Activation of pituitary-adrenal function in fetal sheep by corticotrophin-releasing factor and arginine vasopressin

1990 ◽  
Vol 124 (1) ◽  
pp. 27-35 ◽  
Author(s):  
A. N. Brooks ◽  
A. White
Keyword(s):  
Negative Feedback ◽  
Arginine Vasopressin ◽  
Plasma Concentrations ◽  
Premature Delivery ◽  
Fetal Sheep ◽  
Feedback Effects ◽  
Adrenal Axis ◽  
Corticotrophin Releasing Factor ◽  
Endogenous Cortisol ◽  
Pituitary Adrenal Axis

ABSTRACT In sheep, birth is preceded by an increase in fetal plasma concentrations of ACTH and cortisol. Activation of the fetal pituitary-adrenal axis is pivotal to the onset of parturition in this species and may be regulated, at least in part, by corticotrophin-releasing factor (CRF). Pulsed administration of CRF has been shown to activate the fetal pituitary-adrenal axis in immature fetal sheep. However, pituitary ACTH responsiveness declined after continued administration of CRF, as a result of increasing negative feedback effects of increased concentrations of endogenous cortisol. To test the hypothesis that arginine vasopressin (AVP) is required, in addition to CRF, to produce the necessary trophic stimulus to the pituitary-adrenal axis, we administered saline, CRF (1 μg), AVP (200 ng) or CRF plus AVP as pulses every 4 h for 7 days to fetal sheep beginning at days 117–120 of pregnancy (term =145 days). Pituitary-adrenal responses were assessed by measuring plasma concentrations of immunoreactive (ir) ACTH and cortisol in response to one of the pulses on each of the 7 days of treatment. On day 1, CRF and AVP significantly increased plasma concentrations of ir-ACTH and there was a synergistic interaction when the two peptides were given together (P<0·05). However, as pulsed treatment continued there was a decline in the pituitary ir-ACTH response to all treatments (P<0·05). This decline in pituitary response occurred over a much longer period of time when CRF and AVP were given together when compared with the two peptides given separately. In contrast, the cortisol response to endogenously released ir-ACTH after administration of CRF, AVP or CRF plus AVP was small on day 1 but gradually increased as treatment progressed. This was particularly apparent when the two peptides were given together. A significant inverse correlation (r = 0·781, P<0·01) between basal cortisol concentrations and the ir-ACTH response to CRF plus AVP was observed over the 7 days of treatment. Premature delivery was not induced by any of the treatments despite significant increases in fetal adrenal weight. Furthermore, there were no changes in the circulating maternal plasma concentrations of progesterone or oestrone during the 7 days of the experiment. We conclude that combination of CRF and AVP administered as pulses to immature fetal sheep results in a greater degree of pituitary-adrenal activation when compared with the two peptides given independently. However, even after this combined treatment regimen pituitary responsiveness eventually declines, an effect which may be due to increased negative feedback effects of increased endogenous cortisol. Journal of Endocrinology (1990) 124, 27–35

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

1987 ◽  
Vol 65 (6) ◽  
pp. 1186-1192 ◽  
Author(s):  
Laurie J. Norman ◽  
John R. G. Challis
Keyword(s):  
Negative Feedback ◽  
Arginine Vasopressin ◽  
Late Pregnancy ◽  
Feedback Effect ◽  
Plasma Acth ◽  
Fetal Sheep ◽  
Corticotrophin Releasing Factor ◽  
Basal Release ◽  
Sheep Fetus ◽  
Acth Release

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. Our results suggest different controls of basal and stimulated ACTH release from the pituitary at d 113–116 of gestation. Our findings would be consistent with the pituitary as a level of action for the negative feedback effect of corticosteroids on stimulated ACTH release throughout the last third of pregnancy in fetal sheep.

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

1988 ◽  
Vol 119 (3) ◽  
pp. 389-395 ◽  
Author(s):  
A. N. Brooks ◽  
J. R. G. Challis
Keyword(s):  
Opioid Receptors ◽  
Statistical Significance ◽  
Plasma Concentrations ◽  
Specific Effect ◽  
Hypothalamic Pituitary Adrenal Axis ◽  
Endogenous Opioids ◽  
Fetal Sheep ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Pituitary Adrenal Axis

ABSTRACT 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 μg), 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 <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. We conclude that opioid receptors capable of mediating the effects of exogenously administered opioid peptides on the pituitary-adrenal axis are present in fetal sheep by days 123–130. However, we have been unable to demonstrate tonic control of this axis by endogenous opioids, since naloxone is ineffective when given alone. J. Endocr. (1988) 119, 389–395

ACTH and cortisol responses to hypotension in fetal sheep after a prior CRF injection

1992 ◽  
Vol 262 (3) ◽  
pp. E325-E329
Author(s):  
D. R. Kerr ◽  
M. I. Castro ◽  
N. K. Valego ◽  
N. M. Rawashdeh ◽  
J. C. Rose
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Plasma Acth ◽  
Fetal Sheep ◽  
Feedback Effects ◽  
Maximal Stimulation ◽  
Endogenous Cortisol ◽  
Before And After ◽  
Cortisol Responses ◽  
Releasing Factors ◽  
Stimulation Of

To determine whether an ovine corticotropin-releasing factor (oCRF) injection modifies adrenocorticotropic hormone (ACTH) and cortisol responses to hypotension and whether the effect of any interactions between these stimuli changes across gestation, we studied chronically cannulated fetal lambs of 103-113 ("immature") and 133-139 days gestation ("mature"). Experimental groups received 500 ng/kg oCRF injections and 6 h later had arterial pressure reduced 20% for 10 min with nitroprusside. Blood samples were obtained before and after each manipulation. Controls received vehicle instead of oCRF. The oCRF increased plasma cortisol levels from 2.1 +/- 0.4 to 14.2 +/- 4.7 (SE) ng/ml in immature and 44.9 +/- 2.2 to 102.8 +/- 15 ng/ml in mature animals. In mature fetuses the oCRF did not alter plasma ACTH and cortisol increases due to hypotension. In immature animals ACTH increases were normal but cortisol increases were eliminated. This suggests that the CRF caused maximal stimulation of the adrenal gland. In older fetuses, it appears that the action of ACTH-releasing factors, secreted in response to arterial hypotension, can overcome the negative feedback effects of elevations in endogenous cortisol.

Centrally Administered Murine-Leptin Stimulates the Hypothalamus-Pituitary- Adrenal Axis through Arginine-Vasopressin

2000 ◽  
Vol 71 (6) ◽  
pp. 366-374 ◽  
Author(s):  
Isao Morimoto ◽  
Shigeki Yamamoto ◽  
Keiko Kai ◽  
Takashi Fujihira ◽  
Emiko Morita ◽  
...  
Keyword(s):  
Arginine Vasopressin ◽  
Adrenal Axis ◽  
Hypothalamus Pituitary Adrenal Axis ◽  
Pituitary Adrenal Axis
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