Prenatal glucocorticoid exposure alters hypothalamic–pituitary–adrenal function and blood pressure in mature male guinea pigs

Banjanin, S.; Kapoor, Amita; Matthews, Stephen G.

doi:10.1113/jphysiol.2004.063669

Cited by 70 publications

(70 citation statements)

References 73 publications

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“…On PND28, adrenal:body weight ratio and adrenal weights were increased in LG-ACTH piglets. Similar results were found in guinea pigs after prenatal dexamethasone treatment (Liu et al 2001, Banjanin et al 2004). Our results also revealed an increased area of the adrenal cortex in these animals, indicating that internal morphological changes occurred, which increased the cortical mass.…”

Section: Discussionsupporting

confidence: 78%

Changes in endocrine and neurochemical profiles in neonatal pigs prenatally exposed to increased maternal cortisol

Kanitz¹,

Otten²,

Tuchscherer³

2006

Journal of Endocrinology

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Early life environmental factors are able to influence prenatal development and may cause structural and functional effects on hypothalamic-pituitary-adrenal (HPA) axis and neurotransmitter systems in the offspring. These effects seem to be species specific and may depend on the period of gestation when the factors are effective. Elevated maternal cortisol levels are assumed to play a crucial role as a programming factor during prenatal development. Thus, the present study was performed in order to examine the effects of increased maternal cortisol levels during mid-and late gestation on central and peripheral alterations of the HPA axis and brain neurotransmitter profiles in piglets. Endogenous cortisol release was induced by i.m. administration of ACTH to sows every second day either during mid-(day 49 until 75) or late gestation (day 85 until 107). Controls received injections of saline. ACTH treatment of sows during mid-and late gestation had no effects on the gestation length, the number of total born and the frequency of stillborn piglets. However, ACTH treatment during late gestation caused an increase of birth weight (P!0$04) and affected the organ:body weight ratios (brain and adrenal) in the offspring. There was an impact of increased maternal cortisol on the HPA axis and on central neurotransmitter systems in the offspring. ACTH treatment during mid gestation caused a significant decrease of plasma corticosteroid-binding globulin (CBG; P!0$03) and an increase of the noradrenergic activity in the locus coeruleus (LC) region (P!0$02). Elevated maternal cortisol during late gestation also produced a significant decrease of plasma CBG (P!0$05), but significantly increased the plasma noradrenaline (NA) concentration (P!0$02) and decreased the serotonergic activity in the LC at both postnatal day 1 (P!0$016) and day 28 (P!0$003). Furthermore, there were sex-specific effects of ACTH treatment on plasma CBG, NA and brain monoamine turnover, with more pronounced changes in male offspring. In conclusion, elevated maternal cortisol levels during mid-and late gestation in pigs affect growth, HPA axis and brain neurotransmitter systems in the offspring in a sex-specific manner. The observed alterations in endocrine and neurotransmitter systems are dependent on the gestational period. Late gestation appears to be a more sensitive phase for cortisol-induced programming in pigs. Moreover, the present data show that there are marked developmental differences between laboratory animals and domestic pigs, and highlight the importance of speciesspecific studies on prenatal influences.

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Section: Discussionsupporting

confidence: 78%

Changes in endocrine and neurochemical profiles in neonatal pigs prenatally exposed to increased maternal cortisol

Kanitz¹,

Otten²,

Tuchscherer³

2006

Journal of Endocrinology

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“…These receptors mediate the effects of cortisol both centrally and peripherally. Sexually dimorphic changes in GR and MR expression in the brain and central nervous system in the presence of increased pre-natal glucocorticoid have previously been reported in a number of animal models (Banjanin et al 2004;Lingas et al 1999;Halasz et al 1997). Maternal administration of glucocorticoid during late gestation in the guinea-pig results in an increase in GR and MR mRNA of the central nervous system in only male offspring, as shown by Banjanin et al (2004).…”

Section: Fetal Grs and Mrsmentioning

confidence: 78%

Sexually dimorphic effects of maternal asthma during pregnancy on placental glucocorticoid metabolism and fetal growth

Clifton

2005

Cell Tissue Res

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Human pregnancy is associated with sexually dimorphic differences in mortality and morbidity of the fetus with the male fetus experiencing the poorest outcome following complications such as pre-eclampsia, pre-term delivery and infection. The physiological mechanisms that confer these differences have not been well characterised in the human. Work conducted on the effect of maternal asthma during pregnancy, combining data collected from the mother, placenta and fetus has found some significant sex-related mechanistic differences associated with fetal growth in both normal pregnancies and pregnancies complicated by asthma. Specifically, sexually dimorphic differences have been found in placental glucocorticoid metabolism in male and female fetuses of normal pregnancies. In response to the presence of maternal asthma, only the female fetus alters placental glucocorticoid metabolism resulting in decreased growth. The male fetus does not alter placental function or growth in response to maternal asthma. As a result of the alterations in glucocorticoid metabolism in the female, downstream changes occur in pathways regulated by glucocorticoids. These data suggest that the female fetus adjusts placental function and reduces growth to compensate for maternal disease. However, the male fetus continues to grow in response to maternal asthma with no changes in placental function. This response by the male fetus may partially contribute to the increased risk of morbidity and mortality in this sex.

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“…Evidence from animal studies, however, seems to dispute this. Programming of the HPA axis by prenatal exposure to glucocorticoids was shown to be dependent on increasing age in studies of male guinea pigs (30,31). Glucocorticoids-exposed 80-day-old guinea pigs showed a reduction in basal and activated pituitary-adrenal function compared with unexposed animals, while this effect was no longer observed at the age of 150 days.…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic–pituitary–adrenal axis activity in adults who were prenatally exposed to the Dutch famine

Rooij¹,

Painter²,

Phillips³

et al. 2006

eur j endocrinol

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Objective: The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be susceptible to fetal programming, the process by which an adverse fetal environment elicits permanent physiological and metabolic alterations predisposing to disease in later life. It is hypothesized that fetal exposure to poor circumstances alters the set point of the HPA axis, leading to increased HPA axis activity and subsequent increased cortisol concentrations. In this study, we tested the hypothesis that prenatal exposure to famine during different periods of gestation is associated with increased activity of the HPA axis. Design and methods: We assessed plasma cortisol concentrations after a dexamethasone suppression and an ACTH 1-24 -stimulation test in a group of 98 men and women randomly sampled from the Dutch famine birth cohort. Cohort members were born as term singletons around the 1944-1945 Dutch famine. Results: Cortisol profiles after dexamethasone suppression and ACTH 1-24 stimulation were similar for participants exposed to famine during late, mid-or early gestation (PZ0.78). Cortisol concentrations after dexamethasone suppression test did not differ between those exposed and those unexposed to famine in utero (mean difference K2% (95% confidence interval (CI) K27 to 23)). Neither peak cortisol concentration (20 nmol/l (95% CI K27 to 66)), cortisol increment (K5 nmol/l (95% CI K56 to 47)) or cortisol area under the curve post-ACTH 1-24 injection (4% (95% CI K4 to 12)) differed between exposed and unexposed participants. Conclusions: Prenatal famine exposure does not seem to affect HPA axis activity at adult age, at least not at the adrenal level. This does not exclude altered HPA axis activity at the levels of the hippocampus and hypothalamus.European Journal of Endocrinology 155 153-160

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Prenatal glucocorticoid exposure alters hypothalamic–pituitary–adrenal function and blood pressure in mature male guinea pigs

Cited by 70 publications

References 73 publications

Changes in endocrine and neurochemical profiles in neonatal pigs prenatally exposed to increased maternal cortisol

Changes in endocrine and neurochemical profiles in neonatal pigs prenatally exposed to increased maternal cortisol

Sexually dimorphic effects of maternal asthma during pregnancy on placental glucocorticoid metabolism and fetal growth

Hypothalamic–pituitary–adrenal axis activity in adults who were prenatally exposed to the Dutch famine

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