- Email: [email protected]
P1-72 Adrenal gene expression in sheep is altered by maternal dexamethasone treatment in early gestation
S102
Posters
P1-70 Pain responses and fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis of infants born to opioid dependent mothers; a pilot study E.M. Hurrion *. Mater Mothers Hospital, Brisbane, Qld., Australia E-mail: [email protected]
3.5
170
2.5 2 1.5 1
Cases
0.5
Heart Rate
Cortisol (ug/dL)
3
Cases
150
Controls
Post
160 150
Cases Controls
140 130 120
0
40
20
C-M (n=12) C-F (n=14) dex-M (n=15) dex-F (n=10)
10
0
15
60
0
15
60
Minutes
Conclusions: Exposure of fetal sheep at 40 days gestation to maternal dexamethasone treatment results in a decreased hypothalamic-pituitary-adrenal response after birth in females but not males. P1-72 Adrenal gene expression in sheep is altered by maternal dexamethasone treatment in early gestation
170 Heart Rate
Cortisol (ug/dL)
1
C-M (n=12) C-F (n=14) dex-M (n=15) dex-F (n=10)
Minutes
Pre
Cases
0.5
150
0
3.5
1.5
50
200
0
120
Time Relative to Injection
Controls
60
50
130
40 min
2
Cortisol
70
250
100
Cortisol and heart rate readings at 48 h.
2.5
ACTH
300
140
Time Relative to Injection
3
Objective: To evaluate the effects of prenatal dexamethasone exposure on responses to two procedures that are conducted routinely as standard agricultural procedures in young Australian sheep. These procedures are placement of a tight rubber ligature around the base of the tail and, in males, a similar procedure to cause castration. Method: Pregnant ewes carrying singleton fetuses were randomized to control (2ml saline/ewe) or dexamethasone (dex) treatment (0.14mg/kg ewe weight) consisting of four intramuscular injections at 12-hourly intervals over 48 hours on days 40 41 (term 150 days). At 31 days of postnatal age, a rubber ring was placed around the base of the tail of each lamb, and in males, a ring was also placed around the scrotum to cause castration. Blood samples were taken from the jugular vein before commencement of the first procedure (0 minute) and 15 and 60 minutes after completion of the ring placements. ACTH and cortisol were measured by 125 I radioimmunoassay. Results: ACTH levels at 60 minutes in treatment females (dexF) were significantly lower than in treatment males (dex-M) (P = 0.006). Cortisol levels at 15 minutes in dex-F were significantly lower than in control females (C-F) (P = 0.005). At 60 minutes, cortisol levels in dex-F were lower than in control males (C-M) (P = 0.01) and treated males (dex-M) (P = 0.002). Cortisol levels in C-F were lower than in C-M (P = 0.029).
30
160
100
0
20 min
S. Li1,2 *, T.J.M. Moss1,2,4 , I. Nitsos1 , G. Polglase1,2 , T. Braun3 , J.R.G. Challis3 , J.P. Newnham1,2 . 1 School of Women’s and Infants’ Health, the University of Western Australia, WA, Australia, 2 Women and Infants Research Foundation, WA, Australia, 3 Depts of Physiology and Obstetrics and Gynecology, the University of Toronto, Canada, 4 Combined Universities Centre for Rural Health, WA, Australia E-mail: [email protected]
110
Controls Baseline
P1-71 Prenatal dexamethasone exposure results in gender-specific responses of the hypothalamic-pituitary-adrenal axis in lambs
pg/ml
Aims: To establish whether well full-term infants born to methadone (MD)/buprenorphine (bup) maintained mothers show evidence of fetal programming of HPA axis through altered baseline cortisol levels/cortisol responses to pain in the first year of life. Study design: Prospective cohort study of infants antenatally exposed to MD/bup versus comparison group of controls. Responses to routine immunisations up to 1 year were examined using heart rate and salivary cortisol levels. Subjects: Pilot study of 5 opioid-exposed infants and 4 controls. Outcome measures: Salivary cortisol levels at baseline and 20/40 minutes after painful stimulus. Heart rate at baseline and after painful stimulus. Results: After birth exposed infants have a high baseline cortisol and “downer” response to pain, with a lower baseline heart rate but also a “downer” response to pain (Fig. 1). In infancy baseline cortisol levels decline and cross over those of controls (as reported in animal model) whilst baseline heart rate is persistently lower than controls (Fig. 2). Complete 1-year data available October 2007.
controls (sample size based on this pilot data). Confirmation of pilot study findings could partly explain the recognised susceptibility of exposed individuals to ADHD, anxiety, depression and drug abuse.
ng/ml
their first prenatal visit (on average 12th week of pregnancy). As the diurnal variation in cortisol is high, only those women who gave blood before 10 a.m. were selected. This resulted in a total of 288 women for the analysis. Outcome measures: Linear regression coefficients and standard errors [SE] for continuous birth weight (grams) at term. Results: Maternal cortisol, standardized for the time of day and the pregnancy duration at blood collection, ranged from 53.77 to 291.25 mg/L and was dichotomized into low and high (>50th percentile) cortisol level. High maternal cortisol was inversely related to birth weight at term (regression coefficient [SE]: 176.89 [53.86]; P = 0.001). After adjustment for covariates (maternal age, pre-pregnancy height and BMI, education, smoking, parity, gestational age at birth, and fetal gender) high maternal cortisol was still significantly inversely related to birth weight (regression coefficient [SE]: 139.70 [47.35]; P = 0.003). Conclusions: High maternal cortisol during early pregnancy is related to lower birth weight at term.
48 hours 5-7 days 2 months 4 months 6 months 1 year
48 hours 5-7 days 2 months 4 months 6 months
Collection
Collection
Cortisol level and heart rate at baseline. CONCLUSIONS: This pilot study provides important “proof of concept” data (and first human data) to support author’s hypothesis that antenatal opioid exposure results in fetal programming of the HPA axis. A larger study is planned of 80 exposed infants & 80
S. Li1,2 *, I. Nitsos1 , G. Polglase1,2 , T. Braun3 , T.J.M. Moss1,2,4 , J.R.G. Challis3 , J.P. Newnham1,2 . 1 School of Women’s and Infants’ Health, the University of Western Australia, WA, Australia, 2 Women and Infants Research Foundation, WA, Australia, 3 Depts of Physiology and Obstetrics and Gynecology, the University of Toronto, Canada, 4 Combined Universities Centre for Rural Health, WA, Australia E-mail: [email protected] Objective: To determine if alterations in postnatal adrenal gene expression contribute to hypothalamic-pituitary-adrenal (HPA) programming resulting from maternal dexamethasone (dex) administration in early pregnancy.
Posters Method: Pregnant ewes carrying singleton fetuses were randomized to control (2 ml saline/ewe) or dexamethasone (dex) treatment (0.14 mg/kg ewe weight) consisting of four intramuscular injections at 12-hourly intervals over 48 hours on days 40 41 (term 150 days). Adrenal tissue was collected from the offspring at seven months postnatal age. Levels of mRNA of steroidogenic enzymes P450c17 and 3b hydroxysteroid dehydrogenase (3b HSD), ACTH receptor (ACTHr), glucocorticoid receptor (GR), steroidogenic acute regulatory protein (StAR), and 11b hydroxysteroid dehydrogenase 2 (11b HSD2) were determined using quantitative RT-PCR. Results: Dex-females (n = 5) had lower levels of 11b HSD2 than control females (n = 6) (P = 0.039) and dex-males (n = 7) (P = 0.042). In males, dex-treated animals had significant increases in levels of StAR (P < 0.001) and 3b HSD (P = 0.034) when compared with gendermatched controls (n = 5). ACTHr levels were similar in treated and control males and females. GR and P450c17 mRNA levels were similar across all groups. Conclusions: Maternal dexamethasone administration in early pregnancy resulted in changes in adrenal gene expression levels when measured in the offspring seven months after birth. These effects on adrenal gene expression may contribute to altered HPA responsiveness following prenatal corticosteroid exposure. P1-73 Aldosterone does not increase cell cycle activity in near-term fetal sheep cardiomyocytes S. Louey1 *, P.F. O’Tierney1 , N.N. Chattergoon1 , G.D. Giraud1,2,3,4 , K.L. Thornburg1,2,3 . 1 Heart Research Center; Departments of 2 Medicine (Cardiovascular Medicine) and 3 Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239 3098, USA, 4 Portland VA Medical Center, Portland, OR 97207 1034, USA E-mail: Email: [email protected] We have recently shown that sub-pressor doses of cortisol increase cell cycle activity in near-term fetal sheep cardiomyocytes. Cortisol acts with similar affinity via the glucocorticoid and mineralocorticoid receptors, whereas aldosterone acts exclusively via the mineralocorticoid receptor. Aims: The aim of this study was to determine the effect of aldosterone infusion on cell cycle activity in near-term fetal sheep cardiomyocytes. Study design and Subjects: Chronically instrumented fetal sheep (132d gestational age, GA; term ~145d GA) were infused with subpressor doses of aldosterone (5 mg/hr, n = 5) or vehicle (n = 5) for 48 hours. At 134d GA, fetal hearts were enzymically dissociated. Outcome measures: Isolated cardiomyocytes were analysed for size, maturational state and cell cycle activity. Data are expressed as mean±SD. Results: Aldosterone infusion increased circulating levels from 235±100 pg/ml to 1356±561 pg/ml (P < 0.05). Fetal body and heart weights were not different between the vehicle and aldosteroneinfused fetuses. Isolated cardiomyocyte size and maturational state were not different between groups. Cell cycle activity, assessed by staining for Ki-67, was not different between study groups (left ventricle: vehicle 5.6±1.4%, aldosterone 8.8±4.8%; right ventricle: vehicle 7.6±3.6%, aldosterone 6.6±3.2%). Conclusions: Forty-eight hours of aldosterone infusion did not significantly increase cell cycle activity in near-term fetal sheep cardiomyocytes, although there was a trend for increased staining for Ki-67 in the left ventricle. It is likely that increased cell cycle activity in response to cortisol infusion is mediated via the glucocorticoid receptor alone.
S103 P1-74 Placental multidrug resistance phosphoglycoprotein (ABCB1) expression is reduced by glucocorticoids during late gestation in the rat P.J. Mark *, S. Augustus, D.P. Hewitt, B.J. Waddell. School of Anatomy and Human Biology, The University of Western Australia, Perth, Western Australia 6009, Australia E-mail: [email protected] Aims: Fetal glucocorticoid excess programs adverse outcomes in adult offspring, including hypertension and insulin resistance. Access of maternal glucocorticoids to the placenta/fetus is regulated by the placental 11b-HSD enzymes, but recent studies show that glucocorticoid access to placental GR is also restricted by the multidrug resistance phosphoglycoprotein (ABCB1) [1]. However, the expression and regulation of placental ABCB1 in vivo remain poorly understood. Here we measured rat placental expression of the two ABCB1 genes (Abcb1a and Abcb1b) in normal pregnancy and following altered exposure to progesterone or glucocorticoid. Study design: Placentas were collected on days 16 and 22 of normal pregnancy and after either dexamethasone treatment (0.75 mg/ml drinking water from day 13) or ovariectomy (day 16) plus full estrogen and partial (one third) progesterone replacement. Outcome measures: Basal and labyrinth zone expression of Abcb1a and Abcb1b mRNA were determined by qRT-PCR. Results: Labyrinthine expression of both Abcb1a and Abcb1b greatly exceeded that in basal zone, and did not change significantly between days 16 and 22. Dexamethasone reduced Abcb1a only in the labyrinth zone at day 22, but had no effect on Abcb1b. Partial progesterone withdrawal had no effect on expression of Abcb1a or Abcb1b in either placental zone on day 22. Conclusions: Placental expression of Abcb1a and Abcb1b was relatively constant over the final third of rat pregnancy and was unaffected a premature reduction in progesterone. Increased glucocorticoid exposure, however, decreased labyrinthine Abcb1a expression, potentially reducing the effectiveness of the placental glucocorticoid barrier. Reference(s) [1] Mark PJ, Waddell BJ (2006) Endocrinology 147: 5147.
P1-75 Is the cortisol awakening response altered in German subjects reporting pronounced early life adversities due to World War II? P. Puetz *, T. Steffke, S. Frank, D.H. Hellhammer. University of Trier, Faculty I Psychobiology, Dep. for Theoretical and Clinical Psychobiology E-mail: [email protected] Aims: The study analyses whether there is an association between self-reported early life adversities, alterations in HPA axis activity and stress-related health impairments in the elderly. It is hypothesized that, at least in men reporting early adversities, cortisol is hypersecreted, which may coincide with depressive symptoms and a higher prevalence of hypertension, cardiovascular disease and obesity. It is explored furthermore, whether in women, on the other hand, early adversities are related to cortisol hyposecretion, dexamethasone supersuppression, pain and general fatigue. Study design: Pre- and postnatal critical life events were retrospectively assessed via questionnaire and interview. Particular emphasis was set on reported loss and severe illness of a significant other during pregnancy. Questionnaires on the medical history, psychological symptoms and reactions to stress were completed additionally. Subjects: 2900 subjects born between 1942 and 1947 in Germany were contacted and informed about the study. 350 subjects completed the questionnaire battery. Out of these, we target a sample of 150 subjects undergoing salivary cortisol sampling. Outcome measures: The salivary cortisol awakening response (0, +30, +45, +60 min) on two consecutive days and cortisol sup-
Posters
P1-70 Pain responses and fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis of infants born to opioid dependent mothers; a pilot study E.M. Hurrion *. Mater Mothers Hospital, Brisbane, Qld., Australia E-mail: [email protected]
3.5
170
2.5 2 1.5 1
Cases
0.5
Heart Rate
Cortisol (ug/dL)
3
Cases
150
Controls
Post
160 150
Cases Controls
140 130 120
0
40
20
C-M (n=12) C-F (n=14) dex-M (n=15) dex-F (n=10)
10
0
15
60
0
15
60
Minutes
Conclusions: Exposure of fetal sheep at 40 days gestation to maternal dexamethasone treatment results in a decreased hypothalamic-pituitary-adrenal response after birth in females but not males. P1-72 Adrenal gene expression in sheep is altered by maternal dexamethasone treatment in early gestation
170 Heart Rate
Cortisol (ug/dL)
1
C-M (n=12) C-F (n=14) dex-M (n=15) dex-F (n=10)
Minutes
Pre
Cases
0.5
150
0
3.5
1.5
50
200
0
120
Time Relative to Injection
Controls
60
50
130
40 min
2
Cortisol
70
250
100
Cortisol and heart rate readings at 48 h.
2.5
ACTH
300
140
Time Relative to Injection
3
Objective: To evaluate the effects of prenatal dexamethasone exposure on responses to two procedures that are conducted routinely as standard agricultural procedures in young Australian sheep. These procedures are placement of a tight rubber ligature around the base of the tail and, in males, a similar procedure to cause castration. Method: Pregnant ewes carrying singleton fetuses were randomized to control (2ml saline/ewe) or dexamethasone (dex) treatment (0.14mg/kg ewe weight) consisting of four intramuscular injections at 12-hourly intervals over 48 hours on days 40 41 (term 150 days). At 31 days of postnatal age, a rubber ring was placed around the base of the tail of each lamb, and in males, a ring was also placed around the scrotum to cause castration. Blood samples were taken from the jugular vein before commencement of the first procedure (0 minute) and 15 and 60 minutes after completion of the ring placements. ACTH and cortisol were measured by 125 I radioimmunoassay. Results: ACTH levels at 60 minutes in treatment females (dexF) were significantly lower than in treatment males (dex-M) (P = 0.006). Cortisol levels at 15 minutes in dex-F were significantly lower than in control females (C-F) (P = 0.005). At 60 minutes, cortisol levels in dex-F were lower than in control males (C-M) (P = 0.01) and treated males (dex-M) (P = 0.002). Cortisol levels in C-F were lower than in C-M (P = 0.029).
30
160
100
0
20 min
S. Li1,2 *, T.J.M. Moss1,2,4 , I. Nitsos1 , G. Polglase1,2 , T. Braun3 , J.R.G. Challis3 , J.P. Newnham1,2 . 1 School of Women’s and Infants’ Health, the University of Western Australia, WA, Australia, 2 Women and Infants Research Foundation, WA, Australia, 3 Depts of Physiology and Obstetrics and Gynecology, the University of Toronto, Canada, 4 Combined Universities Centre for Rural Health, WA, Australia E-mail: [email protected]
110
Controls Baseline
P1-71 Prenatal dexamethasone exposure results in gender-specific responses of the hypothalamic-pituitary-adrenal axis in lambs
pg/ml
Aims: To establish whether well full-term infants born to methadone (MD)/buprenorphine (bup) maintained mothers show evidence of fetal programming of HPA axis through altered baseline cortisol levels/cortisol responses to pain in the first year of life. Study design: Prospective cohort study of infants antenatally exposed to MD/bup versus comparison group of controls. Responses to routine immunisations up to 1 year were examined using heart rate and salivary cortisol levels. Subjects: Pilot study of 5 opioid-exposed infants and 4 controls. Outcome measures: Salivary cortisol levels at baseline and 20/40 minutes after painful stimulus. Heart rate at baseline and after painful stimulus. Results: After birth exposed infants have a high baseline cortisol and “downer” response to pain, with a lower baseline heart rate but also a “downer” response to pain (Fig. 1). In infancy baseline cortisol levels decline and cross over those of controls (as reported in animal model) whilst baseline heart rate is persistently lower than controls (Fig. 2). Complete 1-year data available October 2007.
controls (sample size based on this pilot data). Confirmation of pilot study findings could partly explain the recognised susceptibility of exposed individuals to ADHD, anxiety, depression and drug abuse.
ng/ml
their first prenatal visit (on average 12th week of pregnancy). As the diurnal variation in cortisol is high, only those women who gave blood before 10 a.m. were selected. This resulted in a total of 288 women for the analysis. Outcome measures: Linear regression coefficients and standard errors [SE] for continuous birth weight (grams) at term. Results: Maternal cortisol, standardized for the time of day and the pregnancy duration at blood collection, ranged from 53.77 to 291.25 mg/L and was dichotomized into low and high (>50th percentile) cortisol level. High maternal cortisol was inversely related to birth weight at term (regression coefficient [SE]: 176.89 [53.86]; P = 0.001). After adjustment for covariates (maternal age, pre-pregnancy height and BMI, education, smoking, parity, gestational age at birth, and fetal gender) high maternal cortisol was still significantly inversely related to birth weight (regression coefficient [SE]: 139.70 [47.35]; P = 0.003). Conclusions: High maternal cortisol during early pregnancy is related to lower birth weight at term.
48 hours 5-7 days 2 months 4 months 6 months 1 year
48 hours 5-7 days 2 months 4 months 6 months
Collection
Collection
Cortisol level and heart rate at baseline. CONCLUSIONS: This pilot study provides important “proof of concept” data (and first human data) to support author’s hypothesis that antenatal opioid exposure results in fetal programming of the HPA axis. A larger study is planned of 80 exposed infants & 80
S. Li1,2 *, I. Nitsos1 , G. Polglase1,2 , T. Braun3 , T.J.M. Moss1,2,4 , J.R.G. Challis3 , J.P. Newnham1,2 . 1 School of Women’s and Infants’ Health, the University of Western Australia, WA, Australia, 2 Women and Infants Research Foundation, WA, Australia, 3 Depts of Physiology and Obstetrics and Gynecology, the University of Toronto, Canada, 4 Combined Universities Centre for Rural Health, WA, Australia E-mail: [email protected] Objective: To determine if alterations in postnatal adrenal gene expression contribute to hypothalamic-pituitary-adrenal (HPA) programming resulting from maternal dexamethasone (dex) administration in early pregnancy.
Posters Method: Pregnant ewes carrying singleton fetuses were randomized to control (2 ml saline/ewe) or dexamethasone (dex) treatment (0.14 mg/kg ewe weight) consisting of four intramuscular injections at 12-hourly intervals over 48 hours on days 40 41 (term 150 days). Adrenal tissue was collected from the offspring at seven months postnatal age. Levels of mRNA of steroidogenic enzymes P450c17 and 3b hydroxysteroid dehydrogenase (3b HSD), ACTH receptor (ACTHr), glucocorticoid receptor (GR), steroidogenic acute regulatory protein (StAR), and 11b hydroxysteroid dehydrogenase 2 (11b HSD2) were determined using quantitative RT-PCR. Results: Dex-females (n = 5) had lower levels of 11b HSD2 than control females (n = 6) (P = 0.039) and dex-males (n = 7) (P = 0.042). In males, dex-treated animals had significant increases in levels of StAR (P < 0.001) and 3b HSD (P = 0.034) when compared with gendermatched controls (n = 5). ACTHr levels were similar in treated and control males and females. GR and P450c17 mRNA levels were similar across all groups. Conclusions: Maternal dexamethasone administration in early pregnancy resulted in changes in adrenal gene expression levels when measured in the offspring seven months after birth. These effects on adrenal gene expression may contribute to altered HPA responsiveness following prenatal corticosteroid exposure. P1-73 Aldosterone does not increase cell cycle activity in near-term fetal sheep cardiomyocytes S. Louey1 *, P.F. O’Tierney1 , N.N. Chattergoon1 , G.D. Giraud1,2,3,4 , K.L. Thornburg1,2,3 . 1 Heart Research Center; Departments of 2 Medicine (Cardiovascular Medicine) and 3 Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239 3098, USA, 4 Portland VA Medical Center, Portland, OR 97207 1034, USA E-mail: Email: [email protected] We have recently shown that sub-pressor doses of cortisol increase cell cycle activity in near-term fetal sheep cardiomyocytes. Cortisol acts with similar affinity via the glucocorticoid and mineralocorticoid receptors, whereas aldosterone acts exclusively via the mineralocorticoid receptor. Aims: The aim of this study was to determine the effect of aldosterone infusion on cell cycle activity in near-term fetal sheep cardiomyocytes. Study design and Subjects: Chronically instrumented fetal sheep (132d gestational age, GA; term ~145d GA) were infused with subpressor doses of aldosterone (5 mg/hr, n = 5) or vehicle (n = 5) for 48 hours. At 134d GA, fetal hearts were enzymically dissociated. Outcome measures: Isolated cardiomyocytes were analysed for size, maturational state and cell cycle activity. Data are expressed as mean±SD. Results: Aldosterone infusion increased circulating levels from 235±100 pg/ml to 1356±561 pg/ml (P < 0.05). Fetal body and heart weights were not different between the vehicle and aldosteroneinfused fetuses. Isolated cardiomyocyte size and maturational state were not different between groups. Cell cycle activity, assessed by staining for Ki-67, was not different between study groups (left ventricle: vehicle 5.6±1.4%, aldosterone 8.8±4.8%; right ventricle: vehicle 7.6±3.6%, aldosterone 6.6±3.2%). Conclusions: Forty-eight hours of aldosterone infusion did not significantly increase cell cycle activity in near-term fetal sheep cardiomyocytes, although there was a trend for increased staining for Ki-67 in the left ventricle. It is likely that increased cell cycle activity in response to cortisol infusion is mediated via the glucocorticoid receptor alone.
S103 P1-74 Placental multidrug resistance phosphoglycoprotein (ABCB1) expression is reduced by glucocorticoids during late gestation in the rat P.J. Mark *, S. Augustus, D.P. Hewitt, B.J. Waddell. School of Anatomy and Human Biology, The University of Western Australia, Perth, Western Australia 6009, Australia E-mail: [email protected] Aims: Fetal glucocorticoid excess programs adverse outcomes in adult offspring, including hypertension and insulin resistance. Access of maternal glucocorticoids to the placenta/fetus is regulated by the placental 11b-HSD enzymes, but recent studies show that glucocorticoid access to placental GR is also restricted by the multidrug resistance phosphoglycoprotein (ABCB1) [1]. However, the expression and regulation of placental ABCB1 in vivo remain poorly understood. Here we measured rat placental expression of the two ABCB1 genes (Abcb1a and Abcb1b) in normal pregnancy and following altered exposure to progesterone or glucocorticoid. Study design: Placentas were collected on days 16 and 22 of normal pregnancy and after either dexamethasone treatment (0.75 mg/ml drinking water from day 13) or ovariectomy (day 16) plus full estrogen and partial (one third) progesterone replacement. Outcome measures: Basal and labyrinth zone expression of Abcb1a and Abcb1b mRNA were determined by qRT-PCR. Results: Labyrinthine expression of both Abcb1a and Abcb1b greatly exceeded that in basal zone, and did not change significantly between days 16 and 22. Dexamethasone reduced Abcb1a only in the labyrinth zone at day 22, but had no effect on Abcb1b. Partial progesterone withdrawal had no effect on expression of Abcb1a or Abcb1b in either placental zone on day 22. Conclusions: Placental expression of Abcb1a and Abcb1b was relatively constant over the final third of rat pregnancy and was unaffected a premature reduction in progesterone. Increased glucocorticoid exposure, however, decreased labyrinthine Abcb1a expression, potentially reducing the effectiveness of the placental glucocorticoid barrier. Reference(s) [1] Mark PJ, Waddell BJ (2006) Endocrinology 147: 5147.
P1-75 Is the cortisol awakening response altered in German subjects reporting pronounced early life adversities due to World War II? P. Puetz *, T. Steffke, S. Frank, D.H. Hellhammer. University of Trier, Faculty I Psychobiology, Dep. for Theoretical and Clinical Psychobiology E-mail: [email protected] Aims: The study analyses whether there is an association between self-reported early life adversities, alterations in HPA axis activity and stress-related health impairments in the elderly. It is hypothesized that, at least in men reporting early adversities, cortisol is hypersecreted, which may coincide with depressive symptoms and a higher prevalence of hypertension, cardiovascular disease and obesity. It is explored furthermore, whether in women, on the other hand, early adversities are related to cortisol hyposecretion, dexamethasone supersuppression, pain and general fatigue. Study design: Pre- and postnatal critical life events were retrospectively assessed via questionnaire and interview. Particular emphasis was set on reported loss and severe illness of a significant other during pregnancy. Questionnaires on the medical history, psychological symptoms and reactions to stress were completed additionally. Subjects: 2900 subjects born between 1942 and 1947 in Germany were contacted and informed about the study. 350 subjects completed the questionnaire battery. Out of these, we target a sample of 150 subjects undergoing salivary cortisol sampling. Outcome measures: The salivary cortisol awakening response (0, +30, +45, +60 min) on two consecutive days and cortisol sup-