Professor Geoffrey Donald Thorburn AO, FAA. 2 February 1930-28 October 1996.
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Animals↗
Biomedical subjects
J R Challis
Publications and source records attributed to J R Challis.
Locations and molecular forms of gastrin-releasing peptide-like immunoreactive entities in ovine pregnancy.
Large quantities of gastrin-releasing peptide-like immunoreactivity (GRP-LI) are present in ovine pregnancy fluids (allantoic fluid > fetal plasma > esophageal fluid = amniotic fluid = urine > maternal plasma) and in term endometrium (60 +/- 29 pmol.g-1) and myometrium (4.5 +/- 1.2 pmol.g-1). The larger molecular size [greater than GRP (1-27)] of this GRP-LI entity is not due to a GRP binding protein nor to a C-terminal extension of GRP. In contrast, ovine fetal colon extracts appear to contain the usual GRP (1-27) and GRP (18-27) forms. Hence, the uterus, not the fetus, is the probable source of this novel GRP-like peptide. It apparently acts as a hormone in ovine pregnancy and may play an important role in fetal-placental development.
Amino Acid Sequence↗
Localization and developmental changes in prostaglandin H synthase (PGHS) and PGHS messenger ribonucleic acid in ovine placenta throughout gestation.
In numerous animal species, increased prostaglandin output by intrauterine tissues occurs in association with parturition. In the sheep, prostaglandin H synthase (PGHS) is particularly important in regulating this process, and it has been shown recently that the placental content of the inducible form of the enzyme (PGHS-2) increases during the latter part of gestation whereas no change occurs in the constitutive form (PGHS-1). The purpose of the present study was to examine the distribution of cells containing immunoreactive PGHS-2 and PGHS-2 mRNA in the ovine placenta throughout the second half of gestation (80-147 days). Commercially available antisera to PGHS-2 were used for immunohistochemistry with paraffin-embedded tissues, and a 35S-labeled oligonucleotide probe specific for PGHS-2 mRNA was used for in situ hybridization on frozen sections. Immunohistochemistry indicated that there was an increase in the placental content of immunoreactive PGHS-2 after 140 days gestation. At term, the PGHS-2 was located mainly in the uninucleate trophoblast cells in the placentomes. In situ hybridization showed that the distribution of PGHS-2 mRNA was confined to the trophoblasts, with little or no hybridization signal in the maternal endometrium or the maternal syncytium. Autoradiograms of the sections after in situ hybridization were quantified with a computerized image analysis system. There was an increase in the placental content of PGHS-2 mRNA from around 140 days gestation to term, but no change was found in the level of PGHS-1 mRNA. These studies indicate that an increase in the expression of PGHS-2 occurs in the placental trophoblast tissue near parturition in the sheep. The increase in PGHS-2 mRNA is probably responsible for the increase in PGHS-2 protein and PGHS activity that occurs at this time and may contribute to the large increase in prostaglandin production by the ovine placenta at term.
Animals↗
Pattern of 11 beta-hydroxysteroid dehydrogenase type 1 messenger ribonucleic acid expression in the ovine uterus during the estrous cycle and pregnancy.
The present study was designed to examine the pattern and cellular localization of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) gene expression in the ovine uterus during pregnancy and at 3 mo postpartum. High levels of 11 beta-HSD1 mRNA were detected in the endometrium from Days 60 to 143 (term = 145 days), and the levels did not change significantly during that time. The level of 11 beta-HSD1 mRNA in the endometrium was always much higher than that in the myometrium, in which the mRNA was not readily detectable throughout pregnancy; at 3 mo postpartum, 11 beta-HSD1 mRNA became undetectable in both endometrium and myometrium. Within the endometrium, intense immunoreactive 11 beta-HSD1 was localized exclusively to the luminal epithelium, and the intensity of 11 beta-HSD1 immunostaining closely followed the level of 11 beta-HSD1 mRNA. To determine whether the level of endometrial 11 beta-HSD1 mRNA was related to the status of ovarian function, tissues from non-pregnant animals at different stages of their reproductive cycle were also examined. It was found that 11 beta-HSD1 mRNA was undetectable in the endometrium of cycling animals up to Day 9 of the estrous cycle but was detectable thereafter. Taken together, these results demonstrate that within the ovine uterus the endometrium is always the dominant site of 11 beta-HSD1 gene expression in relation to the myometrium. Furthermore, the expression of 11 beta-HSD1 mRNA in the endometrium is closely related to the status of the reproductive cycle. The mRNA for 11 beta-HSD1 is highly expressed only during pregnancy and in non-pregnant animals during the late luteal phase. Since circulating levels of progesterone are elevated during both of these periods, the present findings suggest a progesterone effect on uterine 11 beta-HSD1 gene expression.
11-beta-Hydroxysteroid Dehydrogenases↗
Effects of long-term hypoxemia on pituitary-adrenal function in fetal sheep.
To test the hypothesis that long-term hypoxemia causes premature activation of the fetal pituitary-adrenal function, we embolized the fetal side of the placenta in pregnant sheep and examined the changes in concentrations of immunoreactive adrenocorticotropic hormone (irACTH), cortisol, and prostaglandin E2 (PGE2) in fetal plasma, and levels and localization of proopiomelanocortin (POMC) mRNA in the pars distalis and the pars intermedia of the fetal pituitary. Twelve fetal sheep were studied (6 embolized and 6 control) for 21 days between 0.74 and 0.88 of gestation. Daily injections of nonradiolabeled microspheres were given into the fetal abdominal aorta to decrease fetal arterial oxygen content by 40-50% of the preembolization values. In the embolized group, concentrations of irACTH, PGE2, and cortisol in fetal plasma increased gradually and were significantly (P < 0.05) elevated above those of controls after day 10, day 16, and day 20, respectively. POMC mRNA levels in the pars distalis of the fetal pituitary were not different from those of controls but were significantly reduced in the pars intermedia (P < 0.05). We conclude that levels of POMC mRNA in the pars distalis are unchanged during long-term hypoxemia possibly because of negative feedback effects of elevated cortisol on the pituitary gland. During long-term fetal hypoxemia, there is a differential regulation of POMC mRNA expression in the pars distalis and pars intermedia.
Adrenocorticotropic Hormone↗
Differential regulation of proopiomelanocortin messenger ribonucleic acid in the pars distalis and pars intermedia of the pituitary gland after prolonged hypoxemia in fetal sheep.
POMC messenger RNA (mRNA) is synthesized and translated to form ACTH in the pars distalis and ACTH-related peptides in the pars intermedia of the pituitary in fetuses of species such as sheep. In the fetal sheep, maturation of hypothalamo-pituitary-adrenal (HPA) function occurs during late pregnancy accompanied by increased levels of POMC mRNA in the pars distalis, and contributes to the stimulus for birth. Activation of fetal HPA function also occurs with short term hypoxemia. However, the effects of more prolonged fetal hypoxemia, which may predispose to premature parturition, on POMC mRNA levels in the pars distalis and pars intermedia are not known. We studied the effects of sustained hypoxemia (48 h) in the absence of acidosis on fetal HPA responses at two times in late gestation, days 126-130 and days 134-136 (term = approximately 145 days). Hypoxemia was induced by lowering the fraction of oxygen in the maternal inspired gas mixture. Fetal arterial oxygen tension fell by 6-8 mm Hg, without a change in fetal arterial pH or carbon dioxide tension. Pituitary POMC mRNA was localized and quantified by in situ hybridization. At both gestational ages, hypoxemia caused a transient elevation in fetal plasma ACTH, with a maximum response at +2 h, and a sustained elevation in circulating cortisol. Cortisol responses were greater in the older fetuses. Changes in plasma cortisol were not associated with alterations in the plasma corticosteroid-binding capacity or in levels of hepatic corticosteroid-binding globulin mRNA. Pituitary POMC mRNA showed a regional distribution in the pars distalis, and mean levels increased with gestational age. After 48 h of hypoxemia, POMC mRNA levels had increased in the pars distalis. The regional distribution was unaffected by the hypoxemic insult. In contrast, POMC mRNA levels in the pars intermedia decreased after hypoxemia, and the reduction was greater in the older fetuses. We conclude that in response to prolonged hypoxemia, there is differential regulation of POMC mRNA levels in the pars distalis and pars intermedia of the pituitary in fetal sheep. The magnitude of these responses also changes with gestational age. The increase in POMC mRNA levels in the pars distalis at 48 h of hypoxemia, despite a rise in plasma cortisol and without a change in corticosteroid-binding globulin, suggests altered regulation of HPA function at this time.
Adrenal Cortex Hormones↗
Gastrin-releasing peptide-like immunoreactivity is present in human maternal and fetal placental membranes.
Extracts of human term amnion, placenta, and chorion/decidual tissue (n = 5) contained gastrin-releasing peptide-like immunoreactivity (GRPLI) in amounts of 4.7 +/- 2.9 (pmol/g wet wt; mean +/- SEM), 3.6 +/- 1.1 and 2.9 +/- 1.5, respectively. Using C-terminally directed antisera and gel filtration chromatography and reverse-phase high-performance liquid chromatography (HPLC), each tissue contained molecular forms consistent with the presence of GRP1-27 and GRP18-27 but also contained larger amounts of two GRPLI peaks, which apparently are novel GRP-like peptides. In contrast, tissue extracts of human fetal lung contained only GRP1-27, GRP14-27, and GRP18-27. Using RT-PCR and specific GRP primers and probes, messenger RNA encoding for GRP was readily demonstrable from 6-weeks gestation throughout pregnancy to term in full-thickness membranes, placental villi, and decidua. Positive immunohistochemical staining for GRP occurred in extravillous trophoblasts in decidual septa and fetal membranes, cytotrophoblasts, syncytiotrophoblast, and certain stromal cells in placental villi and amniotic epithelium. GRPLI and GRP messenger RNA were present from the earliest dates examined (6-9 weeks) throughout pregnancy to term. Given the proven trophic nature of GRP and related peptides, these peptides may play important roles in maternal, placental, and fetal development during human pregnancy.
Amnion↗
The expression of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) genes in the human placenta and membranes: evidence for IGF-IGFBP interactions at the feto-maternal interface.
The placenta synthesizes insulin-like growth factors (IGFs) and their binding proteins (IGFBPs), which are believed to regulate its growth and development in an autocrine/paracrine manner. To delineate the cellular sites of expression of IGP and IGFBP messenger ribonucleic acids (mRNAs) in human placenta throughout pregnancy, we used in situ hybridization histochemistry with 35S-labeled IGF and IGFBP complementary RNA probes on human placentas and fetal membranes of gestational ages 6 weeks to term (40 weeks). In placental regions where trophoblasts (fetal) or decidua (maternal) coexist (e.g. basal plate), the identity was delineated by their cytokeratin or vimentin immunoreactivity, respectively. Except for IGF-II, mRNAs encoding peptides of the IGF system were expressed in a similar spatial pattern and relative abundance throughout gestation. Both IGF mRNAs showed similar tissue distribution, but the IGF-II mRNA was more abundant than IGF-I mRNA at all gestational ages. IGF-II mRNA was expressed in the chorionic mesoderm of placental villi and chorionic plate in moderate abundance, and it decreased with gestation. It was also expressed in the trophoblasts of the cytotrophoblastic shell and Langhan's layer of placental villi only in the first trimester, suggesting an autocrine role for IGF-II in early cytotrophoblastic proliferation and/or differentiation. IGF-II mRNA was expressed most abundantly in the columns of intermediate trophoblasts in the anchoring villi and chorionic and basal plates. A gradient of IGF-II mRNA abundance was observed in the trophoblasts of the cytotrophoblastic column, with greater IGF-II mRNA levels in those at the invading front, suggesting a role for IGF-II in trophoblastic invasion. In the fetal membranes, IGF-II mRNA was identified in the amnion and chorion laeve. IGF-I receptor mRNA was expressed in low abundance in all cell types of the placenta. All six IGFBP mRNAs were identified in variable abundance in the decidualized stromal cells of the maternal decidua basalis and parietalis, with IGFBP-1 mRNA being expressed in the greatest abundance. The spatial pattern of expression of each IGFBP mRNA also differed among decidual cells, with IGFBP-1, IGFBP-2, IGFBP-4, and IGFBP-6 mRNAs being expressed in most cells, whereas IGFBP-3 and IGFBP-5 mRNAs were expressed in only some cells. IGFBP-1 mRNA was expressed initially in the epithelium of endometrial glands and in a population of decidualized stromal cells in early gestation, and subsequently in the majority of decidualized stromal cells. IGFBP-3 mRNA was expressed in both the decidua and certain intermediate trophoblasts of the basal plate and anchoring villi of placenta and in amnion and chorion laeve of fetal membranes. IGFBP-4 and IGFBP-5 mRNA were expressed additionally in low abundance in the chorionic mesoderm. IGFBP-6 was expressed in greater abundance in the decidua parietalis than in decidua basalis, although the general level of expression was low. The spatial pattern and relative abundance of expression of IGFBP mRNAs suggest IGFBP-1 to be the predominant IGFBP synthesized by the maternal decidual cells, interacting with the IGF-II that synthesizes fetal intermediate trophoblasts. Presumably, IGF-II and IGFBPs are used for cell to cell communication between fetal trophoblasts and maternal decidual cells at the feto-maternal interface for placental development and/or function.
Extraembryonic Membranes↗
Regional adrenal blood flow responses to adrenocorticotropic hormone after chronic embolization of the fetal placental circulation in sheep.
To ascertain whether repeated hypoxic stress would alter the response of the adrenal cortex to adrenocorticotropic hormone (ACTH), by premature activation of the hypothalamic-pituitary-adrenal axis, we studied fetal sheep subjected to daily reduction of arterial oxygen content by embolization of the fetal placental circulation with 15 microns microspheres for 8 days from about day 124 of gestation (term approximately 147 days) and sham-embolized controls. Starting before the final embolization (or sham-embolization) on day 8, and continuing for 24 h, the fetus was given an intravenous infusion of ACTH1-24 (0.5 microgram/h) or vehicle. Fetal and maternal blood samples were taken for determination of immunoreactive cortisol, and regional adrenal and fetal placental blood flows were measured by the microsphere technique at three time points: 1 h before infusion, 3 h after the start of the infusion (1 h after embolization), and after 24 h of infusion. Prior to infusion of ACTH or vehicle, fetal placental blood flow was lower in microsphere-embolized fetuses than in sham-embolized controls (199 +/ 15 vs 292 +/- 25 ml/min per 100 g tissue; mean +/- S.E.; P<0.01). However, plasma cortisol and adrenal cortical blood flow did not differ between embolized fetuses and controls. Adrenal vascular responses to the 24-h infusion of ACTH were similar in embolized and sham-embolized fetuses. Adrenal cortical blood flow increased 3-fold (P<0.05) due to decreased vascular resistance (P<0.01), with no change in adrenal medullary blood flow. Thus, while daily embolization of the fetal placental circulation caused a sustained decrease in cotyledonary blood flow, no evidence of altered responsiveness of the adrenal cortex to ACTH was found in these experiments.
Adrenal Glands↗
Immunohistochemical localization of the glucocorticoid receptor in human fetal membranes and decidua at term and preterm delivery.
The human fetal membranes and decidua may be important in the onset and/or progression of human labor by providing prostaglandins for this process. Glucocorticoids have been implicated in the regulation of prostaglandin production by these tissues but to date there is no direct evidence for glucocorticoid receptors (GRs) being present in human intrauterine tissues. The purpose of the present study was to determine, using immunohistochemistry, whether the human fetal membranes and decidua contained GRs; to determine the localization of receptors to the cytoplasm or nuclei, and to examine the content and distribution of the GRs in tissues obtained during pregnancy following preterm labor (< 37 weeks) and at term prior to and following term labor. Term tissues were obtained prior to labor by elective Caesarean section (n = 9) or following vaginal delivery (n = 9). Tissues from 14 patients who delivered preterm but with no clinical evidence of infection were also examined. Cryostat sections were thaw-mounted onto microscope slides. The immunoreactive GRs were visualized with an Elite Vectastain ABC Kit using a polyclonal antibody prepared against a synthetic peptide corresponding to amino acids 346-367 of the human GR. At term, nuclear GRs were found in amnion epithelial cells, mesenchyme and the chorion laeve. GRs were present, but were less defined, in the decidua. A similar distribution was found in the preterm tissues. However, nuclear staining in the amnion epithelial cells, mesenchymal cells, chorion and decidua was more pronounced in tissues obtained following preterm labor. This study provides direct evidence for the presence of GRs in human fetal membranes and decidua, and suggests the possible importance of multiple cell types in the action of glucocorticoids in these tissues.
Amnion↗
Dopaminergic regulation of pituitary function in the late-gestation fetal sheep.
Development of the fetal ovine pituitary is essential for normal maturation and initiation of the parturition process, as well as for orchestrating endocrine responses to stress in utero. Increases in the biosynthesis of ACTH and prolactin (PRL) occur in the late-gestation fetal sheep pituitary. In the anterior lobe (AL) of the pituitary, pro-opiomelanocortin (POMC) biosynthesis and processing are primarily regulated by corticotrophin-releasing hormone and vasopressin. However, POMC in the intermediate lobe (IL) and PRL in the AL are known to be primarily regulated by dopamine, via the D2 receptor, in adult sheep. Because of the importance of ACTH and PRL during gestation we have investigated a potential role of dopamine in the control of both IL melanotrophs and AL lactotrophs and corticotrophs, in late gestation. Catheters were implanted into a maternal femoral artery and vein, fetal carotid artery and jugular vein as well as into the amniotic cavity. At day 130 of gestation, fetuses were infused intravenously with either the specific D2 receptor agonist bromocriptine (n = 5) or vehicle (n = 5), for 5 days. Blood samples were taken throughout the experiment and pituitaries were removed at the end of the treatment period. Bromocriptine caused a significant decrease (> 50%) in POMC mRNA levels in the IL. In contrast, bromocriptine had no significant effect on POMC mRNA levels or distribution in the AL. Fetal arterial ACTH and cortisol concentrations were unaffected by the bromocriptine infusion, compared with vehicle-infused controls. There was a dramatic decrease (> 80%) in plasma PRL concentrations, compared with the control fetuses. However, PRL mRNA levels in the AL were not significantly affected by bromocriptine. In conclusion, we have found that bromocriptine inhibits aspects of both melanotroph and lactotroph function in late-gestation fetal sheep. The data indicate that the fetal pituitary possesses functional D2 receptors in late gestation.
Adrenocorticotropic Hormone↗
Fetal breathing is not inhibited by ethanol exposure during prolonged reduced uterine blood flow.
When prolonged hypoxemia is induced in fetal sheep by reducing uterine blood flow, fetal breathing movements (FBM) return to normal incidence after their initial decrease. Ethanol also inhibits FBM. These experiments were designed to determine the role of fetal oxygenation status in affecting ethanol-induced inhibition of FBM. A 1-h maternal infusion of 1 g ethanol/kg maternal body weight was given to animals following 20 h of reduced uterine blood flow (RUBF; n = 9), as well as to normoxemic (n = 9) fetal sheep, and the effect on FBM, electrocortical activity (ECoG), and electroocular activity (EOG) was determined. In normoxemic fetuses, the incidence of FBM decreased from 26.1 +/- 5.5% to 2.8 +/- 1.6% (p < 0.05) with ethanol, subsequently returning to baseline values over 6 h, but there was no effect of ethanol on FBM incidence in RUBF fetuses (32.8 +/- 9.1%). Ethanol increased the incidence of intermediate ECoG from 16.6 +/- 2.9% to 49.0 +/- 9.8% (p < 0.01) in normoxemic fetuses, but there was no change in RUBF fetuses. We conclude that the adaptive mechanism(s) invoked by fetal sheep during prolonged RUBF abolishes its ability to respond behaviourally to ethanol.
Animals↗
Developmental regulation of preproenkephalin mRNA in the ovine paraventricular nucleus: effects of stress and glucocorticoids.
The opioid peptides have profound effects at several levels within the hypothalamo-pituitary-adrenal (HPA) axis. Activation of fetal HPA function occurs during late gestation, and as part of the fetal adaptive response to stress. Changes in the relative levels, localization and distribution of hypothalamic preproenkephalin (PENK) mRNA in the ovine hypothalamic paraventricular nucleus (PVN) during development were examined by in situ hybridization histochemistry. The effects of fetal hypoxemia applied in the presence or absence of concomitant cortisol, to establish negative feedback potential in late gestation were also investigated. PENK mRNA was present at low levels within the PVN, by d60 (term d147). During mid to late gestation, there was an increase in PENK mRNA levels from d60-80 to d100-120, then reaching a peak at d130-140. Levels then decreased dramatically during the last 5-7 days prior to parturition, but increased again in the newborn lamb. Throughout gestation, PENK mRNA was confined exclusively to the parvocellular region of the PVN. Cortisol infusion induced significant decreases (P < 0.05) in PENK mRNA, in normoxemic fetuses at d135 of gestation. The hypoxemic insult, which is known to stimulate plasma ACTH and cortisol, in these fetuses, did not significantly affect PENK mRNA. There was no significant difference in hypoxemia significantly decreased PENK mRNA compared to the saline-infused normoxemic fetuses. Together, these results indicate that the elevation of endogenous fetal cortisol, that occurs at the end of gestation, may act to inhibit expression of the PENK gene in the hypothalamic PVN of the developing ovine fetus.
Animals↗
Increased fetal plasma prostaglandin E2 concentrations during fetal placental embolization in pregnant sheep.
OBJECTIVE: The purpose of this study was to examine the effect of chronic fetal placental embolization on fetal plasma prostaglandin E2 concentrations. STUDY DESIGN: Fourteen pregnant sheep were studied (seven embolized and seven controls) for 10 days between 0.84 and 0.91 of gestation. Daily injections of nonradioactive microspheres were made to decrease fetal arterial oxygen content by 30% to 35% of preembolization values. RESULTS: In response to repeated embolization, fetal plasma prostaglandin E2 concentrations increased significantly on day 1, declined to near control levels on days 2 to 6, but were significantly elevated again after day 7. Maternal prostaglandin E2 levels remained unchanged throughout the study. Fetal plasma prostaglandin E2 levels increased significantly with decreasing fetal oxygenation when fetal arterial oxygen content was < 2.0 mmol/L. CONCLUSION: We conclude that there is increased production of prostaglandin E2 by the placenta during progressive fetal hypoxemia induced by fetal placental embolization. We speculate that the progressive increase in prostaglandin E2 may be an important hormonal adaptive mechanism to maintain fetal homeostasis during the development of placental insufficiency.
Animals↗
Conference report: placental growth and function.
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Adaptation, Physiological↗
Effect of arginine vasopressin on regional adrenal blood flow and plasma cortisol concentration in fetal sheep.
OBJECTIVE: To determine whether arginine vasopressin (AVP) at plasma concentrations measured during moderate hypoxemia affects adrenal blood flow. STUDY DESIGN: Regional blood flows were measured in 5 unanesthetized normoxemic fetuses (124-128 days' gestation) during a 24-h intravenous infusion of AVP in isotonic saline solution. Another 5 fetuses received an infusion of vehicle. Blood flows were determined before the infusion and at 2 h and 24 h from its onset using radionuclide-labeled microspheres. RESULTS: At 2 h and 24 h of AVP infusion, fetal plasma concentrations of IR-AVP had risen from 4.7 +/- 0.9 pg/ml to 9.8 +/- 1.1 pg/l and 9.4 +/- 0.7 pg/ml, respectively. Thus we achieved plasma concentrations of IR-AVP comparable to those previously reported during moderate hypoxemia. There was no significant effect of treatment on fetal plasma concentrations of immunoreactive adrenocorticotropic hormone (ACTH) or cortisol. AVP infusion significantly decreased fetal heart rate and raised cotyledonary blood flow from 198 +/- 18 ml/min per 100 g to 235 +/- 17 ml/min and 218 +/- 10 ml/min per 100 g at 2 h and 24 h, respectively, from the start of the AVP infusion. Basal values for adrenal medullary and cortical blood flows were similar in the AVP and saline groups, and did not change significantly during the infusions. CONCLUSION: These findings suggest that the rise in adrenal blood flow seen after hypoxemia is not due to a direct action of systemic AVP, but is attributable to other influences, likely including changes in circulating ACTH.
Adrenal Glands↗
Immunoreactive parathyroid hormone-related protein: its association with preterm labor.
OBJECTIVE: Parathyroid hormone-related protein (PTHrP) is a 141 amino acid protein which contains a 1-36 N-terminal domain resembling parathyroid hormone which has smooth muscle relaxant activity and a mid (67-86) domain which reportedly alters placental calcium transport. Using specific antibodies to these regions of PTHrP, the objective of this study was to determine changes in the levels and localization of the peptides in placenta and membranes that might be indicative of their biological activity and role during term and preterm labor. STUDY DESIGN: Placenta and fetal membranes were collected from patients with preterm delivery (PTL) (n = 16), term cesarean section in the absence of labor (n = 10) and term vaginal delivery (n = 5). Immunohistochemistry was performed with specific antisera visualized by the avidin-biotin peroxidase method and the staining intensity was quantified with an image analysis system MCID. RESULTS: Immunoreactive (ir)-PTHrP(1-34) and ir-PTHrP(67-86) were localized to the amnionic epithelium chorionic trophoblasts, decidual cells and placental syncytiotrophoblast. Intense immunostaining was observed for ir-PTHrP(67-86) but not for ir-PTHrP(1-34) in the endothelial lining of the villous capillaries. Ir-PTHrP(1-34) staining was lower in placenta and fetal membranes of PTL patients compared with term cesarean section in the absence of labor (P < 0.05 Mann-Whitney test). In contrast, there was no difference in ir-PTHrP [67-86] staining intensity between delivery categories. CONCLUSION: These results showing differential localization of PTHrP(1-34) and PTHrP(67-86) suggest cell specific processing of PTHrP precursor in the human placenta. Moreover, the changes in ir-PTHrP(1-34) but not ir-PTHr(67-86) with labor are indicative of a particular role for this peptide in the delivery process.
Amnion↗
Corticosteroid-binding globulin (CBG) in fetal development.
In fetal sheep the prepartum increase in plasma cortisol concentration is associated with an increase in high affinity corticosteroid binding activity in plasma. This appears to reflect an increase in corticosteroid-binding globulin (CBG) biosynthesis from the fetal liver, and evidence is presented that hepatic CBG gene expression is increased by exposure to glucocorticoids in the fetus. Immunoreactive CBG is found in other fetal tissues, and CBG mRNA is present in fetal pituitary. CBG reduces the ability of cortisol to exert negative feedback on basal or CRH-stimulated ACTH output by fetal sheep pituitary cells in culture. We suggest that CBG interacts with cortisol in a manner that maintains a low negative feedback on the pituitary, and perhaps hypothalamus. This constitutes a component of the cascade of events that is associated with hypothalamic-pituitary-adrenal activation in the late gestation fetus, and with the onset of parturition.
Animals↗