Biomedical subjects

J R Challis

Publications and source records attributed to J R Challis.

At least 181 records · Page 10Linked to original sources

PubMed1987

The relationship between fetal breathing movements and prostaglandin E2 during ACTH-induced labour in sheep.

We measured fetal breathing movements and fetal carotid arterial prostaglandin E concentrations during adrenocorticotrophin-induced labour in 6 pregnant sheep and in 6 control animals starting at day 127. The 6 ACTH-treated animals went into labour on average 97 h after the onset of infusion and the incidence of fetal breathing movements diminished during the last 12h before the onset of labour. There was a significant negative relationship between the incidence of fetal breathing movements and fetal carotid arterial prostaglandin E concentrations (r = -0.88; P less than 0.001) in ACTH treated animals. These data suggest a role for prostaglandin E in the diminution of fetal breathing movements prior to the onset of labour.

Adrenocorticotropic Hormone↗

PubMed1987

Effects of maternal indomethacin administration on fetal breathing movements in sheep.

To determine the role of prostaglandins in the control of fetal breathing movements, we infused indomethacin (5 mg/ml; 25 mg/kg per day) into the maternal femoral vein for 70 h in 5 pregnant ewes. There was a significant increase in the incidence and amplitude of fetal breathing movements beginning within 2 h reaching a peak at 8-10 h. It then diminished and was no longer present by 20-70 h despite continued indomethacin infusion. Maternal glucose concentrations were increased at 8 and 16 h following the initiation of indomethacin infusion. The data suggested that the previously reported effects of cyclo-oxygenase inhibitor on fetal breathing movements are transient and do not continue beyond 20 h.

Animals↗

PubMed1986

Substrate utilization for estrogen synthesis by human fetal membranes and decidua.

We have investigated the ability of tissue explants of human amnion, chorion, and decidua to produce estrone when incubated alone or in the presence of estrone sulfate, dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, or testosterone. Amnion produced very little estrone from any substrate. Chorion utilized all substrates and decidua utilized estrone sulfate and dehydroepiandrosterone sulfate for estrone production. For both chorion and decidua, estrone sulfate was quantitatively the most important substrate. Chorionic tissues obtained after spontaneous labor produced greater levels of estrone than tissues obtained before labor (p less than 0.05). We could demonstrate no effect of cortisol, estriol, progesterone, prostaglandins, oxytocin, or dibutyryl cyclic adenosine monophosphate on estrogen production. We also measured endogenous concentrations of estrone and estradiol in fetal membranes. We found no significant difference in tissue concentrations between the two methods of delivery. There was no significant correlation between estrone and estradiol concentrations and distance from the placenta. We conclude that human chorion and decidua can produce estrogen, which may have some role in determining the timing of parturition.

Androstenedione↗

PubMed1986

Plasma adrenocorticotropic hormone and cortisol and adrenal blood flow during sustained hypoxemia in fetal sheep.

We examined the effect of sustained hypoxemia with progressive acidemia on pituitary-adrenal endocrine function (adrenocorticotropic hormone, cortisol) and on adrenal blood flow in fetal sheep. Hypoxemia was induced by the maternal sheep breathing a gas mixture containing 9% oxygen, with 3% carbon dioxide added. Induced hypoxemia resulted in a progressive fetal metabolic acidosis but with little change in maternal pH. During induced hypoxemia there was little change in maternal plasma adrenocorticotropic hormone or cortisol level. Fetal adrenocorticotropic hormone and cortisol increased to peak values within 2.8 hours of induced hypoxia but by 7.2 hours had begun to fall to values that were not significantly different from those at 1.4 hours. Fetal adrenal blood flow (microsphere technique) also increased significantly and remained elevated throughout the duration (7.2 hours) of hypoxemia. The maximum fetal adrenal blood flow achieved during hypoxemia was significantly correlated with the basal (prehypoxemia) flow to the adrenals. We conclude that the changes in fetal adrenocorticotropic hormone, cortisol, and adrenal blood flow seen in short-term hypoxemia are reproduced during sustained hypoxemia with acidemia. Furthermore, the noted rise in the fetal adrenocorticotropic hormone level may be an important factor contributing to the increase in adrenal blood flow during hypoxemia.

Adrenal Glands↗

PubMed1986

Changes in prostaglandin transfer across human fetal membranes obtained after spontaneous labor.

Increased prostaglandin E2 production from amnion is thought to be a critical step in the initiation of human parturition. However, it is not known whether amniotic prostaglandin E2 can reach the decidua and/or myometrium. We examined whether prostaglandin E2 could cross the amnion and full-thickness membranes and whether this capacity changed with active labor. Using an in vitro system we found that there was a time-dependent cumulative transfer of total radioactivity and of radioactivity corresponding chromatographically to prostaglandin E2 across amnion and full-thickness membranes. The rate of transfer across the amnion was faster than across full-thickness membranes and varied according to the site of tissue sampling within the uterus. The permeability constant for prostaglandin E2 transfer across full-thickness membranes was significantly higher in tissue collected after the spontaneous onset of labor than in tissue collected at elective cesarean section at term. We conclude that prostaglandin E2 produced in human amnion at term may escape metabolism in the chorion and reach the decidua and/or myometrium.

Decidua↗

PubMed1986

Ovine fetal adrenal maturation at term and during fetal ACTH administration: evidence that the modulating effect of cortisol may involve cAMP.

Exogenous ACTH1-24 promotes adrenal maturation in fetal sheep, and this effect appears to be modulated in part by cortisol (Challis et al. 1985). We have examined whether similar changes in adrenal metabolism of progesterone occur with ACTH-induced labour as at spontaneous term and whether the site of cortisol modulation is on adrenal steroidogenesis or at the level of cAMP generation. Chronically catheterized fetal sheep were infused in utero for 100 h between days 127 and 131 of pregnancy with P-ACTH, P-ACTH + metopirone, P-ACTH + metopirone + cortisol, or saline. After 100 h the metabolism of [3H]progesterone was measured in adrenal homogenates. Similar incubations were performed with adrenal tissue from fetal sheep at day 130 of pregnancy and at spontaneous labour. In the treatment groups of sheep, cAMP output by dispersed adrenal cells in response to ACTH added in vitro was also determined. Similar qualitative patterns of [3H]progesterone metabolism were found in adrenal homogenates after in vivo ACTH or at term. At both times there was an increase in cortisol and in total 17 alpha-hydroxycorticosteroid accumulation and also evidence for increased activity of 11 beta-hydroxylase enzyme. The formation of total 17 alpha-hydroxycorticosteroids was not affected significantly by concurrent treatment in vivo with metopirone +/- cortisol. The accumulation of cAMP in vitro was increased after in vivo ACTH, attenuated after ACTH + metopirone, but statistical significance over controls was restored after ACTH + metopirone + cortisol treatment. We conclude that ACTH-induced labour and spontaneous parturition in sheep is associated with qualitatively similar changes in progesterone metabolism by the fetal adrenal gland.(ABSTRACT TRUNCATED AT 250 WORDS)

17-Hydroxycorticosteroids↗

PubMed1986

Effects of steroids on progesterone output by explants of human chorion.

Human chorion can synthesize and metabolize progesterone, and changes in progesterone synthesis by chorion at term might be important in the processes leading to parturition. We examined whether other steroids present within the maternal compartment and amniotic fluid during late pregnancy influence progesterone output by explants of chorion. We also sought differences in steroid effects on progesterone output in association with labor. Explants were prepared from chorion collected after the spontaneous onset of labor and vaginal delivery and chorion collected after cesarean section without active labor. To study the short-term effects of steroids on progesterone output by chorion, explants were incubated for 4 h with 3 microM pregnenolone and 3 microM of a potential interacting steroid. Other explants were preincubated for 24 h with steroid, then rinsed and incubated for 4 h with 3 microM pregnenolone and 3 microM of the same steroid as during preincubation. Under these conditions, dehydroepiandrosterone and androstenedione inhibited progesterone output by explants of chorion obtained at spontaneous labor and at cesarean section. Testosterone also inhibited progesterone output, but only in cesarean section chorion. If explants were preincubated for 24 h with steroid and then rinsed and incubated for 4 h with pregnenolone only, progesterone synthesis returned to control values. This finding indicates that the mechanism of action of these inhibitory steroids is likely through an effect on 3 beta-HSD activity and not due to a change in the rate of enzyme synthesis. We also noted apparent stimulatory effects of steroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

PubMed1986

Influence of 20 alpha-dihydroprogesterone on progesterone output by human chorion explants.

The output of progesterone by explants of chorion incubated without exogenous precursor was increased in the presence of 20 alpha-dihydroprogesterone (20 alpha-diHP). We have now examined the nature of the 20 alpha-diHP effect. Explants of chorion were incubated with [3H]progesterone and 3 microM non-radiolabelled 20 alpha-diHP to examine the effect of 20 alpha-diHP on progesterone metabolism. Significantly more radioactivity remained as unmetabolized [3H]progesterone compared to chorion incubated in the absence of non-radiolabelled 20 alpha-diHP. There was also a decrease in the output of [3H]-20 alpha-diHP by the explants but no change in the output of a second metabolite of progesterone [3H]-5 alpha-pregnanedione. When explants were incubated with 20 alpha-diHP in the presence of the 3 beta-hydroxysteroid dehydrogenase inhibitor, trilostane, the output of progesterone was significantly greater than with explants incubated with trilostane but without addition of 20 alpha-diHP. Radiochemically pure [3H]progesterone was produced by explants of chorion incubated with [3H]-20 alpha-diHP. We conclude that 20 alpha-diHP may serve as substrate for chorionic progesterone production through 20 alpha-hydroxysteroid dehydrogenase. 20 alpha-diHP, formed from progesterone, may also exert product feedback inhibition on this enzyme.

20-alpha-Dihydroprogesterone↗

PubMed1986

Prostaglandin concentrations in ovine maternal and fetal tissues at late gestation.

Maternal and fetal sheep organs were measured for their concentrations of prostaglandins (PG) E2, F2 alpha, 13,14-dihydro-15-keto PGF2 alpha (PGFM), 6-keto PGF1 alpha (hydrolysis produce of PGI2), and 6-keto PGE1 (enzymatic product of PGI2) by radioimmunoassay at day 131 of pregnancy (0.90 gestation). It was observed that the concentrations of PGFM were greater (p less than 0.01) in maternal endometrium than in any other maternal tissue or any other PG measured in endometrium. The lowest concentrations of PG in maternal tissues were in the myometrium, while PGE2 and 6-keto PGF1 alpha were present in maternal lungs in high concentrations. Fetal prostaglandin concentrations were high in the chorioallantois, fetal portion of the cotyledons and amnion, while they were very low in the kidney, liver, and lung. Fetal lung concentrations were lower than maternal lung concentrations (p less than 0.01) for all PG measured. In fetal aorta and ductus arteriosus, 6-keto PGF1 alpha concentrations were significantly greater (p less than 0.05) than all other measured PG, while in umbilical artery and vein 6-keto PGF1 alpha levels were equal to PGE2 levels. 6-Keto PGE1 concentrations were consistently among the lowest in all tissues measured. These results suggest that the endometrium may serve as a metabolic barrier to PG diffusing from the chorioallantois to the myometrium, that the capacity of pulmonary tissue to produce PG may increase with age, that the fetal membranes and cotyledons may be one major source of circulating PG in the fetus, and that 6-keto PGF1 alpha is the major metabolite of PGI2 in ovine tissues.

6-Ketoprostaglandin F1 alpha↗

PubMed1986

Androstenedione metabolism in the late gestation sheep fetus.

We have determined metabolic parameters for androstenedione (A) in chronically catheterized late gestation (day 130) sheep fetuses. The MCR (MCRA) was 3210 +/- 229 (SEM, n = 12) ml/min, the fetal arterial whole blood concentration of A [A] was 65 +/- 5 pg/ml, and the blood production rate (PRA) was 204 +/- 20 ng/min. Pulsatile administration of ACTH in amounts that raised fetal arterial plasma cortisol concentrations by 5- to 7-fold increased [A] to 154 +/- 20 pg/ml and PRA to 471 +/- 31 ng/min with no change in MCRA. In the presence of metopirone to block fetal adrenal cortisol output, ACTH treatment still provoked elevations in [A] (to 198 +/- 23 pg/ml) and PRA (539 +/- 158 ng/min), without altering MCRA. The major radiolabeled product in blood of infused [3H]A was [3H]testosterone; smaller amounts of phenolic steroids were formed. Extensive metabolism of [3H]A occurred in whole blood in vitro. The major product was [3H]testosterone; the 17-oxidoreductase activity was associated with the red blood cells. Umbilical vein [A] was greater than umbilical artery [A]; ACTH treatment increased [A] in both vessels. Concomitant metopirone abolished the arteriovenous difference by eliminating the ACTH-induced increase in venous [A], although arterial [A] rose significantly. The venous [A] and the arteriovenous gradient were restored with exogenous glucocorticoid treatment to the fetus. Collagenase-dispersed fetal adrenal cells secreted A. Adrenal cells from fetuses pretreated with ACTH in vivo had higher basal and ACTH-induced output of A in vitro than cells from fetuses pretreated with saline in vivo. We conclude that the MCRA in fetal sheep is extremely high, in part due to conversion of A to testosterone in fetal blood. The elevated PRA after ACTH plus metopirone and the lack of an umbilical arteriovenous gradient of [A] in this, but not other groups of fetuses, suggests a source of A production independent of the cortisol-induced changes in the placenta. Direct evidence is provided for fetal adrenal secretion of A which is enhanced by ACTH pretreatment of the fetus in vivo and for the utilization of circulating A in the fetus as a precursor for estrogen in both fetal and maternal compartments.

Adrenal Glands↗

PubMed1986

Parturition.

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Animals↗

PubMed1985

Propranolol inhibits the maturational effect of adrenocorticotropin in the fetal sheep lung.

We reported previously that metyrapone inhibited the maturational effect of adrenocorticotropin in the fetal sheep lung, even in the presence of exogenous glucocorticoids. To examine the role of beta-adrenergic input in this response we examined lung maturation in fetal sheep treated for 100 hours in vivo with adrenocorticotropin (66 ng/min for 15 minutes every 2 hours, n = 5); adrenocorticotropin plus propranolol (40 micrograms/min, n = 4), or saline solution (n = 8). Pulmonary maturation was assessed by pressure-volume curves, phospholipid content, and morphologic features. The basal cortisol level rose from less than 5 to 32.0 +/- 12.1 and 83.5 +/- 8.0 ng/ml in the adrenocorticotropin and adrenocorticotropin plus propranolol groups, respectively. The adrenal:body weight ratio (X 10(-4)) rose from 1.43 +/- 0.12 in the saline solution group to 2.90 +/- 0.16 and 2.51 +/- 0.14 in the adrenocorticotropin and adrenocorticotropin plus propranolol groups, respectively. Lung distensibility (milliliters of air per gram of lung) rose from 1.10 +/- 0.14 to 1.90 +/- 0.20 in the adrenocorticotropin group but was unchanged (0.98 +/- 0.24) in the adrenocorticotropin plus propranolol group. Phosphatidylcholine (milligrams per gram of lung) in the lung lavage rose from 0.07 +/- 0.02 to 0.23 +/- 0.11 in the adrenocorticotropin group but was not significantly changed (0.12 +/- 0.06) in the adrenocorticotropin plus propranolol group. We conclude that propranolol inhibits the maturational effects of adrenocorticotropin on the fetal lung, which implies that the mechanism of pulmonary maturation is not solely dependent on endogenous cortisol and must be mediated, at least in part, through adrenergic responses.

Adrenal Glands↗

PubMed1985

Relation between cyclic adenosine monophosphate and prostaglandin output by dispersed cells from human amnion and decidua.

We have examined the ability of activators of adenylate cyclase and cyclic adenosine monophosphate to affect the output of prostaglandins E and F by dispersed cells of amnion and decidua collected from women following spontaneous labor. Cyclic adenosine monophosphate production by amnion and decidua cells was stimulated in a dose-dependent fashion by cholera toxin and by forskolin in the absence or presence of the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine. Forskolin and cholera toxin also stimulated prostaglandin E and F output from amnion and decidua cells. Similar effects were seen with cells incubated with dibutyryl cyclic adenosine monophosphate +/- 3-isobutyl-1-methyl xanthine. The beta-adrenergic receptor agonists salbutamol, isoproterenol, and epinephrine all stimulated prostaglandin E and F output from dispersed cells of both tissues. The stimulatory effect of 3-isobutyl-1-methyl xanthine was partially additive with the Ca2+ ionophore A23187. Basal outputs of prostaglandin and outputs stimulated by A23187 and by N6, O2'-dibutyryl adenosine 3':5'-cyclic monophosphate were attenuated by the calmodulin antagonist trifluoperazine in a dose-dependent fashion. We conclude that mechanisms exist for stimulation of adenylate cyclase in human amnion and decidua resulting in enhanced prostaglandin output. This pathway requires basal interaction with Ca2+-calmodulin and may be additive with cyclic adenosine monophosphate-independent mechanisms for prostaglandin stimulation.

1-Methyl-3-isobutylxanthine↗

PubMed1985

Changes in the synthesis and metabolism of prostaglandins by human fetal membranes and decidua at labor.

The production of prostaglandins by dispersed cells from human amnion, chorion, and decidua was examined at term before the onset of labor and at spontaneous vaginal delivery. In order to obtain detailed information about relative prostaglandin production rates, the time course of prostaglandin output was examined by incubating the cells for up to 4 hours and measuring the cumulative output of prostaglandin E2, prostaglandin F2 alpha and 13,14-dihydro-15-keto-prostaglandin F2 alpha in the incubation media. The output of all three prostaglandins was low in tissues obtained before the onset of labor. At labor there was an increased production of prostaglandins E2 and F2 alpha in amnion and a small increase in the output of prostaglandin E2, prostaglandin F2 alpha, and 13,14-dihydro-15-keto-prostaglandin F2 alpha in decidua. In contrast, chorionic cells obtained at spontaneous vaginal delivery showed high levels of 13,14-dihydro-15-keto-prostaglandin F2 alpha in the media with no net production of prostaglandin E2 or F2 alpha. These data suggest a high rate of specific in vitro prostaglandin synthesis in amnion and decidua at labor, accompanied by a high rate of prostaglandin metabolism in chorion.

Amnion↗

PubMed1985

Changes in pituitary responses to synthetic ovine corticotrophin releasing factor in fetal sheep.

The rise in cortisol in fetal sheep during late pregnancy has been related to increased responsiveness of the adrenal to ACTH. Most reports have suggested that plasma ACTH concentrations rise coincident with or after the prepartum increase in cortisol. To reexamine the relationship of cortisol with basal immunoreactive ACTH (IR-ACTH) throughout the last 40 days of pregnancy and to determine changes in fetal pituitary responsiveness during this time, we measured basal and synthetic ovine corticotrophin-releasing factor (oCRF) (10 ng-10 micrograms) induced rises in ACTH and cortisol in fetal sheep at days 110-115, 125-130, and 135-140 of pregnancy. The fetuses were catheterized on day 105-120 and entered spontaneous labour at greater than 140 days. Basal IR-ACTH (picograms per millilitre +/- SEM) rose from 16.7 +/- 2.9 pg/mL at day 110-115 to 34.8 +/- 8.7 pg/mL at day 141-145. There was a significant effect of time on basal ACTH concentrations with a mean increase of approximately 5 pg ACTH per millilitre of plasma per 5-day sampling interval. Plasma cortisol changed gradually between day 110 and 125 of gestation and then more rapidly to term. At day 110-115 of gestation there was no significant change in plasma ACTH after 10 or 100 ng oCRF, but there was a significant increase in ACTH after 1 microgram of oCRF. Plasma cortisol did not change after any CRF injection. The change in IR-ACTH after oCRF at day 125-130 of gestation was significantly greater than that at day 110-115. Plasma cortisol concentrations were elevated following 1- and 10-micrograms injections of oCRF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1985

Prostanoid concentrations in maternal/fetal plasma and amniotic fluid and intrauterine tissue prostanoid output in relation to myometrial contractility during the onset of adrenocorticotropin-induced preterm labor in sheep.

Prostanoid [prostaglandin (PG)] concentrations were measured in ovine maternal and fetal plasma and amniotic fluid during the onset of preterm labor induced by the administration of a pulsatile infusion of ACTH-(1-24) (P-ACTH; 66.7 ng/min for 15 min every 2 h) to the fetus and in saline-infused controls. P-ACTH administration stimulated a change in intra-uterine pressure from type A-activity, characterized by sustained increases of low amplitude, to type B labor-like activity of short duration, high amplitude (greater than or equal to 10 mm Hg) increases which occurred between 12 and 8 h before the onset of labor. PGF2 alpha and/or PGFM (13,14-dihydro-15-keto PGF2 alpha) concentrations increased consistently in all fluids 16 h or earlier before labor. All PGs increased in fetal carotid arterial plasma (PGE2 greater than PGF2 alpha) and amniotic fluid, and the relative increases in each PG were similar. However, PGF2 alpha and PGFM selectively increased in maternal vena caval and aortic plasma, whereas smaller or negligible increases in the prostacyclin hydrolysis metabolite 6-keto PGF1 alpha (6KF) and PGE2 were noted. The output of PGs E2 and F2 alpha (picograms per 10(5) cells/8 h) increased 1.6- and 1.7-fold, respectively, by cells dispersed from the chorioallantois of P-ACTH-treated animals compared to that in control animals infused with saline for 100 h. From fetal cotyledons, these increases were 2.4-fold (P less than 0.05) and 3.6-fold, respectively. No significant changes occurred in 6-keto PGF1 alpha output from any tissue or PGE2 or PGF2 alpha output from amnion or maternal cotyledons. We conclude 1) that PGs increase in all fluids before the increase in uterine mechanical activity during induced preterm labor, implying that PGs mediate this event and are not a result thereof; 2) that syntheses of PGs E2 and F2 alpha increase similarly in intrauterine tissues with the onset of labor; and 3) that a selective increase in PGF2 alpha, a myometrial stimulatory PG, occurs exclusively in maternal plasma, suggesting that endoperoxide conversion to PGF2 alpha is specifically enhanced during parturition or suggesting the existence of an intrauterine tissue source of 9-keto PG reductase.

6-Ketoprostaglandin F1 alpha↗

PubMed1985

Possible role of cortisol in the stimulation of cortisol-binding capacity in the plasma of fetal sheep.

In sheep, the prepartum rise in fetal plasma cortisol (F) is associated with an increase in the corticosteroid-binding capacity (CBC) of the plasma. We examined whether CBC changed during preterm labor, induced by administering ACTH to the fetus, and we examined the role of F in such changes. Beginning on day 127, chronically catheterized fetal sheep were divided into six groups; 1) saline control infusions (n = 4); 2) pulsatile ACTH (P-ACTH; 66 ng/min for 15 min every 2 h; n = 5); 3) P-ACTH (as 2) plus metopirone (MET; 500 mg/24 h n = 5); 4) P-ACTH and MET (as 3) plus F (13.3 micrograms/min for 15 min every 2 h; n = 3); 5) P-ACTH and MET (as 3) plus F (133 micrograms/min for 15 min every 2 h; n = 4); 6) P-ACTH and MET (as 3) plus dexamethasone (0.56 micrograms/min for 15 min every 2 h for 50 h, then 5.6 micrograms/min for 15 min every 2 h until 100 h; n = 4). All infusions continued for 100 h. Fetal blood samples were collected at 8-h intervals for determination of plasma F concentration and CBC. Estrone and progesterone were measured in 8-h samples of maternal femoral arterial blood. P-ACTH resulted in a significant increase in CBC within 24 h; values at 72-96 h were 2- to 3-fold greater than controls. Rises in CBC were positively correlated with the changes in plasma F in the P-ACTH-treated fetuses and preceded changes in plasma progesterone or estrogens. MET treatment prevented the P-ACTH-induced increases in F and CBC. Exogenous F and dexamethasone overcame the MET-induced inhibition of P-ACTH-induced increases in CBC. We conclude that in fetal sheep 1) CBC is elevated by P-ACTH treatment; and 2) F may mediate this stimulation of its own binding protein.

Adrenocorticotropic Hormone↗

PubMed1985

Modulation by cortisol of adrenocorticotropin-induced activation of adrenal function in fetal sheep.

We examined the hypothesis that cortisol (F) modulates the activation of adrenal function induced by treating fetal sheep in vivo with pulsatile ACTH (P-ACTH). Chronically catheterized sheep fetuses were infused in utero for 100 h between day 127 and day 131 of pregnancy with P-ACTH; P-ACTH plus metopirone; P-ACTH plus metopirone plus F; P-ACTH plus metopirone plus dexamethasone, or saline (controls). After 100 h, basal and ACTH-stimulated output of 11-desoxycortisol (S), F, and progesterone from collagenase-dispersed fetal adrenal cells was measured. Adrenal cells from fetuses treated with P-ACTH in vivo had significantly greater basal and stimulated (delta) outputs of F and S in vitro than controls. These effects were attenuated in fetuses pretreated with P-ACTH plus metopirone. Concurrent in vivo treatment with ACTH plus metopirone plus F restored basal and delta outputs of F and S to values that were not significantly different from those after P-ACTH alone. In vivo treatment with dexamethasone in addition to P-ACTH plus metopirone significantly raised basal outputs of F and S, but the cells were unresponsive to ACTH in vitro. Basal output of progesterone was significantly greater after in vivo P-ACTH plus metopirone plus dexamethasone, but no treatment raised delta progesterone output over controls. These results support a role for glucocorticoids in modulating ACTH-induced activation of adrenal function in late gestation fetal sheep.

Adrenal Glands↗