Absence of fast negative feedback control of ACTH and renin in fetal and adult sheep

1986 ◽  
Vol 250 (3) ◽  
pp. R403-R410 ◽  
Author(s):  
C. E. Wood
Keyword(s):  
Negative Feedback ◽  
Feedback Inhibition ◽  
Plasma Renin ◽  
Renin Secretion ◽  
Fetal Sheep ◽  
Adult Sheep ◽  
Fetal Plasma ◽  
Negative Feedback Control ◽  
Time Courses ◽  
Vasodilator Drug

Fetal adrenocorticotropin (ACTH) and renin secretion are increased by a variety of stimuli and decreased by cortisol negative feedback inhibition. However, the time courses of these interactions are unknown. The present studies were designed to test for rapid feedback negative suppression of ACTH and renin secretion in fetal and adult sheep. In chronically catheterized fetal sheep, ACTH and renin secretion were stimulated by intravenous infusion of sodium nitroprusside, a vasodilator drug. Vehicle or cortisol, infused at rates of 1, 2, or 4 micrograms/min for 2 min before and during the infusion of nitroprusside did not significantly alter the fetal ACTH or renin responses to nitroprusside. In five nonpregnant ewes, chronically prepared with skin loops containing the carotid arteries, nitroprusside (20 micrograms X kg-1 X min-1) was infused beginning 2 min after infusion of vehicle or cortisol (3.5 or 7 micrograms X kg-1 X min-1). Cortisol infusion produced a rising plasma cortisol concentration similar to that after stress but did not alter the magnitude of the ACTH response to nitroprusside. The results indicate that cortisol-induced suppression of ACTH secretion does not occur rapidly in the fetal or adult sheep and that the cortisol-induced suppression of fetal plasma renin activity is a slow process.

Are fetal adrenocorticotropic hormone and renin secretion suppressed by maternal cortisol secretion?

1988 ◽  
Vol 255 (3) ◽  
pp. R412-R417 ◽  
Author(s):  
C. E. Wood
Keyword(s):  
Plasma Cortisol ◽  
Adrenocorticotropic Hormone ◽  
Plasma Concentrations ◽  
Plasma Renin ◽  
Maternal Plasma ◽  
Renin Secretion ◽  
Plasma Acth ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Adrenal Secretion

Previous studies from this laboratory have demonstrated that intravenous infusions of hydrocortisone (cortisol) into fetal sheep at rates that produce plasma concentrations achieved during fetal stress inhibit fetal adrenocorticotropic hormone (ACTH) and renin secretion. The present study was designed to test for inhibition of fetal renin and ACTH after maternal adrenal secretion of cortisol. ACTH-(1-24) or saline infusion into 12 pregnant ewes (120-132 days gestation) at rates of 0, 1, 5, or 20 ng ACTH.kg-1.min-1 for 5 h produced dose-related increases in maternal plasma ACTH and cortisol concentrations and fetal plasma cortisol concentration. In the 20-ng.kg-1.min-1 group, increases in fetal plasma cortisol of 8.0 ng/ml (to 24.3 +/- 3.7 ng/ml) did not suppress basal fetal plasma renin activity. One hour after the end of the maternal vehicle or ACTH infusion, fetal ACTH secretion was stimulated by fetal intravenous infusion of sodium nitroprusside. In the 0-, 1-, and 5-ng.kg-1.min-1 groups, fetal ACTH responses to nitroprusside were suppressed in animals infused with ACTH. Together, these results indicate that the maternal adrenal secretion of cortisol inhibits stimulated secretion of ACTH but not renin in 120- to 132-day-gestation fetal sheep.

Cortisol inhibits ACTH secretion in late-gestation fetal sheep

1991 ◽  
Vol 260 (2) ◽  
pp. R385-R388 ◽  
Author(s):  
C. E. Wood
Keyword(s):  
Negative Feedback ◽  
Plasma Cortisol ◽  
Sodium Succinate ◽  
Plasma Concentrations ◽  
Maternal Blood ◽  
Acth Secretion ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Acth Concentration ◽  
Negative Feedback Control

In sheep, parturition is initiated by an increase in fetal adrenal secretion of cortisol. In term fetuses, adrenocorticotropic hormone (ACTH) secretion is increased despite increasing plasma concentrations of cortisol. The present study was performed to investigate whether fetal ACTH secretion is under negative-feedback control by cortisol. Ten chronically catheterized fetal sheep (140 days gestation) were used in this study. Five were infused with hydrocortisone sodium succinate (10 micrograms/min) and five with 0.9% physiological saline for 5 h. Fetal and maternal blood samples were drawn at 1-h intervals. Infusion of hydrocortisone sodium succinate significantly increased fetal plasma cortisol concentration from 38.2 +/- 8.4 ng/ml to mean levels between 74.6 +/- 11.6 and 88.5 +/- 4.7 ng/ml. Fetal plasma ACTH concentration was significantly decreased from 129 +/- 36 to 31 +/- 5 pg/ml after 5 h of infusion. Infusion of saline did not alter fetal plasma cortisol or ACTH concentration. Neither of the infusions significantly altered maternal plasma concentrations of ACTH or cortisol, or fetal or maternal blood gases, or plasma concentrations of sodium or potassium. With one exception, all fetuses were born alive at 145 +/- 1 and 144 +/- 1 days gestation in the saline- and hydrocortisone sodium succinate-infused groups, respectively. The results of this study demonstrate that at 140 days gestation fetal ACTH secretion is under negative-feedback control by cortisol.

Does a decrease in cortisol negative feedback efficacy precede ovine parturition?

1987 ◽  
Vol 252 (3) ◽  
pp. R624-R627 ◽  
Author(s):  
C. E. Wood
Keyword(s):  
Sodium Nitroprusside ◽  
Negative Feedback ◽  
Plasma Cortisol ◽  
Feedback Inhibition ◽  
Cortisol Concentration ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Plasma Cortisol Concentration ◽  
Acth Concentration ◽  
Vascular Catheters

In sheep and other ruminants parturition is stimulated by increased secretion of fetal cortisol. The mechanism of this increased fetal adrenal activity is not known, but may be dependent on a decreased fetal hypothalamopituitary sensitivity to the negative feedback inhibition by cortisol. Seven fetal sheep (129-142 days gestation), chronically prepared with vascular catheters, were infused with cortisol (10 micrograms/min; n = 5) or vehicle (n = 4) for 5 h. Cortisol infusion increased fetal plasma cortisol to 50.8 +/- 4.3 ng/ml, approximately 33 ng/ml above the corresponding plasma cortisol concentration in the vehicle-infused fetuses. One hour after the end of the cortisol or vehicle infusion, infusion of sodium nitroprusside (50 micrograms/min, iv) increased fetal plasma adrenocorticotropin hormone (ACTH) concentration in both groups of fetuses. Results of another study (15) demonstrated that increases in fetal plasma cortisol of only 1.7 ng/ml for 5 h in younger (117-131 days gestation) fetuses completely blocked the fetal ACTH response to the same dose of nitroprusside. The results indicate that the preparturient rise in fetal ACTH is accompanied by a decrease in cortisol negative feedback.

Modulation of ovine fetal adrenocorticotropin secretion by androstenedione and 17beta-estradiol

1997 ◽  
Vol 272 (4) ◽  
pp. R1128-R1134 ◽  
Author(s):  
C. J. Saoud ◽  
C. E. Wood
Keyword(s):  
Negative Feedback ◽  
Sodium Succinate ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Estradiol Treatment ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Basal Plasma ◽  
Acth Concentration ◽  
Ovine Fetal

Parturition in sheep is initiated by increases in activity of the fetal hypothalamic-pituitary-adrenal axis. We have previously reported that cortisol negative feedback efficacy is decreased at the end of gestation. The present study was designed to test the hypothesis that increasing plasma estrogen and/or androgen concentrations in the fetus might increase plasma adrenocorticotropic hormone (ACTH) concentration, either by stimulating ACTH secretion or by altering the negative feedback effect of cortisol on ACTH. Fetal sheep were chronically catheterized and treated with no steroid (control), 17beta-estradiol, or androstenedione (each approximately 0.24 mg/day). After catheterization and implantation of steroid pellet, fetuses were subjected to two short (10 min) periods of sodium nitroprusside-induced hypotension with or without pretreatment with intravenous infusion of hydrocortisone sodium succinate (0.5 microg/min) to test fetal ACTH responsiveness to stress and cortisol negative feedback efficacy. Estradiol treatment significantly increased basal plasma ACTH and cortisol concentrations relative to control fetuses but did not interfere with the inhibition of ACTH secretion by cortisol. Fetal plasma ACTH responses to hypotension were significantly suppressed approximately 60% in both control and estradiol-treated groups. Androstenedione treatment significantly increased basal fetal plasma ACTH and decreased basal fetal plasma cortisol concentration. Androstenedione did not alter stimulated levels of fetal ACTH but did block the inhibition of stimulated ACTH by cortisol. We conclude that increased fetal cortisol and ACTH secretion at the end of gestation may be due to the combined effects of the gonadal steroids in that estradiol increases basal plasma ACTH secretion while androstenedione reduces cortisol negative feedback efficacy.

Effects of intravascular infusions of plasma on placental and systemic blood flow in fetal sheep

2006 ◽  
Vol 291 (6) ◽  
pp. H2884-H2888 ◽  
Author(s):  
George D. Giraud ◽  
J. Job Faber ◽  
Sonnet S. Jonker ◽  
Lowell Davis ◽  
Debra F. Anderson
Keyword(s):  
Umbilical Artery ◽  
Plasma Renin ◽  
Control Measures ◽  
Systemic Resistance ◽  
Flow Sensors ◽  
Systemic Blood Flow ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
The Common ◽  
Intravascular Catheters

Six singleton fetal sheep of 118–122 days gestational age were instrumented with flow sensors on the brachiocephalic artery, the postductal aorta, and the common umbilical artery and with arterial and venous intravascular catheters. At 125–131 days of gestation, we started week-long continuous recordings of flows and pressures. After control measures had been obtained, the fetuses were given continuous intravenous infusions of adult sheep plasma at an initial rate of 229 ml/day. After 1 wk of infusion, fetal plasma protein concentrations had increased from 34 to 78 g/l, arterial and venous pressures had increased from 42 to 64 and from 2.7 to 3.7 mmHg, and systemic resistance (exclusive of the coronary bed) had increased from 0.047 to 0.075 mmHg·min−1·ml−1, whereas placental resistance had increased from 0.065 to 0.111 mmHg·min−1·ml−1. Fetal plasma renin activities fell as early as 1 day after the start of infusion and remained below control (all changes P < 0.05). All flows decreased slightly although these decreases were not statistically significant. Thus the increase in arterial pressure was entirely due to an increase in systemic and placental resistances.

Fetal cardiovascular and endocrine responses to prolonged fetal hemorrhage

1986 ◽  
Vol 251 (2) ◽  
pp. R417-R424 ◽  
Author(s):  
R. A. Brace ◽  
C. Y. Cheung
Keyword(s):  
Blood Volume ◽  
Venous Pressure ◽  
Plasma Concentrations ◽  
Plasma Renin ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Moderate Volume ◽  
Circulating Levels ◽  
Initial Blood ◽  
Control Plasma

Twelve chronically catheterized fetal sheep averaging 131 +/- 1 (SE) days gestation (term = 145-150 days) were hemorrhaged an average of 30.8 +/- 1.8% of their initial blood volume over 2 h by removing blood at 10-min intervals. During the hemorrhage, fetal blood volume decreased by 14.3 +/- 1.4%, and arterial pressure (AP), venous pressure (VP), and heart rate (HR) did not change significantly, although fetal plasma renin activity (PRA), arginine vasopressin (AVP), and norepinephrine (NE) were elevated to 1.5-2.5 times their initial values (P less than 0.05). Circulating levels of PRA, AVP, and NE began to rise when 5-10, 10-15, and 20-30%, respectively, of the initial blood volume was removed. Three to five hours after the hemorrhage, blood volume had returned to normal, AP was reduced by an average of 6 mmHg, VP was unchanged, and HR was elevated by an average of 20 beat/min; PRA, AVP, and NE averaged two to three times control (P less than 0.05). Twenty-two hours after the hemorrhage, blood volume was 5.4 +/- 2.4% above control; AP and HR returned toward normal; VP was elevated by an average of 2 mmHg; PRA and NE levels remained elevated (P less than 0.05), but AVP was not different from control. Plasma concentrations of epinephrine, dopamine, and prolactin showed little change during or after the hemorrhage. Thus these studies indicate that the fetus rapidly returns its blood volume to normal after a substantial loss of blood. In addition, the fetal cardiovascular and endocrine responses to a prolonged fetal hemorrhage of moderate volume are substantially less than those that occur after rapid hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Corticosteroid-binding globulin (CBG) production by hepatic and extra-hepatic sites in the ovine fetus; effects of CBG on glucocorticoid negative feedback on pituitary cells in vitro

1995 ◽  
Vol 146 (1) ◽  
pp. 121-130 ◽  
Author(s):  
E T M Berdusco ◽  
K Yang ◽  
G L Hammond ◽  
J R G Challis
Keyword(s):  
Negative Feedback ◽  
Binding Capacity ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Free Cortisol ◽  
Corticosteroid Binding Globulin ◽  
Ovine Fetus ◽  
Acth Release

Abstract Plasma cortisol levels increase in fetal sheep during late gestation and this is associated with an increase in plasma corticosteroid-binding globulin (CBG) concentrations. However, the relative tissue sources of plasma CBG, the ontogeny of its biosynthesis and glycoform composition have not been established in the ovine fetus. Therefore we examined whether changes in plasma corticosteroid binding capacity (CBC) in fetal sheep during late gestation were associated with different patterns of glycosylation and reflected changes in tissue CBG expression. Since free cortisol is considered the bioactive fraction, we measured changes in the percent and absolute free cortisol in fetal plasma during late gestation. In order to examine whether CBG alters cortisol negative feedback at the level of the fetal pituitary, we also examined the effect of exogenous CBG in mediating the glucocorticoid-induced suppression of basal and corticotrophin-releasing hormone (CRH)-stimulated ACTH release from fetal pituitary cells in culture. The mean free cortisol concentration in plasma was not different between days 15 and 20 prior to parturition, and between 5 and 10 days prepartum, although it did rise between these times. Plasma CBC in chronically catheterized fetuses rose from 23·3 ± 4·6 ng/ml at day 115 to 86·5 ± 20·8 ng/ml at term and then decreased rapidly after birth. Between day 125 and day 140 of pregnancy approximately 10% of fetal plasma CBG was retarded by Concanavalin-A chromatography. This proportion increased at birth and attained adult values of >70% by one month of age. By Northern blotting the relative levels of CBG mRNA in the fetal liver did not change between days 100 and 125, then increased significantly at day 140, but declined at term and in newborn lambs. CBG mRNA was undetectable in total RNA from lung, kidney, hypothalamus and placentomes, but was present in the fetal pituitary at days 125 and 140. Reverse transcription-PCR was used to confirm the presence of CBG mRNA in pituitary tissue from term fetuses. In cultures of term fetal pituitary cells, added CBG attenuated the cortisol- but not the dexamethasone-mediated suppression of basal and CRH-stimulated ACTH release. We conclude that in fetal sheep there is an increase in the corticosteroid binding capacity of plasma during late pregnancy which regulates, in part, free cortisol levels in the circulation. The liver is the major site of CBG biosynthesis in the fetus and at least until day 140 of gestation the rise in plasma CBC is associated with an increase in hepatic CBG mRNA levels. The fetal pituitary was also established as a site of CBG production. Output of ACTH by cultured pituitary cells was inhibited by cortisol and this effect was diminished in the presence of added CBG. This study supports a role for systemic CBG in modulating the availability of cortisol to the fetal pituitary and suggests an additional way of modifying feedback effects of cortisol at the pituitary through its own production of CBG. Journal of Endocrinology (1995) 146, 121–130

Renin secretion in conscious Lyon hypertensive rats

1996 ◽  
Vol 271 (5) ◽  
pp. R1199-R1204 ◽  
Author(s):  
S. Bertolino ◽  
C. Julien ◽  
I. A. Medeiros ◽  
G. Cuisinaud ◽  
M. Vincent ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Feedback Inhibition ◽  
Plasma Renin ◽  
Renin Secretion ◽  
Infrarenal Aorta ◽  
Ang Ii ◽  
Salt Diet ◽  
Beta Adrenoceptor ◽  
Inflatable Cuff ◽  
Renin Content

To characterize the renin secretory profile in Lyon hypertensive (LH) rats, renin responses to reductions of arterial pressure and beta-adrenoceptor stimulation were assessed in conscious unrestrained LH (n = 13) and Lyon normotensive (LN, n = 14) rats under normal-salt diet. Mean arterial pressure (MAP) in the infrarenal aorta was recorded beat to beat for 3 h. Then, plasma renin concentration (PRC) was measured 1) in basal conditions, 2) during 10-mmHg stepwise reductions of MAP down to 60 mmHg using a chronically implanted aortic inflatable cuff, and 3) during isoprenaline infusion (62.5, 125, and 250 ng.kg-1.min-1 iv). Compared with LN, LH rats had an elevated MAP (146 +/- 3 vs. 111 +/- 1 mmHg, P < 0.001) and decreased PRC [4.2 +/- 0.6 vs. 8.2 +/- 0.8 ng angiotensin (ANG) I.ml-1.h-1, P < 0.001] and kidney renin content (216 +/- 14 vs. 1,149 +/- 103 micrograms ANG I.h-1.g-1, P < 0.001). Pressure-dependent renin release occurred below 90 mmHg in LN rats and below 80 mmHg in LH rats, and its sensitivity in the low-pressure range did not differ between strains. Isoprenaline-induced increases in PRC were weaker (P < 0.01) in LH than in LN rats. In additional LH and LN rats (n = 6-8), acute ANG II AT1-receptor blockade with losartan (20 mg/kg, followed by 10 mg.kg-1.h-1 iv for 2 h) induced lesser (P < 0.001) PRC increases in LH than in LN rats. Renin responses to isoprenaline remained blunted (P < 0.01) during losartan infusion in LH rats. We conclude that, in LH rats, renin secretion is independent of MAP in the range of its spontaneous variations and is poorly responsive to beta-adrenoceptor stimulation, the alteration of which cannot be explained by an enhanced feedback inhibition by ANG II.

Acidemia stimulates ACTH, vasopressin, and heart rate responses in fetal sheep

1989 ◽  
Vol 257 (2) ◽  
pp. R344-R349 ◽  
Author(s):  
C. E. Wood ◽  
H. G. Chen
Keyword(s):  
Heart Rate ◽  
Adrenocorticotropic Hormone ◽  
Plasma Concentrations ◽  
Plasma Renin ◽  
Fetal Sheep ◽  
Arterial Pco2 ◽  
Fetal Plasma ◽  
Arterial Blood ◽  
Arterial Ph ◽  
Highly Correlated

Adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP), and renin responses to hemorrhage are highly correlated to the hemorrhage-induced decreases in arterial pH. The present study was designed to test the responses of these three systems to acute fetal acidemia, produced by intravenous infusion of H+. HCl was infused into chronically catheterized fetal sheep at rates of 0.02 (n = 5), 0.10 (n = 6), and 0.50 (n = 5) meq/min. Infusions at rates of 0.10 and 0.50 meq/min significantly decreased fetal arterial pH and increased arterial PCO2. Fetal heart rate and plasma concentrations of ACTH, cortisol, and AVP were significantly increased during infusion of HCl at 0.5 meq/min. Neither fetal plasma renin activity nor fetal arterial blood pressure was significantly altered by any of the infusions. The results of these experiments suggest that fetal ACTH, AVP, and heart rate are stimulated by decreases in arterial pH and/or increases in arterial PCO2. We speculate that these responses are chemoreceptor mediated, although we cannot distinguish the apparent relative roles of peripheral and central chemoreceptors on the basis of the present study.

Sensitivity of cortisol-induced inhibition of ACTH and renin in fetal sheep

1986 ◽  
Vol 250 (5) ◽  
pp. R795-R802 ◽  
Author(s):  
C. E. Wood
Keyword(s):  
Plasma Renin Activity ◽  
Plasma Cortisol ◽  
Renin Angiotensin System ◽  
High Sensitivity ◽  
Plasma Renin ◽  
Cortisol Concentration ◽  
Renin Activity ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Plasma Cortisol Concentration

Previous experiments demonstrated that increases in ovine fetal plasma cortisol concentration to maximal stress levels suppressed fetal plasma renin activity and completely inhibited fetal adrenocorticotropin (ACTH) responses to subsequent stress. This study was designed to quantitate the suppressive action of cortisol on both ACTH and renin. Fetal sheep between 117 and 131 days gestation were surgically prepared with chronically implanted catheters. At least 4 days after surgery, vehicle or cortisol (0.25, 0.5, 1, 2, or 3 micrograms/min) were infused for 5 h. One hour after the end of the vehicle or cortisol infusion, fetal ACTH and renin secretion were stimulated by intravenous infusion of sodium nitroprusside. Cortisol infusions suppressed basal plasma renin activity (caused by suppression of plasma renin concentration) to degrees that were related to the increases in fetal plasma cortisol concentration. After cortisol infusions, renin responses to hypotension were apparently suppressed to degrees not obviously related to the rate of cortisol infusion. Fetal plasma ACTH responses to hypotension were completely suppressed by increases in total and unbound fetal plasma cortisol concentration 1.6 and 1.7 ng/ml, respectively. These results demonstrate a high sensitivity of the fetal hypothalamopituitary unit and renin-angiotensin system to cortisol.

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