Foetal Plasma Corticosteroids and the Initiation of Parturition in Sheep

Bassett, J. M.; Thorburn, G. D.

doi:10.1677/joe.0.0440285

Cited by 282 publications

(104 citation statements)

References 3 publications

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“…In addition, we have demonstrated that the same ACTH infusion regimen in intact fetuses is not sufficient to significantly advance parturition or adrenal maturation. Labour in all groups of fetuses in this study was characterised by an increase in plasma cortisol concentrations beginning around 14 days before term, as shown previously (Bassett & Thorburn 1969, Jacobs et al 1994, but this was not associated with an increase in plasma ir-ACTH concentrations in ACTH (1-24) -infused HX fetuses. This observation was confirmed by assaying ir-ACTH concentrations in two distinct RIAs, thus reinforcing the biological conclusions which may be drawn from the data.…”

Section: Discussionsupporting

confidence: 79%

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

Poore¹,

Young²,

Canny³

et al. 1998

Journal of Endocrinology

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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 from the time of surgery (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 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 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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Section: Discussionsupporting

confidence: 79%

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

Poore¹,

Young²,

Canny³

et al. 1998

Journal of Endocrinology

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“…It is well established that parturition in the sheep is dependent on activation of the fetal hypothalamicpituitary-adrenal axis during late gestation and a concurrent increase in fetal plasma cortisol concentrations (Bassett & Thorburn 1969, Liggins 1976, Thorburn & Challis 1979. There is also an increase in production of oestradiol (E 2 ) from the placenta that follows the increase in circulating glucocorticoid concentrations (Challis & Brooks 1989).…”

Section: Introductionmentioning

confidence: 99%

Effects of cortisol and oestradiol on hepatic 11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor proteins in late-gestation sheep fetus

Gupta¹,

Alfaidy²,

Holloway³

et al. 2003

Journal of Endocrinology

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In the late-gestation sheep, increased fetal plasma cortisol concentration and placental oestradiol (E 2 ) output contribute to fetal organ maturation, in addition to the onset of parturition. Both cortisol and E 2 are believed to regulate the enzyme 11 -hydroxysteroid dehydrogenase type 1 (11 -HSD1), which interconverts bioactive 11-hydroxy glucocorticoids and their inactive 11-keto metabolites. 11 -HSD1, abundantly expressed in fetal liver, operates primarily as a reductase enzyme to produce bioactive cortisol and thus regulates local hepatic glucocorticoid concentrations. Cortisol acts through the glucocorticoid receptor (GR) present in the liver. In this study, we examined the effects of cortisol and E 2 on hepatic 11 -HSD1 and GR in the liver of chronically catheterized sheep fetuses treated with saline (n=5), cortisol (1·35 mg/ h; n=5), saline+4-hydroxyandrostendione, a P450 aromatase inhibitor (4-OHA; 1·44 mg/h; n=5), or cortisol+4-OHA (n=5). Cortisol infusion resulted in increased plasma concentrations of fetal cortisol and E 2 ; concurrent administration of 4-OHA attenuated the increase in plasma E 2 concentrations. Using immunohistochemistry, we showed that fetal hepatocytes expressed both 11 -HSD1 and GR proteins. Cortisol treatment increased GR in both cytosol and nuclei of hepatocytes; concurrent administration of 4-OHA was associated with distinct nuclear GR staining. Western blot revealed that cortisol, in the absence of increased E 2 concentrations, significantly increased concentrations of 11 -HSD1 (34 kDa) and GR (95 kDa) proteins. 11 -HSD1 enzyme activity was measured in the liver microsomal fraction in the presence of [ + (dehydrogenase activity) respectively. 11 -HSD1 reductase activity was significantly greater in the presence of cortisol. In summary, we found that, in sheep during late gestation, cortisol increased both 11 -HSD1 and GR in the fetal liver, and these effects were accentuated in the absence of increased E 2 .

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“…Other methods. -DNA, proteins, ACTH receptors and plasma corticosteroids were assayed as described elsewhere (Durand et al, 1978 ;Durand, 1979 (Rees et al, 1975 ;Challis et al,1977a ;Jones et al,1977a) and confirm that ACTH levels rise only in the very last days of gestation, when cortisol levels are already elevated (Bassett and Thorburn, 1969 ;Liggins et al, 1973 Liggins (19b9), whereas large doses of ACTH anticipated the increase in adrenal weight (Liggins,1968). Figure 2 shows that the infusion of 0.1 mg/24 h of ACTH into the sheep fetus between days 115 and 120 resulted in a 4-fold d increment in adrenal membrane protein content and a 2-fold increase in DNA concentrations.…”

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confidence: 99%