Late-gestation betamethasone enhances coronary artery responsiveness to angiotensin II in fetal sheep

2004 ◽  
Vol 286 (1) ◽  
pp. R80-R88 ◽  
Author(s):  
Robert D. Roghair ◽  
Fred S. Lamb ◽  
Kurt A. Bedell ◽  
Oliva M. Smith ◽  
Thomas D. Scholz ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Protein Expression ◽  
Late Gestation ◽  
Mesenteric Arteries ◽  
Receptor Protein ◽  
Maximal Response ◽  
Ang Ii ◽  
Fetal Sheep ◽  
Arterial Blood ◽  
Significant Difference

Antenatal glucocorticoids are used to promote the maturation of fetuses at risk for preterm delivery. While perinatal glucocorticoid exposure has clear immediate benefits to cardiorespiratory function, there is emerging evidence of adverse long-term effects. To determine if antenatal betamethasone alters vascular reactivity, we examined isometric contraction of endothelium-intact coronary and mesenteric arteries isolated from twin fetal sheep at 121-124 days gestation (term being 145 days). One twin received betamethasone (10 μg/h iv) while the second twin received vehicle (0.9% NaCl) for 48 h immediately before the final physiological measurements and tissue harvesting. Fetuses that received betamethasone had higher mean arterial blood pressures than the saline-treated twin controls (53 ± 1 vs. 48 ± 1 mmHg, P < 0.05). Coronary vessels from betamethasone-treated fetuses exhibited enhanced peak responses to ANG II (72 ± 17 vs. 23 ± 6% of the maximal response to 120 mM KCl, P < 0.05). There was no significant difference in response of the coronary arteries to other vasoactive compounds [KCl, U-46619, sodium nitroprusside, 8-bromo-cGMP (8-BrcGMP), isoproterenol, and forskolin]. Contractile responses to ANG II were similar in betamethasone and control mesenteric arteries (48 ± 17 vs. 36 ± 12% of the maximal response to 10-6 M U-46619). Western blot analysis revealed AT1 receptor protein expression was increased by betamethasone in coronary but not in mesenteric arteries. These findings demonstrate that antenatal betamethasone exposure enhances coronary but not mesenteric artery vasoconstriction to ANG II by selectively upregulating coronary artery AT1 receptor protein expression.

Early gestation dexamethasone programs enhanced postnatal ovine coronary artery vascular reactivity

2005 ◽  
Vol 288 (1) ◽  
pp. R46-R53 ◽  
Author(s):  
Robert D. Roghair ◽  
Fred S. Lamb ◽  
Francis J. Miller ◽  
Thomas D. Scholz ◽  
Jeffrey L. Segar
Keyword(s):  
Coronary Artery ◽  
Vascular Reactivity ◽  
Mesenteric Arteries ◽  
Receptor Protein ◽  
Ang Ii ◽  
Fetal Sheep ◽  
Early Gestation ◽  
Arterial Blood ◽  
Vascular Responsiveness ◽  
Blood Pressures

Excessive exposure of the fetus to maternally derived corticosteroids has been linked to the development of adult-onset diseases. To determine if early gestation corticosteroid exposure alters subsequent coronary artery reactivity, we administered dexamethasone (0.28 mg·kg−1·day−1) to pregnant ewes at 27–28 days gestation (term being 145 days). Vascular responsiveness was assessed in endothelium-intact coronary and mesenteric arteries isolated from steroid-exposed and age-matched control fetal sheep at 123–126 days gestation and lambs at 4 mo of age. Lambs exposed to maternal dexamethasone had higher mean arterial blood pressures than the age-matched controls (93 ± 3 vs. 83 ± 5 mmHg, P < 0.05). Mesenteric arteries from the steroid-exposed fetuses displayed diminished responses to ANG II, relative to controls. In 4-mo-old lambs, prenatal dexamethasone exposure significantly increased coronary artery vasoconstriction to ANG II, ACh, and U-46619, but not KCl. In contrast, postnatal mesenteric artery reactivity was unaltered by steroid exposure. Compared with fetal mesenteric reactivity, postnatal mesenteric reactivity to ANG II, phenylephrine, and U-46619 was diminished, whereas the response to 120 mmol/l KCl was heightened. Coronary artery ANG II receptor protein expression was not significantly altered by steroid exposure in either age group. These findings demonstrate that early-gestation glucocorticoid exposure programs postnatal elevations in blood pressure and selectively enhances coronary artery responsiveness to second messenger-dependent vasoconstrictors. Glucocorticoid-induced alterations in coronary vascular smooth muscle structure or function may provide a mechanistic link between an adverse intrauterine environment and later cardiovascular disease.

Thyroid hormone modulates renin and ANG II receptor expression in fetal sheep

2005 ◽  
Vol 289 (4) ◽  
pp. R1006-R1014 ◽  
Author(s):  
Kai Chen ◽  
Luke C. Carey ◽  
Nancy K. Valego ◽  
Jingfang Liu ◽  
James C. Rose
Keyword(s):  
Thyroid Hormone ◽  
Receptor Expression ◽  
Late Gestation ◽  
Receptor Subtype ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Active Renin ◽  
Arterial Blood

Fetal renin-angiotensin system (RAS) activity is developmentally regulated, increasing in late gestation toward term. At the same time, fetal hemodynamic parameters change, with blood pressure increasing and heart rate decreasing. During this period, fetal plasma thyroid hormone concentrations also increase significantly. In this study we utilized the technique of thyroidectomy (TX), which removes thyroid hormone from the circulation, to investigate the importance of thyroid hormone on the developmental changes in the RAS (in plasma, kidney, heart, and lung) and hemodynamic regulation in fetal sheep. TX was performed at 120 days of gestational age (dGA), and control fetuses were sham operated. Immediately before necropsy (∼137 dGA), fetuses were infused with isoproterenol and the hemodynamic responses were noted. TX significantly decreased plasma thyroid hormone concentrations and renal renin mRNA and renal active renin levels but did not change fetal plasma active renin levels. TX decreased both angiotensin II receptor subtype 1 (AT1) mRNA and protein levels in kidney and lung but not in the left ventricle. TX also was associated with increased ANG II receptor subtype 2 (AT2) mRNA and protein at the 44-kDa band in kidney, whereas AT2 protein was decreased at the 78-kDa level in kidney and lung tissue only. TX fetuses had significantly lower basal mean arterial blood pressures (MAP) and heart rates than controls. Isoproterenol infusion decreased MAP in TX fetuses. These findings support the hypothesis that thyroid hormone is important in modulating maturation of RAS and cardiovascular function in the late-gestation fetal sheep.

Inhibin and follistatin concentrations in fetal tissues and fluids during gestation in sheep: evidence for activin in amniotic fluid

1994 ◽  
Vol 141 (2) ◽  
pp. 219-229 ◽  
Author(s):  
S Wongprasartsuk ◽  
G Jenkin ◽  
J R McFarlane ◽  
M Goodman ◽  
D M de Kretser
Keyword(s):  
Amniotic Fluid ◽  
Adrenal Glands ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Fetal Sheep ◽  
Fetal Testis ◽  
Cells In Culture ◽  
Tissue Extracts ◽  
Significant Difference ◽  
The Individual

Abstract The concentrations of inhibin and follistatin in amniotic fluid and in tissue extracts from the placenta, gonads and adrenals of fetal sheep were measured using radioimmunoassays. These tissue extracts were from whole fetuses from days 16 to 45 and from the individual organs from day 46 to 145 (term) and were assayed at multiple dilutions. The capacity of these extracts to alter FSH production of rat anterior pituitary cells in culture was also assessed at multiple dilutions. Immunoactive inhibin concentrations in amniotic fluid from both sexes increased during gestation and levels were significantly greater in males than females. Peak concentrations of immunoreactive inhibin of 11·2±1·9 ng/ml were found in males at 116–125 days of gestation. Follistatin concentrations did not change throughout gestation and no significant difference was noted between sexes. Mean follistatin levels throughout gestation were 3·0±0·9 ng/ml for males and 3·7±0·9 ng/ml for females. Despite the potential for FSH inhibition by inhibin and follistatin, amniotic fluid from both sexes at all stages of gestation stimulated FSH secretion in the pituitary cell bioassays, suggesting the presence of activin which was confirmed by the measurement of immunoactive activin (13·3±2·5 ng/ml) in a specific radioimmunoassay. Maximum concentrations of immunoactive and bioactive inhibin in placental extracts were observed in late gestation (2·2 ±0·6 and 3·8±1·6 ng/g respectively) and there was no significant difference between sexes. Follistatin concentrations in placental cotyledons ranged from 11·5 to 27·1 ng/g with no significant difference between sexes. In view of the higher follistatin concentrations compared with inhibin, it is likely that the capacity of placental extracts to suppress FSH production by pituitary cells in culture is due predominantly to follistatin. Immunoactive inhibin was observed in high concentrations in the fetal testis throughout gestation; with concentrations increasing to a maximum of 1993·0± 519·7 ng/g at 126–135 days of gestation with a ratio of bioactive: immunoactive inhibin of 1:20. Although bioactive and immunoactive inhibin was also observed in fetal ovaries and adrenals from both male and female fetuses, concentrations were lower than those observed in fetal testes. Follistatin concentrations in the fetal testis were elevated between 70 and 95 days (97·6 ng/g) and then declined. Similar concentrations were found in the adrenal glands of both sexes (males 83·5–103·3 ng/g: females 55·3–95·8 ng/g). In both males and females, immunoactive inhibin concentrations in fetal adrenals increased during gestation peaking at levels of 34·4±16·5 and 27·8± 9·0 ng/g respectively. These data suggest that the capacity of adrenal extracts to suppress FSH production by pituitary cells is due to both inhibin and follistatin. These studies demonstrated that significant concentrations of immunoactive inhibin and follistatin are present in amniotic fluid, and the fetal gonads, adrenal glands and placenta in sheep. The role of these proteins during fetal development requires further study. Journal of Endocrinology (1994) 141, 219–229

Ovine fetal adrenal gland and cardiovascular function

1988 ◽  
Vol 254 (4) ◽  
pp. R706-R710 ◽  
Author(s):  
N. D. Ray ◽  
C. S. Turner ◽  
N. M. Rawashdeh ◽  
J. C. Rose
Keyword(s):  
Heart Rate ◽  
Adrenal Gland ◽  
Arterial Pressure ◽  
Blood Volume ◽  
Cardiovascular Function ◽  
Late Gestation ◽  
Arterial Blood ◽  
Significant Difference ◽  
Ovine Fetus ◽  
Ovine Fetal

Given the necessity of the adrenal gland in maintaining cardiovascular function in adults of various species, these experiments were conducted to determine if fetal bilateral adrenalectomy results in altered resting heart rate, hypotension, and decreased basal blood volume as well as a diminished ability of the fetus to maintain arterial pressure and restore blood volume in response to hemorrhage. We studied heart rate, arterial blood pressure, and blood volume changes in response to hemorrhage of 20% of blood volume at 2%/min in seven adrenalectomized and six intact chronically cannulated unanesthetized lambs between 119 and 133 days of gestation. Blood volumes and percent restitution of shed volume were determined using 51Cr-tagged red blood cells and changes in hematocrit. There was no significant difference between groups in basal heart rate, mean arterial pressure, hematocrit, and blood volume. The two groups were similar to hemorrhage-induced changes in these and restitution of volume. Therefore, fetal adrenal glands are not necessary for basal cardiovascular function or regulation subsequent to moderate hemorrhage in the late gestation ovine fetus.

scholarly journals Exogenous GH infusion to late-gestational fetal sheep does not alter fetal growth and metabolism

2000 ◽  
Vol 166 (3) ◽  
pp. 591-597 ◽  
Author(s):  
MK Bauer ◽  
JE Harding ◽  
BH Breier ◽  
PD Gluckman
Keyword(s):  
Fetal Growth ◽  
Growth Increment ◽  
Late Gestation ◽  
Placental Lactogen ◽  
Maternal Weight ◽  
Gh Treatment ◽  
Fetal Sheep ◽  
Crown Rump Length ◽  
Gh Secretion ◽  
Significant Difference

The role of GH in the regulation of fetal growth and metabolism in late gestation is not well defined. The aim of this study was to determine the effects of exogenous GH infusion on fetal growth and feto-placental metabolism in the normally growing late-gestation fetal sheep. Eleven fetuses received pulsatile GH infusion (3.5 mg/day) for 10 days while 12 control fetuses received vehicle. The GH infusion was given as a continuous infusion (2.5 mg/day) plus an additional pulsatile component (30 pulses equivalent to 1 mg/day) designed to mimic the natural pattern of GH secretion. Fetal GH infusion raised the circulating fetal concentrations of GH threefold, but did not change fetal concentrations of IGF-I, IGF-binding protein-3, insulin or ovine placental lactogen. GH-treated fetuses had blood urea concentrations 15% lower than controls (P<0.05) and glucose uptake 18% lower per kg fetal weig! ht (P=0.06). There were no other differences attributable to fetal GH infusion in feto-placental metabolism, placental function or placental blood flow. GH-treated fetuses were larger than controls at postmortem (weight+13%, P<0.01; girth+5%, P<0.01; crown-rump length+3%, P<0.05). However, there were no differences between groups in measures of fetal growth (increment in chest girth and hindlimb length). GH-treated fetuses had heavier mothers and when maternal weight was included as a covariate in the analysis, there was no significant difference between treatment groups that could be attributed to GH treatment. GH infusion to normal fetal sheep does not appear to have a significant effect on feto-placental metabolism or fetal growth.

scholarly journals Chronic Intermittent Hypobaric Hypoxia Decreases High Blood Pressure by Stabilizing the Vascular Renin-Angiotensin System in Spontaneously Hypertensive Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Hua Chen ◽  
Bin Yu ◽  
Xinqi Guo ◽  
Hong Hua ◽  
Fang Cui ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Hypobaric Hypoxia ◽  
Renin Angiotensin System ◽  
Mesenteric Arteries ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Tnf Α

Background and AimsPrevious studies have demonstrated the anti-hypertensive effect of chronic intermittent hypobaric hypoxia (CIHH) in hypertensive rats. The present study investigated the anti-hypertensive effect of CIHH in spontaneously hypertensive rats (SHR) and the role of the renin-angiotensin system (RAS) in anti-hypertensive effect of CIHH.MethodsFifteen-week-old male SHR and WKY rats were divided into four groups: the SHR without CIHH treatment (SHR-CON), the SHR with CIHH treatment (SHR-CIHH), the WKY without CIHH treatment (WKY-CON), and the WKY with CIHH treatment (WKY-CIHH) groups. The SHR-CIHH and WKY-CIHH rats underwent 35-days of hypobaric hypoxia simulating an altitude of 4,000 m, 5 h per day. Arterial blood pressure and heart rate were recorded by biotelemetry, and angiotensin (Ang) II, Ang1–7, interleukin (IL)-6, tumor necrosis factor-alpha (TNF)-α, and IL-10 in serum and the mesenteric arteries were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. The microvessel tension recording technique was used to determine the contraction and relaxation of the mesenteric arteries. Hematoxylin and eosin and Masson’s staining were used to observe vascular morphology and fibrosis. Western blot was employed to detect the expression of the angiotensin-converting enzyme (ACE), ACE2, AT1, and Mas proteins in the mesenteric artery.ResultsThe biotelemetry result showed that CIHH decreased arterial blood pressure in SHR for 3–4 weeks (P &lt; 0.01). The ELISA and immunohistochemistry results showed that CIHH decreased Ang II, but increased Ang1–7 in serum and the mesenteric arteries of SHR. In the CIHH-treated SHR, IL-6 and TNF-α decreased in serum and the mesenteric arteries, and IL-10 increased in serum (P &lt; 0.05–0.01). The microvessel tension results revealed that CIHH inhibited vascular contraction with decreased Ang1–7 in the mesenteric arteries of SHR (P &lt; 0.05–0.01). The staining results revealed that CIHH significantly improved vascular remodeling and fibrosis in SHR. The western blot results demonstrated that CIHH upregulated expression of the ACE2 and Mas proteins, and downregulated expression of the ACE and AT1 proteins (P &lt; 0.05–0.01).ConclusionCIHH decreased high blood pressure in SHR, possibly by inhibiting RAS activity, downregulating the ACE-Ang II-AT1 axis and upregulating the ACE2-(Ang1-7)-Mas axis, which resulted in antagonized vascular remodeling and fibrosis, reduced inflammation, and enhanced vascular relaxation.

Blood pressure and heart rate in the ovine fetus: ontogenic changes and effects of fetal adrenalectomy

1999 ◽  
Vol 276 (1) ◽  
pp. H248-H256 ◽  
Author(s):  
Nobuya Unno ◽  
Chi H. Wong ◽  
Susan L. Jenkins ◽  
Richard A. Wentworth ◽  
Xiu-Ying Ding ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Plasma Cortisol ◽  
Time Windows ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Long Term Study ◽  
Arterial Blood ◽  
Ovine Fetus

Ontogenic changes in baseline and 24-h rhythms of fetal arterial blood pressure (FABP) and heart rate (FHR) and their regulation by the fetal adrenal were studied in 18 fetal sheep chronically instrumented at 109–114 days gestation (GA). In the long-term study, FABP and FHR were continuously recorded from 120 days GA to spontaneous term labor (>145 days GA) in five animals. Peak times (PT) and amplitudes (Amp) of cosinor analysis were compared at 120–126, 127–133, and 134–140 days GA. Consistent, significant linear increases in FABP and linear decreases in FHR were observed in all fetuses. Significant 24-h rhythms in FABP and FHR were observed during all the time windows. In the adrenalectomy study, to test the hypothesis that fetal cortisol plays a key role in cardiovascular maturation, fetal adrenals were removed in eight animals (ADX); sham fetal adrenalectomy was performed on five animals (Con). Cortisol (4 μg/min) was infused intravenously in four ADX fetuses from day 7postsurgery for 7 days (ADX+F). No significant changes in PT and Amp in FABP and FHR were observed. Plasma cortisol levels remained low in Con and ADX fetuses (<4.9 ng/ml). Cortisol infusion increased fetal plasma cortisol to 22.3 ± 3.2 ng/ml (mean ± SE) on day 13 in ADX+F fetuses. FABP increased in control and ADX+F but not ADX fetuses; FHR decreased in control and ADX but rose in ADX+F fetuses. These results suggest that, in chronically instrumented fetal sheep at late gestation, 1) increases in FABP and decreases in FHR are maintained consistently from 120 to 140 days GA, with distinct 24-h rhythms, the PT and Amp of which remain unchanged, and 2) the physiological increase in FABP is dependent on the fetal adrenal; bilateral removal of the fetal adrenals does not prevent the ability of cortisol to produce a sustained increase in FABP.

GRF treatment of late pregnant ewes alters maternal and fetal somatotropic axis activity

1991 ◽  
Vol 260 (4) ◽  
pp. E575-E580 ◽  
Author(s):  
M. M. Blanchard ◽  
C. G. Goodyer ◽  
J. Charrier ◽  
G. Kann ◽  
R. Garcia-Villar ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Late Gestation ◽  
Placental Lactogen ◽  
Maximal Response ◽  
Pituitary Cells ◽  
In Vitro Test ◽  
Fetal Sheep ◽  
Igf I

To examine the effects of anabolic agents given during late gestation on the maternal and fetal somatotropic axes, we injected pregnant ewes twice daily with 0.15 mg somatocrinin (GRF)-(1-29) for 10 days beginning on day 130 of gestation. Maternal and fetal endocrine changes were compared with control animals using both in vivo and in vitro approaches. Treatment with GRF increased maternal plasma levels of growth hormone (GH) and insulin-like growth factor I (IGF-I;P less than 0.05) but not IGF-II. Under in vitro test conditions, maternal pituitary cells showed a greater maximal response (P less than 0.001) to GRF. In the fetuses of treated ewes, cord plasma GH levels were not significantly increased compared with controls. These animals had similar IGF-I but higher IGF-II (P less than 0.05) plasma levels. The maximal response of fetal pituitary cells to GRF was increased (P less than 0.001). GRF treatment had no influence on maternal and fetal pituitary cell responses to somatostatin under either basal or GRF-stimulated conditions. In addition, these treatments did not affect plasma levels of placental lactogen, glucose, or free fatty acids in the maternal and fetal sheep. These data are compatible with the hypothesis that treatment of pregnant ewes in the last days of gestation with GRF could support accelerated fetal growth.

What is the Role of Preoperative Breathing Exercises in Reducing Postoperative Atelectasis after CABG?

2019 ◽  
Vol 14 (4) ◽  
pp. 275-279 ◽  
Author(s):  
Seyed Tayeb Moradian ◽  
Amir Abas Heydari ◽  
Hosein Mahmoudi
Keyword(s):  
Coronary Artery ◽  
Coronary Artery Bypass Graft ◽  
Coronary Artery Bypass ◽  
Artery Bypass ◽  
Bypass Graft ◽  
Pulmonary Complications ◽  
Artery Bypass Graft ◽  
Breathing Exercises ◽  
Arterial Blood ◽  
Significant Difference

Background: Atelectasis and hypoxemia are frequently reported after coronary artery bypass graft surgery (CABG). Some studies confirm the benefits of breathing exercises on pulmonary complications, but the efficacy of preoperative breathing exercises in patients undergoing CABG is controversial. In this study, the effect of preoperative breathing exercises on the incidence of atelectasis and hypoxemia in patients candidate for CABG was examined. Methods: In a single-blinded randomized clinical trial, 100 patients who were undergoing coronary artery bypass graft surgery were randomly allocated into two groups of experimental and control, each consisted of 50 patients. Before the operation, experimental group patients were enrolled in a protocol including deep breathing, cough and incentive spirometer. In the control group, hospital routine physiotherapy was implemented. All the patients received the hospital routine physiotherapy once a day for 2 to 3 minutes in the first four days postoperatively. Arterial blood gases and atelectasis were compared between groups. Results: There was no significant difference between groups in terms of atelectasis and hypoxemia (p Value>0.05). Conclusion: Preoperative breathing exercise does not reduce pulmonary complications in patients undergoing CABG.

The effect of fetal hypophysectomy with or without ACTH replacement on the molecular weight profile of enkephalin-containing peptides in the adrenal medulla of the fetal sheep

1992 ◽  
Vol 134 (3) ◽  
pp. 369-375 ◽  
Author(s):  
C. L. Coulter ◽  
I. R. Young ◽  
C. A. Browne ◽  
I. C. McMillen
Keyword(s):  
Molecular Weight ◽  
Adrenal Glands ◽  
Enzymatic Digestion ◽  
Late Gestation ◽  
Fetal Sheep ◽  
Carboxypeptidase B ◽  
Significant Difference ◽  
Group 5 ◽  
Pregnant Ewe

ABSTRACT We have investigated the possible role of the fetal pituitary and ACTH in the control of the synthesis and post-translational processing of the enkephalin precursor, proenkephalin A (proEnk A), in the fetal sheep adrenal gland in late gestation. Fetal hypophysectomy (n = 8) or sham operations (n = 4) were performed between 109 and 118 days of gestation. At 138–139 days, either ACTH(1–24) (10·5 μg/0·24 ml saline per h, n = 4) was infused intravenously for 72 h into hypophysectomized fetal sheep or 0·9% (w/v) NaCl alone (0·24 ml/h, n = 4) was infused for 72 h into hypophysectomized fetal sheep and sham-operated animals. At the end of the infusion the pregnant ewe was killed and left or right adrenal glands (n = 12) were collected from the fetal sheep that were intact and given saline (Intact + sal; n = 4), hypophysectomized and given saline (Hx + sal; n = 4) and hypophysectomized and given ACTH (Hx + ACTH; n = 4). Each adrenal was homogenized in acid (acetic acid (1 mol/l)/HCl (20 mmol/l)/2-mercaptoethanol (0·2%)). After centrifugation, the supernatant was loaded onto a Sephadex G-75 column (2·0 × 50 cm), eluted at 80 ml/24 h and fractions were collected (5 ml, n = 42). An aliquot of each fraction (2 ml) was dried down prior to enzymatic digestion (trypsin/carboxypeptidase B) and oxidation with H2O2, and assay for methionine-O-enkephalin (immunoreactive Met-O-Enk). The total adrenal content of immunoreactive Met-O-Enk was significantly greater in the Hx + ACTH group (326·2 ±66·7 (s.e.m.)ng/adrenal) when compared with either the Intact + sal group (152·7 ±44·0 ng/adrenal) or the Hx + sal group (112·1 ±20·8 ng/adrenal). In the adrenal glands from all fetuses immunoreactive Met-O-Enk was found in four molecular weight ranges: < 12 kDa, 12–7 kDa, 7–3 kDa and < 3 kDa. There was no significant difference between the Hx + sal and Hx + ACTH groups in the proportion of immunoreactive Met-O-Enk present in each of the molecular weight ranges in the adrenals and therefore the data from these groups were combined for further statistical analysis. The proportion of immunoreactive Met-O-Enk in the > 12 kDa range was significantly less in the Intact + sal group (5·5 ±2·3%) when compared with the hypophysectomized sheep with or without ACTH replacement (18·7 ± 4·5%). These data demonstrate that fetal hypophysectomy alters the molecular weight profile of Enk-containing peptides in the adrenal of the fetal sheep and whilst ACTH replacement in the hypophysectomized fetus does not alter the post-translational processing of the Enk-containing peptides, it stimulates an increase in the total amount of immunoreactive Met-O-Enk in the fetal adrenal in late gestation. Journal of Endocrinology (1992) 134, 369–375

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