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Studies on the role of ACTH in the regulation of adrenal responsiveness and the timing of parturition in the ovine fetus

Studies on the role of ACTH in the regulation of adrenal responsiveness and the timing of parturition in the ovine fetus
Studies on the role of ACTH in the regulation of adrenal responsiveness and the timing of parturition in the ovine fetus

A dramatic late-gestation increase in fetal plasma cortisol concentrations is critical for the timing of parturition in the sheep. This increase appears to depend upon an intact hypothalamo-pituitary unit and is characterised by increasing responsiveness of the fetal adrenal gland to ACTH. ACTH has been postulated as the critical determinant of the late-gestation cortisol increase; however, recent evidence has suggested that other factors, including the ACTH precursor, pro-opiomelanocortin, may also be involved. To further define the role of ACTH in determining the timing of parturition and the responsiveness of the fetal adrenal gland, intact (INT/ACTH) and hypophysectomised (HX/ACTH) fetuses received a continuous infusion of ACTH(1-24) from the time of surgery (approximately 115 days gestational age (GA)) at a rate we have previously shown to generate normal fetal cortisol concentrations and term parturition in HX fetuses. A third group of saline-infused intact fetuses (INT/SAL) served as the control group. Adrenal responsiveness was assessed by cortisol responses to ACTH(1-24) challenges at 120, 130 and 140 days GA. There were no differences between the three groups of fetuses in the timing of parturition, the late-gestation increase in cortisol concentrations or the size of the adrenal cortex. In both INT/SAL and INT/ACTH fetuses, there were significant increases in basal immunoreactive-ACTH concentrations with advancing GA, although no such increase was observed in HX/ACTH fetuses. The proportion of total ACTH immunoreactivity present in low molecular weight (LMW) forms in INT/ACTH fetuses was greater than that in INT/SAL fetuses, while the level of LMW ACTH in HX/ACTH fetuses was intermediate. Both ACTH(1-24)-infused groups of fetuses had dramatically enhanced adrenal responsiveness to ACTH(1-24) at all GAs tested when compared with INT/SAL fetuses and there was a correlation (in rank order) between the proportion of LMW ACTH immunoreactivity and adrenal responsiveness. From these observations it appears that there is a separate regulation of adrenal responsiveness from basal cortisol concentrations and that an increase in basal cortisol concentrations can occur in the absence of an increase in basal ACTH concentrations. Furthermore, an increase in adrenal responsiveness does not appear to predict the timing of parturition nor basal cortisol concentrations. Taken together with previous studies it appears that ACTH plays an essential role in maintaining the growth of the fetal adrenal and enhancing its responsiveness, but a late-gestation increase in ACTH concentrations is not required to regulate basal cortisol concentrations or the timing of parturition.

Adrenal Glands, Adrenocorticotropic Hormone, Animals, Fetal Blood, Gestational Age, Hypophysectomy, Labor, Obstetric, Pregnancy, Sheep
0022-0795
161-71
Poore, K.R.
b9529ba3-6432-4935-b8fd-6e382f11f0ad
Young, I R
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Canny, B J
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Thorburn, G D
874a9161-416c-4344-b295-30239242f532
Poore, K.R.
b9529ba3-6432-4935-b8fd-6e382f11f0ad
Young, I R
52173df6-255b-4cd7-917a-69d52f3623e7
Canny, B J
28dd8cd7-98e8-4c48-8658-b856d2aed6dd
Thorburn, G D
874a9161-416c-4344-b295-30239242f532

Poore, K.R., Young, I R, Canny, B J and Thorburn, G D (1998) Studies on the role of ACTH in the regulation of adrenal responsiveness and the timing of parturition in the ovine fetus. Journal of Endocrinology, 158 (2), 161-71.

Record type: Article

Abstract

A dramatic late-gestation increase in fetal plasma cortisol concentrations is critical for the timing of parturition in the sheep. This increase appears to depend upon an intact hypothalamo-pituitary unit and is characterised by increasing responsiveness of the fetal adrenal gland to ACTH. ACTH has been postulated as the critical determinant of the late-gestation cortisol increase; however, recent evidence has suggested that other factors, including the ACTH precursor, pro-opiomelanocortin, may also be involved. To further define the role of ACTH in determining the timing of parturition and the responsiveness of the fetal adrenal gland, intact (INT/ACTH) and hypophysectomised (HX/ACTH) fetuses received a continuous infusion of ACTH(1-24) from the time of surgery (approximately 115 days gestational age (GA)) at a rate we have previously shown to generate normal fetal cortisol concentrations and term parturition in HX fetuses. A third group of saline-infused intact fetuses (INT/SAL) served as the control group. Adrenal responsiveness was assessed by cortisol responses to ACTH(1-24) challenges at 120, 130 and 140 days GA. There were no differences between the three groups of fetuses in the timing of parturition, the late-gestation increase in cortisol concentrations or the size of the adrenal cortex. In both INT/SAL and INT/ACTH fetuses, there were significant increases in basal immunoreactive-ACTH concentrations with advancing GA, although no such increase was observed in HX/ACTH fetuses. The proportion of total ACTH immunoreactivity present in low molecular weight (LMW) forms in INT/ACTH fetuses was greater than that in INT/SAL fetuses, while the level of LMW ACTH in HX/ACTH fetuses was intermediate. Both ACTH(1-24)-infused groups of fetuses had dramatically enhanced adrenal responsiveness to ACTH(1-24) at all GAs tested when compared with INT/SAL fetuses and there was a correlation (in rank order) between the proportion of LMW ACTH immunoreactivity and adrenal responsiveness. From these observations it appears that there is a separate regulation of adrenal responsiveness from basal cortisol concentrations and that an increase in basal cortisol concentrations can occur in the absence of an increase in basal ACTH concentrations. Furthermore, an increase in adrenal responsiveness does not appear to predict the timing of parturition nor basal cortisol concentrations. Taken together with previous studies it appears that ACTH plays an essential role in maintaining the growth of the fetal adrenal and enhancing its responsiveness, but a late-gestation increase in ACTH concentrations is not required to regulate basal cortisol concentrations or the timing of parturition.

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Poore et al 1998 J Endo 158 pp161-171
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Published date: August 1998
Keywords: Adrenal Glands, Adrenocorticotropic Hormone, Animals, Fetal Blood, Gestational Age, Hypophysectomy, Labor, Obstetric, Pregnancy, Sheep

Identifiers

Local EPrints ID: 414069
URI: http://eprints.soton.ac.uk/id/eprint/414069
ISSN: 0022-0795
PURE UUID: 59374c30-9d8d-495e-97d9-94d13f202e6b
ORCID for K.R. Poore: ORCID iD orcid.org/0000-0002-1455-0615

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Date deposited: 13 Sep 2017 16:31
Last modified: 16 Mar 2024 03:29

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Contributors

Author: K.R. Poore ORCID iD
Author: I R Young
Author: B J Canny
Author: G D Thorburn

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