone.

We have examined the effects of fetal hypoxaemia, produced by reducing the percent oxygen in maternal inspired air, on fetal plasma concentrations of corticotrophin releasing hormone (CRH), adrenocorticotrophin (ACTH) and cortisol and determined the effects of an opioid receptor antagonist, naloxone on these responses. Hypoxaemia (fetal PO2, 15-18 mmHg) for 60 min provoked a significant (P < 0.05) increase in fetal plasma ACTH and cortisol concentrations at days 125-130 of pregnancy, but did not affect circulating CRH. There was no effect of naloxone administered either intravenously (1.25 mg bolus followed by a 2.5 mg/h continuous infusion for one hour; fetal body weight approximately 2.5 Kg) or via the lateral cerebral ventricle (50 micrograms bolus followed by a 100 micrograms/h infusion for one hour) on this pattern of ACTH and cortisol change nor on the lack of CRH response to hypoxaemia. We conclude that the increase in fetal ACTH and cortisol in response to acute hypoxaemia is not accompanied by an increase in systemic CRH concentrations, nor is the response dependent on short-term opioid regulation.

Adrenocorticotropic Hormone↗

PubMed1991

Immunohistochemical localization of prostaglandin H synthase in the sheep placenta from early pregnancy to term.

Prostaglandin H synthase (PGHS) activity within intrauterine tissues is considered to catalyze a critical step in prostaglandin (PG) biosynthesis at parturition. In sheep, the placenta is a major site of PG production throughout pregnancy, but little information is available concerning the cells that are responsible. Therefore we determined the distribution of immunoreactive (IR-) PGHS in ovine placental tissue obtained at different times of pregnancy using immunohistochemical techniques. In placentomes from early pregnancy (Days 30-54), IR-PGHS was present in maternal epithelial syncytium, but was not detectable in trophoblast cells. Between Day 54 and Day 100, the number of cells that stained positive for PGHS declined in the maternal epithelial layer in the body of the placenta, but IR-PGHS was present in maternal epithelial cells overlying the vascular cones of the placental hemophagous zone. It was also present in the chorionic fibroblasts, but remained undetectable from all classes of trophoblast cells. IR-PGHS was first detectable in the trophoblastic epithelium by Day 114. Between Day 119 and term the trophoblast mononuclear epithelial cells were intensely immunopositive for PGHS, although immunonegative binucleate cells were present. The maternal epithelium was immunonegative except during the last 7-10 days of pregnancy when PGHS immunostaining appeared in both basal and apical regions of the placenta. Thus, the cellular localization of IR-PGHS changes during ovine pregnancy, from predominantly maternal during the first half of gestation to undetectable and then to predominantly trophoblastic between Day 114 and term, suggesting a gestation-dependent change in sites of PG production during ovine pregnancy. Appearance of IR-PGHS in the trophoblast precedes activation of the fetal hypothalamic-pituitary-adrenal axis, generally considered to provide the trigger to the onset of parturition in sheep, and would therefore appear to be regulated through alternative pathways or mechanisms.

Animals↗

PubMed1991

DNA synthesis is reduced in selected fetal tissues during prolonged hypoxemia.

The effects of 24 h of reduced maternal uterine blood flow (RUBF) on relative DNA synthesis rates in different tissues and on blood glucose and lactate concentrations were studied in fetal sheep. In six sheep, RUBF was induced for 24 h, whereas in another six sheep (controls), uterine blood flow was not reduced. To estimate DNA synthesis rate, [3H]thymidine (1 mCi/kg) was injected intravenously into each fetus 8 h before the end of the 24-h experimental period. Fetal arterial oxygen saturation decreased from 59.1 +/- 3.3 to 25.7 +/- 5.6% after 1 h of RUBF and remained significantly reduced for the duration of the experiment. Fetal blood lactate concentrations were significantly increased by RUBF from 14.3 +/- 6.5 to 57.8 +/- 12.4 mg/dl at 1 h and remained elevated, whereas fetal blood glucose concentrations were not affected. A 24-h period of RUBF did not significantly alter fetal body weights, tissue weights, tissue-to-body weight ratios, or tissue DNA content. Over the last 8 h of the 24-h experimental period, RUBF was found to significantly reduce the relative rate of DNA synthesis (as assessed by [3H]thymidine incorporation into DNA) in the lung (104.7 +/- 26.6 vs. 17.1 +/- 3.1 dpm/micrograms DNA), quadriceps muscle (92.8 +/- 20.7 vs. 14.4 +/- 5.3 dpm/micrograms DNA), and thymus gland (87.5 +/- 7.1 vs. 32.9 +/- 12.2 dpm/micrograms DNA). Relative DNA synthesis rates in the fetal liver, kidney, small intestine, cerebral cortex, cerebellum, placenta, thyroid gland, and adrenal gland were not significantly affected by RUBF. In this study, we have shown that DNA synthesis was greatly reduced in selected fetal tissues (lung, quadriceps muscle, and thymus gland) by a 24-h period of RUBF, although it is not known why a reduction was only observed in these tissues.

Adrenal Glands↗

PubMed1991

Effect of adrenocorticotropin administration on the biosynthesis of corticosteroid-binding globulin in fetal sheep.

Parturition in sheep is initiated by the fetus through activation of the fetal hypothalamic-pituitary-adrenal axis and is associated with increased concentrations of ACTH, cortisol, and corticosteroid-binding globulin (CBG) in the fetal circulation during the final 10-15 days of pregnancy. Premature parturition and a precocious elevation in fetal plasma CBG are produced by intrafetal ACTH administration, but the possible sources of CBG in the ovine fetus are not known. To determine these sites, CBG mRNA was measured in tissues from fetal sheep in late pregnancy and after intrafetal ACTH treatment, using a sheep CBG cDNA. Fetal ACTH treatment caused a significant increase in the fetal plasma corticosteroid-binding capacity (CBC), although there was no significant difference in CBC between umbilical arterial and umbilical venous plasma. After ACTH treatment, CBC was elevated in fetal liver and kidney. Cortisol binding in these tissues had characteristics similar to those of cortisol binding in fetal sheep plasma. By Northern blot analysis a single mRNA (1.7 kilobases) for CBG was detected in fetal liver, kidney, lung, and adrenal, but not in placenta. The abundance of CBG mRNA in the fetal liver was greater than that in other tissues, but was unchanged by ACTH treatment. The level of CBG mRNA in the fetal kidney, but not in other tissues, increased 3-fold after ACTH. We conclude that the elevation in plasma CBC after intrafetal ACTH, and presumably also at term pregnancy, does not reflect production of CBC by the placenta or transfer from the mother. Rather, it results from production primarily in the fetal liver and kidney, although only in the latter tissue is CBG mRNA accumulation increased by intrafetal ACTH treatment.

Adrenal Glands↗

PubMed1991

The localization and distribution of corticotropin-releasing hormone in the human placenta and fetal membranes throughout gestation.

Using immunohistochemical techniques, we have determined the localization and distribution of CRH immunoreactivity (CRH-IR) in the human placenta, fetal membranes, decidua, and umbilical cord. Tissues were obtained at 6-8 weeks of pregnancy, at term, in association with premature birth, and from patients with pregnancy-induced hypertension or diabetes mellitus. A polyclonal antibody to the epithelial cell marker cytokeratin was used to identify trophoblast cells. CRH-IR was not detected in placenta or decidua at 6-8 weeks gestation. In tissues obtained after idiopathic premature delivery after 21 weeks gestation, positive CRH staining was found in placenta in syncytiotrophoblast and intermediate trophoblast, but not cytotrophoblast. CRH-IR was present in intermediate trophoblast cells that had invaded maternal blood vessels in decidua basalis. In the fetal membranes, CRH-IR was localized in the epithelium and subepithelial cells of amnion, in the trophoblast layer, in some cells of the reticular and cellular layers of chorion, and in some stromal cells and invasive trophoblast cells of decidua. CRH-IR was found in the amniotic epithelium of the umbilical cord and in the musculature of the umbilical vessels. This pattern of distribution of CRH-IR was found in tissues from 21 weeks gestation to term and postterm, and was similar in tissues examined from patients with pregnancy-induced hypertension and diabetes mellitus. These results show clearly that in placenta and membranes, CRH is localized primarily to syncytiotrophoblast and intermediate trophoblast, but not to cytotrophoblast cells. We suggest that the localization of CRH-IR is consistent with CRH affecting paracrine/autocrine interactions within the placenta, fetal membranes, and decidua that may be involved in the maturation of the fetal hypothalamic-pituitary-adrenal axis and in the stimulus and maintainance of labor.

Amnion↗

PubMed1991

Immunoreactive adrenocorticotrophin is present in the ovary and in particular the oocyte of several mammalian species.

Proopiomelanocorticotrophin (POMC)-derived peptides have been identified in both male and female reproductive systems. However, there have been few reports of ACTH, the major biologically active POMC product, in the mammalian ovary. We sought evidence for the presence and localization of immunoreactive (ir)-ACTH in ovaries from sheep, humans, cows, pigs, rats and cats using immunohistochemical techniques. Tissue sections were stained with diaminobenzidine following incubation with a primary antibody raised against ACTH1-24. There was positive staining for ACTH in cells scattered throughout the interstitium of ovaries from all species examined. Immunoreactive ACTH was observed in the oocytes of ovaries from humans, cows, pigs, pregnant and non-pregnant sheep, but not from cats or rats. Positive staining of oocytes was associated with all tertiary and secondary follicles, and some primary follicles. There was no apparent difference in the pattern of staining between pregnant and non-pregnant sheep. Staining for ir-ACTH was absent in ovaries from fetal sheep. We conclude that ir-ACTH is present in ovarian tissue, and in particular the oocyte, from several species of mammal. The presence of ir-ACTH within the oocyte is dependent on species and stage of follicular maturation.

Adrenocorticotropic Hormone↗

PubMed1991

Characteristics and developmental changes of corticotrophin-releasing hormone-binding sites in the fetal sheep anterior pituitary gland.

The responses of the fetal sheep pituitary to corticotrophin-releasing hormone (CRH) change during gestation with maximum output of ACTH around days 120-130, and decreased ACTH output near term. However, there is no information available concerning the extent to which these responses may be modulated by alterations in the number of CRH receptors. Therefore we measured specific CRH-binding sites, and changes in binding characteristics in membrane preparations from fetal sheep anterior pituitaries collected at days 65-70, 85-88, 100-110, 125-130 and at term (approximately 145 days). Binding assays were carried out using 125I-labelled Tyr-ovine CRH (125I-Tyr-oCRH), incubated with crude membrane fractions for 90 min at 22 degrees C. Binding was time- and temperature-dependent, linear with protein concentration, saturable and specific for oCRH. Scatchard analysis of binding data for individual tissues revealed a single class of CRH-binding sites with high affinity (Kd congruent to 1 nmol/l) that did not change significantly with gestational age. However, the number of CRH-binding sites increased progressively from days 65-70 to a maximum at days 125-130, then decreased at term. These results demonstrate the presence of specific CRH-binding sites in the fetal sheep anterior pituitary. Furthermore, the change in CRH receptor number with advancing pregnancy follows a similar time-course to the changes reported previously in responsiveness of the fetal sheep anterior pituitary to exogenous CRH stimulation in vivo. These results suggest that alterations in CRH receptor number may contribute to changes in responsiveness of the fetal sheep anterior pituitary to CRH during gestation.

Adrenocorticotropic Hormone↗

PubMed1991

Pro-opiomelanocortin messenger RNA levels increase in the fetal sheep pituitary during late gestation.

Plasma levels of ACTH and cortisol in fetal sheep increase progressively during late pregnancy, providing the stimulus for birth. However, little information is available concerning either sources of pro-opiomelanocortin (POMC, the precursor to ACTH) or changes in POMC gene expression, which may be responsible for the elevated fetal plasma ACTH concentrations. We therefore studied the relative amount of POMC mRNA in fetal sheep hypothalami, anterior pituitaries and adrenals at discrete times of pregnancy between day 60 and term (approximately 145 days) and from newborn lambs. Total RNA from these tissues was analysed by Northern blot hybridization using a human POMC DNA probe, and the amount of POMC mRNA was expressed relative to the signal obtained for 18S ribosomal RNA. A single 1.2 kb transcript was detected by day 60 in the anterior pituitary, and its relative amount did not change significantly until after days 125-130. Pituitary POMC mRNA levels increased significantly at days 138-143, remained elevated at term and increased further in newborn lambs. In contrast, POMC mRNA was undetectable in hypothalami and adrenal glands of fetuses at all ages. The results suggested that the prepartum rise in plasma ACTH concentrations in fetal sheep is due to increased POMC biosynthesis in the fetal pituitary. The increase in POMC mRNA occurs at a time when fetal plasma cortisol concentrations are elevated, indicating that the negative feedback effects of circulating glucocorticoids on the fetal hypothalamic-pituitary axis may be obscured by other mechanisms that increase pituitary POMC mRNA accumulation during the last week of gestation.

Adrenal Glands↗

PubMed1991

Opioid receptors are present in the hypothalamus but not detectable in the anterior pituitary of the developing ovine fetus.

Exogenous opioids stimulate adrenocorticotropic hormone (ACTH) release in fetal sheep after day 125 of pregnancy (term 145 days), but not at day 110. To determine if the different response is due to an alteration in opioid-binding sites and to examine sites of opioid action on ACTH release, we established an in vitro binding assay to study changes and characteristics of opioid receptor binding sites in ovine fetal hypothalamus and pituitary during development. [3H]-naloxone was used as the radiolabelled ligand. The binding of [3H]-naloxone to hypothalamic membrane preparations was specific, saturable with respect to [3H]-naloxone concentration, and linear with the hypothalamic membrane protein content. Binding assays were conducted on tissues collected from fetuses at three gestational ages: days 110-115 and 125-130 and term. In all cases, Scatchard analysis revealed a single class of binding sites with high binding affinity (0.9-1.2 nM) which did not differ significantly with gestational ages. The binding capacity increased significantly from 45.4 +/- 2.5 fmol/mg protein at days 110-115 to 76.8 +/- 2.3 fmol/mg at days 125-130, but did not change further in term fetuses. When anterior pituitaries from the three groups of fetuses were processed and analyzed in a similar manner, no detectable binding was found. These results indicate (1) that endogenous opioid peptides may act at the hypothalamus rather than pituitary to regulate hypothalamic-pituitary-adrenal activity in the ovine fetus, and (2) the developmental changes in the binding capacity may contribute, in part, to the altered ACTH response reported in previous in vivo studies.

Adrenocorticotropic Hormone↗

PubMed1991

Effect of acutely-induced lactic acidemia on fetal breathing movements, heart rate, blood pressure, ACTH and cortisol in sheep.

Experiments were conducted in 8 chronically-catheterized fetal sheep at 125-135 days gestation in order to determine the effect of exogenously administered lactic acid to the fetus on fetal heart rate, blood pressure, breathing movements (FBM), electrocortical activity (ECOG), plasma immunoreactive (IR-ACTH) and cortisol concentrations. When fetal arterial pH decreased from 7.37 +/- 0.01 during the control period to 7.20 +/- 0.01, there was an initial bradycardia followed by tachycardia but no change in blood pressure. The amplitude of FBM increased 2-fold initially in association with an increase in PCO2 from 47.9 +/- 2.1 mmHg to 58.8 +/- 3.6 mmHg at 5 min into the lactate infusion. There was no change in the incidence of FBM or low-voltage ECOG and there was no change in the plasma concentrations of IR-ACTH and cortisol with the infusion of lactate. We conclude that the major effects of acutely elevating circulatory lactate concentrations in fetal sheep are to increase the amplitude of FBM and to cause an initial bradycardia followed by a tachycardia.

Adrenocorticotropic Hormone↗

PubMed1990

Immunocytochemical distribution and localization of 15-hydroxyprostaglandin dehydrogenase in human fetal membranes, decidua, and placenta.

Biochemical studies have shown the presence of type I oxidized nicotinamide-adenine dinucleotide-dependent 15-hydroxyprostaglandin dehydrogenase in human fetal membranes, decidua, and placenta. However, the localization of prostaglandin dehydrogenase within these tissues is not known. Because the distribution of prostaglandin dehydrogenase may affect the concentration of prostaglandins that reach the myometrium, we used immunocytochemistry to localize immunoreactive prostaglandin dehydrogenase in fetal membranes and placenta. We also examined whether this distribution changed with labor. Tissues were collected at term elective cesarean section or after term spontaneous labor and delivery, were fixed, embeded, and sectioned at 5 microns. Immunoreactive prostaglandin dehydrogenase was determined with a polyclonal primary antibody to human placental prostaglandin dehydrogenase and visualized with the avidin-biotin procedure. Epithelial and epithelium-derived cells were identified by positive staining with a polyclonal antikeratin primary antibody. Cytokeratin staining was observed in amniotic epithelium, trophoblast layer of chorion, invading trophoblast in decidua, and all subsets of trophoblast in the placenta. Immunoreactive prostaglandin dehydrogenase was localized to the trophoblast layer of chorion, invading trophoblast in decidua, and in syncytiotrophoblast and intermediate trophoblast but not cytotrophoblast in the placenta. In chorion, approximately 50% to 60% of the nonvacuolated trophoblast cells stained positively for prostaglandin dehydrogenase. There was no change in the localization of immunoreactive prostaglandin dehydrogenase in any tissue in association with labor.

Amnion↗

PubMed1990

Threshold of hormonal and biophysical responses to acute hypoxemia in fetal sheep at different gestational ages.

We examined whether there was a threshold for change in fetal arterial PO2 to elicit alterations in plasma adrenocorticotropic hormone, arginine vasopressin, or cortisol, or to affect the incidence of fetal breathing movements or eye movements and we determined whether such a threshold changed with gestational age. Fetal sheep were exposed to two levels of hypoxemia, mild (4.6-5.3 mmHg PO2 drop) and moderate (8.3-8.8 mmHg PO2 drop) (1 mmHg = 133.322 Pa) for 1 h without pH change at 125-129 or 134-147 days of gestation within 7 days of spontaneous labor. Hypoxemia was induced by altering the inspired percent oxygen of the mother. No significant hormonal and biophysical changes were observed in mild hypoxemia at either age. In moderate hypoxemia at 125-129 days of gestation, there were significant increases of fetal adrenocorticotropic hormone, arginine vasopressin, and cortisol concentrations, and a decreased incidence of fetal breathing movements and eye movements. At 134-147 days of pregnancy, moderate hypoxemia induced a significant increase in adrenocorticotropic hormone, but the response was less than at 125-129 days of gestation. The arginine vasopressin response was similar to that at 125-129 days and there was no significant change in cortisol. There was a significant decrease in fetal breathing movements but not in eye movements. We conclude that a threshold of fetal arterial PO2 drop exists between 5 and 8 mmHg to elicit endocrine or biophysical responses to hypoxemia in fetal sheep at 125-129 days of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1990

Hormonal and biophysical responses to acute hypoxemia in fetal sheep at 0.7-0.8 gestation.

We examined whether there was a minimal change in fetal arterial Po2 necessary to elicit alterations in plasma adrenocorticotropic hormone, arginine vasopressin, or cortisol or to affect the incidence of breathing movements or eye movements in fetal sheep at 106-117 days of gestation. Fetal sheep were exposed to two levels of hypoxemia, mild (4.1 mmHg Po2 drop) (1 mmHg = 133.32 Pa) and moderate (8.4 mmHg Po2 drop), for 1 h without acidemia. Hypoxemia was induced by altering the inspired percent oxygen of the mother. No significant hormonal and biophysical changes were observed in mild hypoxemia. In moderate hypoxemia, there were significant increases of fetal adrenocorticotropic hormone and arginine vasopressin and decreased incidence of fetal breathing movements. However, there were no significant changes in cortisol or eye movements. We conclude that a fetal arterial Po2 drop of between 4.1 and 8.4 mmHg is necessary to elicit responses to hypoxemia in fetal sheep at 106-117 days of gestation in adrenocorticotropic hormone, arginine vasopressin, and fetal breathing movements, but this degree of hypoxemia does not cause changes in cortisol or fetal eye movements.

Adrenocorticotropic Hormone↗

PubMed1990

Relationship between blood gas values and hormonal response to acute hypoxemia in fetal sheep.

We examined the relationship of fetal plasma immunoreactive adrenocorticotropic hormone (IR-ACTH), arginine vasopressin (AVP) and cortisol to fetal arterial pO2 (PaO2), oxygen saturation (SaO2), change (delta) in PaO2 (delta PaO2) or SaO2 (delta SaO2) in fetal sheep at 125-139 days of gestational age. Fetal sheep were exposed to two levels of hypoxemia induced by altering the inspired percent oxygen to the mother for 1 h without fetal acidemia. Fetal carotid arterial IR-ACTH, AVP and cortisol concentrations during hypoxemia were correlated with fetal PaO2, SaO2, delta PaO2 and delta SaO2 by applying simple regression analysis. For IR-ACTH, a strong correlation was obtained with SaO2, delta SaO2 and delta PaO2 after log transformation to IR-ACTH. For AVP, strong correlation coefficients were obtained with delta SaO2, SaO2, delta PaO2 and PaO2 after reciprocal transformation to AVP, but for cortisol a strong correlation was obtained only with delta PaO2 after log transformation to cortisol. We conclude that during fetal hypoxemia without acidemia, there is a strong correlation between IR-ACTH and SaO2, delta SaO2, delta PaO2 but not PaO2, between AVP and delta SaO2, SaO2, delta PaO2, or PaO2, and between cortisol and delta PaO2.

Acute Disease↗

PubMed1990

Effects of corticotropin-releasing hormone and adrenocorticotropin on prostaglandin output by human placenta and fetal membranes.

We have examined the possibility that corticotropin-releasing hormone (CRH) and adrenocorticotropin (ACTH) might affect prostaglandin (PG) E2 and PGF2 alpha output by term placenta, amnion and decidua during short-term (48-hour) culture, and that effects of CRH might be mediated by ACTH. In all three tissues PG output was stimulated by both CRH and ACTH. These effects were inhibited in the presence of antisera to CRH and to ACTH. Moreover, in placenta, but not in amnion or decidua, the stimulatory effects of CRH on PGE2 and PGF2 alpha output were attenuated in the presence of an antibody to ACTH. Our results support the possibility of paracrine stimulation by CRH and ACTH of PG production in intrauterine tissues, and suggest that in part the effects of CRH on placental PG output might be mediated through ACTH.

Adrenocorticotropic Hormone↗