Biomedical subjects

J R Challis

Publications and source records attributed to J R Challis.

At least 163 records · Page 9Linked to original sources

PubMed1988

The effects of pulsed adrenocorticotropin1-24 administration to one twin on the endocrine and uterine activity changes during twin pregnancy in sheep.

To test the hypothesis that systemic endocrine events are of more importance than local intrauterine endocrine changes in the control of myometrial activity at labor, we examined the endocrine changes and development of uterine activity in chronically catheterized twin fetal sheep during administration of adrenocorticotropin1-24 (ACTH1-24) to one of the twins. Fetal and maternal plasma cortisol, progesterone, estrone, prostaglandin E2 (PGE2) and 13, 14 dihydro 15-keto prostaglandin F2 alpha (PGFM) were measured before and during pulsatile administration of ACTH1-24 (1 microgram infused over 15 min, every 2 h; P-ACTH) to one fetus in each of six twin pregnancies until parturition was initiated. In all cases, each fetus was in a separate uterine horn. The same hormone measurements were made in each co-twin that remained untreated. Intrauterine pressure and electromyographic activity of each uterine horn were monitored continuously throughout the study. In ewes pregnant with twins, the onset of active labor occurred after a mean infusion interval of 204.0 +/- 29.5 h (SEM), which is considerably longer than has been reported for singleton pregnancies. In the P-ACTH-infused twin, birth was preceded by a progressive rise in plasma cortisol beginning 24 h after the start of infusion. This was followed by a later rise in plasma estrone and PGE2, and by a decline in plasma progesterone. In the uninfused twin, delivery was preceded by a small rise in plasma cortisol that was concomitant with a rise in the concentration of cortisol in the maternal circulation. The concentrations of estrone and progesterone in the uninfused twin did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

The effect of gastrin-releasing peptide on the endocrine pancreas.

Infusion of GRP into conscious sheep and dogs produced elevations of systemic plasma levels of insulin, glucagon, and pancreatic polypeptide (PP). In the dog, infusions of GRP produced dose-dependent decreases in plasma glucose levels, whereas, in the sheep, dose-dependent increases in plasma glucose levels occurred. Glucose turnover studies demonstrated that infusions of GRP produce prompt increases in the rate of appearance of glucose in sheep, but previous studies demonstrated a transient decrease in the rate of appearance of glucose in dogs, suggesting that sheep and dogs differ in hepatic responses to the elevated levels of insulin and glucagon. GRP was a potent PP secretagogue in the sheep, whereas, in contrast to results in the dog, infusions of GRP did not result in elevations of plasma levels of gastrin in sheep. GRP has multiple complex stimulatory effects on the endocrine pancreas, and there exist species-dependent differences in responses, which affect the potency and spectrum of the hormone-releasing activity of GRP. Further studies are required to determine the precise anatomical relation of GRP-containing nerve fibers to islet cells and to elucidate the pathways by which GRP activates endocrine pancreatic hormone release.

Animals↗

PubMed1988

Regulation of the hypothalamic-pituitary-adrenal axis in birth.

In sheep an increase in fetal pituitary-adrenal function, reflected in rising concentrations of plasma ACTH and cortisol, is important in relation to fetal organ maturation and the onset of parturition. This review presents evidence that implicates the hypothalamic-pituitary-adrenal axis in the control of parturition and describes recent experiments that explore in detail the maturation of the fetal hypothalamus and pituitary in relation to fetal adrenal function. Recent improvements for the measurement of ACTH in unextracted plasma and the ability to maintain vascular catheters in chronically catheterized fetal sheep have enabled subtle changes in fetal ACTH concentrations to be detected. As a result of these advances it has now been established that the terminal rise in cortisol, which is responsible for the onset of parturition in sheep, is preceded by an increase in fetal plasma ACTH concentrations. This has led to the hypothesis that birth results from the sequential development of the fetal hypothalamic-pituitary-adrenal axis with the signal originating from the fetal brain. This increase in trophic drive to the fetal adrenal may result from changes in the responsiveness of the fetal pituitary gland to factors that stimulate the release of ACTH. Corticotropin releasing factor (CRF) and arginine vasopressin are two such factors that stimulate the secretion of ACTH and cortisol secretion in the chronically catheterized fetal sheep. The response to these factors increases with gestational age and is sensitive to glucocorticoid feedback. Furthermore, repeated administration of CRF to immature fetal sheep results in pituitary and adrenal activation and in some cases may lead to premature parturition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1988

Ovine fetal urachus--physiological and hormonal control of its contractile activity.

We have investigated whether the ovine fetal urachus near term has the potential to regulate the passage of urine from the bladder into the allantoic cavity. Experiments were performed primarily on longitudinal urachal muscle. In Krebs bicarbonate buffer (pH 7.4 bubbled with 95% O2-5% CO2 at 37 degrees C) the urachus spontaneously developed a prolonged elevated resting tension (RT, 1.1-1.5 g). Intra-abdominal urachus showed a greater development of tension than extra-abdominal urachus, which was associated with the amount of smooth muscle observed in histological specimens. Isoproterenol (1 microM) produced a significant reversible reduction in RT (1.36 +/- 0.15 to 0.67 +/- 0.08 g, P less than 0.01, mean +/- SE). Replacement of normal-O2 buffer (PO2 420.4 +/- 19.5 mmHg) with a low-O2 buffer (PO2 101.3 +/- 4.7 mmHg), or very low-O2 buffer (PO2 38.2 +/- 2.2 mmHg) while maintaining PCO2 and pH constant, produced a reduction in RT (from 1.35 +/- 0.21 to 0.52 +/- 0.13 g and from 1.20 +/- 0.17 to 0.46 +/- 0.04 g, respectively; both P less than 0.01). This effect was reversed when high PO2 was reinstated. Circular muscle showed a similar response when PO2 was reduced. The urachus showed a significant increase in RT (0.74 +/- 0.08 to 1.71 +/- 0.28 g, P less than 0.01) when prostaglandin F2 alpha (PGF2 alpha; 10 microM) was added to the low-O2 buffer. These results demonstrate that the urachus can develop spontaneous contractile activity and responds to alterations in O2, a beta-agonist, and PGF2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Exogenous opioid regulation of the hypothalamic-pituitary-adrenal axis in fetal sheep.

To test the hypothesis that endogenous opioids participate in the regulation of the ontogenic development of the hypothalamic-pituitary-adrenal axis in fetal sheep, we measured changes in immunoreactive (ir) ACTH and cortisol concentrations in response to bolus injections of either the [Met]-enkephalin analogue, [D-Ala2,N-Phe4,Met(0)ol5]-enkephalin (FK 33-824; 25 micrograms), the opioid antagonist naloxone (1 mg), a combination of both, or saline vehicle, administered to chronically catheterized fetal sheep through late gestation. There were no effects of either FK 33-824, naloxone or saline on the release of ir-ACTH and cortisol at the earliest stage of gestation studied (days 110-115). By days 125-130, FK 33-824 caused a rapid but short-lived (30 min) increase in plasma ir-ACTH (P less than 0.05) which was accompanied by a smaller but nonsignificant increase in cortisol. Naloxone given concurrently with FK 33-824 abolished this response, thus providing evidence for a specific effect through opioid receptors. Naloxone given alone was without effect. At days 135-140, FK 33-824 caused a significant increase in ir-ACTH which was of similar duration and magnitude to that which occurred at days 125-130. There was a larger basal variation in plasma concentrations of cortisol than at days, 125-130, and a greater increase in cortisol after FK 33-824, although this did not reach statistical significance. Naloxone again reversed the effects of FK 33-824 but was without effect when given alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1988

Insulin-like growth factor (IGF)-II and insulin, but not IGF-I, are mitogenic for fetal rat adrenal cells in vitro.

The agents controlling growth of the fetal adrenal gland are poorly defined. The purpose of the present study was to determine the factors required to promote proliferation of adrenal cells obtained from fetal rats at 20 days of gestation and grown in monolayer cell culture under serum-free conditions. Insulin stimulated [3H] thymidine incorporation into DNA at all concentrations (0.01-10 mg/l) tested. Rat insulin-like growth factor (IGF)-II in the presence of insulin promoted a dose-dependent increase in mitogenic activity, with a half-maximal concentration of approximately 1 microgram/l; IGF-II had no effect in the absence of insulin. There was no significant effect of IGF-I on mitogenic activity in the presence or absence of insulin. Adrenal cell DNA synthesis was not stimulated by ACTH, several ACTH-related peptides, a variety of known growth factors, several steroids, or conditioned medium from fetal adrenal cells. We conclude that in the presence of insulin, IGF-II is a specific growth factor for the fetal rat adrenal. We also suggest that rat fetal adrenal cells, in common with other epithelial cell types under serum-free culture conditions, may respond to this progression factor without an obligatory requirement for an initial exposure to competence factors.

Adrenal Glands↗

PubMed1988

Urethral and urachal urine output to the amniotic and allantoic sacs in fetal sheep.

A chronic fetal sheep preparation was developed to measure, without interruption in utero, urethral and urachal urine output to the amniotic and allantoic sacs, respectively. Fetal urethral, urachal and total urine output was measured during a 5 day post-operative period, in late gestation. Total fetal urine output increased from day 1 to a volume of 1216 +/- 115 ml/day (SEM) on day 5 post-operative. Urachal urine output increased significantly from 12 ml/day on day 1 to 467 ml/day on day 5 (P less than 0.05). Fetal arterial blood gases, pH and immunoreactive ACTH, cortisol and immunoreactive arginine vasopressin concentrations were stable throughout the 5-day recovery period. Fetal urachal urine output to the allantoic cavity and total fetal urine output appears to require 4-5 days to stabilize post-operatively. Fetal urine is a major source of amniotic and allantoic fluid in late gestation and the volume of these sacs may be influenced, in part, by the distribution of urethral and urachal urine output.

Adrenocorticotropic Hormone↗

PubMed1988

Basal serum-free culture system which supports growth of fetal rat adrenal cells in primary monolayer cell culture.

A serum-free culture system has been developed which allows primary cultures of fetal rat adrenal cells to divide in response to insulin 10 micrograms/l, yet retain their ability to respond to adrenocorticotropic hormone (ACTH) by increased corticosterone production. The essential components of this culture system are: (1) a high initial plating number of 125-130 x 10(3) cells/cm2; (2) a low oxygen concentration of 2.5% O2; (3) an initial plating period of 48 h in greater than or equal to 5% (v/v) fetal bovine serum. In contrast to reported requirements for the serum-free growth of adult adrenal cells, the fetal adrenal cells do not require the provision of any special matrix or a competence factor for serum-free growth or steroidogenic activity. This suggests that they are capable of rapidly generating their own matrix and competence factor in primary culture.

Adrenal Glands↗

PubMed1987

Progesterone synthesis by human amnion, chorion, and decidua at term.

We investigated the ability of human fetal membranes to produce progesterone from a variety of substrates. Chorion is more active than decidua, and amnion produces little progesterone. Cholesterol or low-density lipoprotein cholesterol was not used as a substrate. Chorion used pregnenolone, pregnenolone sulfate, and 20 alpha-dihydroprogesterone for progesterone synthesis. Decidua also used these three substrates but produced significantly less progesterone than chorion. Amnion used only 20 alpha-dihydroprogesterone as a substrate. Exogenous human chorionic gonadotropin or gonadotropin-releasing hormone or its analogues did not influence progesterone production by any of the tissues. There were several significant changes in substrate usage for progesterone synthesis by the tissues around the time of the onset of labor. Tissue concentrations of progesterone are approximately 4 ng/mg protein, and it appears that local production rates could completely account for this. These data are compatible with the hypothesis that local regulatory mechanisms may determine progesterone concentrations in fetal membrane tissues and that important changes may occur around the time of the onset of parturition.

20-alpha-Dihydroprogesterone↗

PubMed1987

Steroid synthetic and prostaglandin metabolizing activity is present in different cell populations from human fetal membranes and decidua.

We examined whether different cell subpopulations from human fetal membranes and decidua produce steroids (estrone and progesterone) and metabolize prostaglandins (prostaglandin F2 alpha to 13, 14-dihydro-15-keto-prostaglandin F2 alpha and if these changed with labor. Amnion, chorion, and decidua were obtained at elective cesarean section at term or at spontaneous labor. Cells were dispersed with collagenase and separated by density on discontinuous Percoll gradients. At cesarean section there was a major broad band of cells from amnion and chorion. This band contained most of the estrone sulfatase (estrone sulfate to estrone) activity. The 3 beta-hydroxysteroid dehydrogenase (pregnenolone to progesterone conversion) and prostaglandin F2 alpha metabolizing activities were present in these cells and those that migrated at greater Percoll densities. Amnion and chorion obtained after spontaneous labor had two major bands of cells. Estrone sulfatase was present in cells from both hands, whereas progesterone output from pregnenolone and prostaglandin F2 alpha metabolism predominated in the second band of cells with greater density. This pattern was particularly apparent in chorion. Dispersed cells from decidua tended to migrate throughout the gradient. In general, estrone sulfate to estrone conversion predominated in lighter cells whereas progesterone output from pregnenolone and prostaglandin F2 alpha metabolism predominated in cells of greater density. The output of progesterone from pregnenolone was significantly lower in cell preparations from chorion and decidua at spontaneous labor compared with cesarean section. We conclude that human amnion, chorion, and decidua contain distinct cell subpopulations based on Percoll migration and that in the membranes these change between cesarean section and spontaneous labor. Partial separation of estrone sulfatase from 3 beta-hydroxysteroid dehydrogenase and prostaglandin F2 alpha metabolizing activities has been demonstrated, which raises the possibility of paracrine interactions in vivo.

Cells, Cultured↗

PubMed1987

Estrogen, progesterone, prolactin, prostaglandin E2, prostaglandin F2 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha, and 6-keto-prostaglandin F1 alpha gradients across the uterus in women in labor and not in labor.

Before or during labor in humans, changes in peripheral levels of estrogen and progesterone are not evident. Local alterations of estrogen, progesterone, and prolactin concentrations may be present and be accompanied by prostaglandin changes. The purpose of this study was to investigate the differences in concentrations of these hormones across the uterus and to evaluate their interrelationships in patients at term gestation with and without labor. Blood samples were obtained from a radial artery and a uterine vein in 22 women without and in 10 with labor. The difference between levels in the two blood vessels was designated as the gradient. Neither levels nor gradients were different between the two groups for estrone, estradiol, estriol, progesterone, or prolactin. The plasma levels of prostaglandin F2 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha, and prostaglandin E2 were significantly increased in labor. Prostacyclin levels, as indicated by the 6-keto-prostaglandin F1 alpha metabolite, were not altered. The gradients for prostaglandin F2 alpha and E2 were significantly increased in labor. The results of the study also suggested that, in gestation at term, serum prolactin is produced mainly by the pituitary and that estrone may originate from peripheral conversion of estradiol. We conclude that in humans prostaglandin gradients of the E and F groups are increased in labor. These increases are not associated with changes in sex steroids or prolactin. Prostacyclin metabolite gradients also appear not to be altered in labor, suggesting that some prostaglandins are selectively increased in early labor either by enhanced production or decreased metabolism or both.

6-Ketoprostaglandin F1 alpha↗

PubMed1987

Tissue-specific concentration changes of estrone and estradiol during spontaneous and ACTH-induced parturition in sheep.

Changes in estrogen production are considered important in the sequence of events leading to parturition. We sought tissue-specific changes in the concentration of unconjugated estrone (E1) and estradiol (E2) in intrauterine fetal (amnion, chorion) and maternal (endometrium, myometrium) tissues during normal pregnancy, labour, and ACTH-induced labour in sheep. The mean concentrations of E1 and E2 in the fetal membranes were higher than in endometrium and myometrium. In amnion there were no consistent changes in estrone concentrations with gestation, although estradiol concentrations increased between day 130 and term. In the endometrium there were increases in both estrone and estradiol between day 100 and term, whereas in the myometrium increases in the concentrations of E1 and E2 occurred between days 130-135 and term. Animals showing a labourlike pattern of uterine contractions after intrafetal ACTH administration did not show significant differences in estrone or estradiol concentrations in amnion, chorion, or endometrium compared with saline-infused controls. However, there was a progressive increase in the concentration of estrone and estradiol in the myometrium during ACTH-induced labour. We conclude that changes in the concentrations of estrone and estradiol in intrauterine tissues vary between the tissues studied and the two estrogens. In general, estrogen concentrations increased towards term, but this trend was more marked in the maternal than fetal tissues. The changes in estrone concentrations in myometrium, but not in the other tissues, were replicated during ACTH-induced labour. Our results would be compatible with the suggestion that tissue-specific changes in estrogen concentrations may contribute to the local intrauterine steroid milieu during pregnancy and at term.

Adrenocorticotropic Hormone↗

PubMed1987

The effects of gestational age and intrafetal ACTH administration on the concentration of progesterone in the fetal membranes, endometrium, and myometrium of pregnant sheep.

To examine the hypothesis that progesterone withdrawal from intrauterine tissues is a prerequisite to spontaneous labour or labour induced by administering ACTH to the ovine fetus, we measured the concentration of progesterone in amnion, chorion, endometrium, and myometrium of sheep at different stages of pregnancy and during ACTH-induced labour. There was no significant change in the concentration of progesterone nor in the progesterone:estradiol ratio in amnion or chorion in association with either spontaneous or ACTH-induced labour. The concentration of progesterone in endometrium rose significantly between days 50-60 and days 130-135 of gestation and decreased at term. There was also a fall in the progesterone:estradiol ratio in endometrium between days 130-135 and term. Neither the progesterone concentration not the progesterone:estradiol ratio changed in endometrium during ACTH-induced labour. In the myometrium the concentration of progesterone rose significantly between days 50-60 and day 100 of pregnancy and decreased between day 100 and days 130-135, with a further decline towards term. After intrafetal ACTH there was no change in the concentration of progesterone in the myometrium, although there was a fall in the progesterone:estradiol ratio. We conclude that labour occurring spontaneously at term is associated with a decrease in the progesterone concentration of maternal intrauterine tissues, the myometrium and endometrium. In contrast, there is no decline in the progesterone concentrations of the fetal membranes, the amnion and chorion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1987

Dexamethasone inhibits ovine corticotrophin-releasing factor (oCRF), arginine vasopressin (AVP), and oCRF + AVP stimulated release of ACTH during the last third of pregnancy in the sheep fetus.

We examined the hypothesis that in fetal sheep during late pregnancy exogenous glucocorticoids might affect differentially the pituitary response, measured as changes in plasma ACTH concentrations, to the systemic administration of ovine corticotrophin-releasing factor (oCRF), arginine vasopressin (AVP), or oCRF + AVP. At d 113-116 of pregnancy, equimolar injections of oCRF and AVP given separately provoked similar significant increases in plasma ACTH; the change in ACTH over basal values was significantly greater than the sum of the two separate responses when AVP + oCRF were given together. Exogenous dexamethasone did not affect basal ACTH concentrations, but suppressed significantly the responses to oCRF, AVP, and oCRF + AVP. At d 126-130, there was a significant ACTH response to CRF alone and to AVP + oCRF, but not to AVP alone. The response during the first 30 min postinjection to oCRF was significantly less than that to AVP + oCRF. Plasma cortisol rose after each peptide injection. Exogenous dexamethasone suppressed both basal and stimulated responses to each peptide. At the amounts injected, there was no significant ACTH or cortisol response to oCRF, AVP, or oCRF + AVP at d 136-140, but dexamethasone suppressed basal ACTH and cortisol concentrations at this time. We conclude that stimulated, but not basal, release of ACTH is subject to the negative feedback effect of exogenous glucocorticoid by d 113-116 of gestation in fetal sheep. Both basal and stimulated release of ACTH and cortisol are suppressed after d 125. At the amount of exogenous dexamethasone given, oCRF, AVP, and oCRF + AVP-stimulated responses are affected similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1987

Dose-dependent effects of arginine vasopressin on endocrine and blood gas responses of fetal sheep during the last third of pregnancy.

Arginine vasopressin (AVP) is released in fetal sheep in response to various intrauterine stresses such as hypoxaemia, hypotension, and haemorrhage. We have examined the effects of exogenous AVP injected at two doses (200 ng and 2 micrograms) on the plasma concentrations of ACTH and cortisol, and on arterial blood PO2, PCO2, and pH in chronically catheterized fetal sheep at d110-115, d125-130, and at d135-140 of pregnancy. AVP (2 micrograms) provoked a significant elevation in the plasma ACTH and cortisol concentration at all three stages of gestation, whereas the administration of 200 ng AVP raised plasma ACTH and cortisol only at d110-115 and at d125-130. The increment in plasma cortisol after 200 ng AVP at the two earlier stages of pregnancy was similar to that after 2 micrograms AVP, despite a dose-dependent difference in the change in ACTH concentration. AVP stimulated a rise in PaO2 at each time of study, although the time course of response was shorter at d135-140 than at the previous stages of pregnancy. The effect of AVP on PaCO2 was more variable, showing a transient decrease at +5 min after injection in the two oldest groups of fetuses. pH fell after AVP at d110-115 and at d125-130, but it rose transiently in the oldest fetuses. We conclude that at high concentrations systemic administration of AVP provokes endocrine and blood gas changes in fetal sheep. ACTH was consistently elevated by AVP. PaO2 also rose at each stage of pregnancy, but the effects on PaCO2 and pH varied as a function of fetal age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1987

Synergism between systemic corticotropin-releasing factor and arginine vasopressin on adrenocorticotropin release in vivo varies as a function of gestational age in the ovine fetus.

In sheep, parturition is associated with maturation of fetal pituitary-adrenal function, and with rises in the concentrations of ACTH and cortisol (F) in fetal plasma. We examined the hypothesis that pituitary ACTH output in response to arginine vasopressin (AVP) and CRF separately and together might change during late pregnancy as a function of fetal age. Fetal sheep were chronically catheterized, and bolus iv injections of equimolar AVP, CRF, AVP plus CRF, or saline (controls) were given on days 110-115, 125-130, and 135-140 of gestation. AVP evoked significant rises in plasma ACTH on days 110-115 and 125-130, but not on days 135-140. After AVP, the peak plasma concentrations of ACTH were attained at 5-10 min, and basal (preinjection) values were reestablished by 30-60 min. After CRF treatment, plasma ACTH rose progressively throughout the 240 min of the study. Evidence was obtained in support of an increase in pituitary responsiveness to CRF between days 110-115 and 125-130 and a decrease in response on days 135-140, when basal F concentrations were higher. The ACTH response to AVP, relative to that to CRF, was greatest in the youngest fetuses. On days 110-115 only, CRF and AVP showed a synergistic response in ACTH output, especially during the first 30 min after agonist injection. Plasma F rose in response to the changes in endogenously released ACTH in a manner consistent with progressive fetal adrenal maturation between days 110-140 of pregnancy. We conclude that in vivo the ovine fetal pituitary responds separately and synergistically to AVP and CRF on days 110-115 of gestation, but the relative role of AVP in stimulating ACTH release decreases with progressive gestational age.

Adrenocorticotropic Hormone↗

PubMed1987

Pituitary and adrenal responses to pulsatile ovine corticotropin-releasing factor administered to fetal sheep.

In fetal sheep a bolus injection of ovine CRF (oCRF) elevates plasma immunoreactive ACTH (IR-ACTH) during the last 5 weeks of gestation. However, the effects of long term administration of oCRF to fetal sheep have not been studied. We examined the effects of pulsatile administration of oCRF (1 microgram every 4 h) for 7 days on fetal pituitary and adrenal responses, as reflected by plasma concentrations of IR-ACTH and cortisol (F). In addition, we examined the effects of oCRF on cAMP accumulation by dispersed pituitary cells in vitro after treatment in vivo with either oCRF or saline. Pulsed oCRF (P-CRF) treatment resulted in a significant (P less than 0.05) increase in basal IR-ACTH and F concentrations on all days of treatment. However, the pituitary response (change in IR-ACTH in response to a pulse of oCRF) decreased, and the adrenal response (change in F in response to endogenously secreted ACTH) increased as treatment progressed. A significant inverse correlation (r = 0.962) between basal F and the IR-ACTH response to oCRF was seen over the 7 days of treatment. Although P-CRF treatment resulted in an increase in fetal adrenal weight, it did not lead to premature parturition. There was a dose-dependent accumulation of cAMP in response to oCRF in vitro by dispersed pituitary cells from both groups of fetuses. However, this response was significantly greater when the fetuses had been pretreated with oCRF in vivo than after saline treatment. We conclude that the P-CRF regimen employed in this study stimulates the fetal pituitary-adrenal axis and the ability of fetal pituitary cells to accumulate cAMP in response to further oCRF in vitro. The reduced plasma IR-ACTH response after continued P-CRF in vivo may be attributed to increasing negative feedback effects of elevated endogenous F.

Adrenal Glands↗

PubMed1987

Steroid production by dispersed cells from fetal membranes and intrauterine tissues of sheep.

The hypothesis was examined that the fetal membranes and the endometrium and myometrium of pregnant sheep have the ability to produce oestrogens and progesterone from exogenous precursors, and that this capacity might change during the course of pregnancy, and in relation to the onset of parturition. Cells were dispersed from samples of myometrium, endometrium, allantois, chorion and amnion from sheep at Day 50, Days 130-135 of pregnancy, and at term, in labour, and were incubated in the presence of pregnenolone and 20 alpha-dihydroprogesterone as potential precursors for progesterone production, and oestrone sulphate and androstenedione as potential precursors for oestrogen production. In addition, the metabolism of radioactive progesterone and oestrone sulphate by the dispersed cells was examined. Pregnenolone was converted to progesterone in significant amounts by dispersed cells from chorion and endometrium only. At Day 130 and at term this conversion was blocked by the addition of trilostane, an inhibitor of 3 beta-hydroxysteroid dehydrogenase activity. There was no significant change in the net production of progesterone from exogenous pregnenolone with gestation. 20 alpha-Dihydroprogesterone was converted to progesterone by all tissues, and at each stage of gestation. Formation of progesterone from 20 alpha-dihydroprogesterone was invariably greater than that from pregnenolone, but did not change with pregnancy. Oestrone sulphate was converted to oestrone and oestradiol by all tissues. In the myometrium and chorion this conversion was lower at term than at Day 50 of pregnancy. In contrast, there was very little conversion of androstenedione to unconjugated oestrogen, minimal activity being demonstrable only in dispersed cells from the chorion in some preparations. Radioactive progesterone was converted to radiochemically pure 17 alpha-hydroxyprogesterone by chorion, and to radiochemically pure 20 alpha-dihydroprogesterone by amnion, chorion, allantois and endometrium obtained at term pregnancy. At term [3H]oestrone sulphate was converted to radiochemically pure oestrone by all tissues. We conclude that there is a tissue-specific distribution of different steroid metabolizing enzyme activities in the fetal membranes and intrauterine tissues of pregnant sheep. Of the substrates examined, 20 alpha-dihydroprogesterone and oestrone sulphate were preferred for progesterone and oestrogen production, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗