Regulation of placental growth by aldosterone and cortisol

During pregnancy, trophoblasts grow to adapt the feto-maternal unit to fetal requirements. Aldosterone and cortisol levels increase, the latter being inactivated by a healthy placenta. By contrast, preeclamptic placental growth is reduced while aldosterone levels are low and placental cortisol tissue levels are high due to improper deactivation. Aldosterone acts as a growth factor in many tissues, whereas cortisol inhibits growth. We hypothesized that in preeclampsia low aldosterone and enhanced cortisol availability might mutually affect placental growth and function. Proliferation of cultured human trophoblasts was time- and dose-dependently increased with aldosterone (P < 0.04 to P < 0.0001) and inhibited by spironolactone and glucocorticoids (P < 0.01). Mineralo- and glucocorticoid receptor expression and activation upon agonist stimulation was verified by visualization of nuclear translocation of the receptors. Functional aldosterone deficiency simulated in pregnant mice by spironolactone treatment (15 μg/g body weight/day) led to a reduced fetal umbilical blood flow (P < 0.05). In rat (P < 0.05; R(2) = 0.2055) and human (X(2) = 3.85; P = 0.0249) pregnancy, placental size was positively related to plasma aldosterone. Autocrine production of these steroid hormones was excluded functionally and via the absence of specific enzymatic transcripts for CYP11B2 and CYP11B1. In conclusion, activation of mineralocorticoid receptors by maternal aldosterone appears to be required for trophoblast growth and a normal feto-placental function. Thus, low aldosterone levels and enhanced cortisol availability may be one explanation for the reduced placental size in preeclampsia and related disorders.

Unconscious Fearful Priming Followed by a Psychosocial Stress Test Results in Higher Cortisol Levels

Human perception of stress includes an automatic pathway that processes subliminal presented stimuli below the threshold of conscious awareness. Subliminal stimuli can therefore activate the physiologic stress system. Unconscious emotional signals were shown to significantly moderate reactions and responses to subsequent stimuli, an effect called 'priming'. We hypothesized that subliminal presentation of a fearful signal during the Stroop task compared with an emotionally neutral one will prime stress reactivity in a subsequently applied psychosocial stress task, thereby yielding a significant increase in salivary cortisol. Half of 36 participants were repeatedly presented either a fearful face or a neutral one. After this, all underwent a psychosocial stress task. The fearful group showed a significant increase in cortisol levels (p = 0.022). This change was not affected by sex, age and body mass index, and it also did not change when taking resting cortisol levels into account. Post-hoc analyses showed that the increase in cortisol in the fearful group started immediately after the psychosocial stress test. Hence, subliminal exposure to a fearful signal in combination with the Stroop and followed by a psychosocial stress test leads to an increase in stress reactivity. Copyright © 2012 John Wiley & Sons, Ltd.

Variation in fat mobilization during early lactation differently affects feed intake, body condition, and lipid and glucose metabolism in high-yielding dairy cows.

Fat mobilization to meet energy requirements during early lactation is inevitable because of insufficient feed intake, but differs greatly among high-yielding dairy cows. Therefore, we studied milk production, feed intake, and body condition as well as metabolic and endocrine changes in high-yielding dairy cows to identify variable strategies in metabolic and endocrine adaptation to overcome postpartum metabolic load attributable to milk production. Cows used in this study varied in fat mobilization around calving, as classified by mean total liver fat concentrations (LFC) postpartum. German Holstein cows (n=27) were studied from dry off until d 63 postpartum in their third lactation. All cows were fed the same total mixed rations ad libitum during the dry period and lactation. Plasma concentrations of metabolites and hormones were measured in blood samples taken at d 56, 28, 15, and 5 before expected calving and at d 1 and once weekly up to d 63 postpartum. Liver biopsies were taken on d 56 and 15 before calving, and on d 1, 14, 28, and 49 postpartum to measure LFC and glycogen concentrations. Cows were grouped accordingly to mean total LFC on d 1, 14, and 28 in high, medium, and low fat-mobilizing cows. Mean LFC (±SEM) differed among groups and were 351±14, 250±10, and 159±9 mg/g of dry matter for high, medium, and low fat-mobilizing cows, respectively, whereas hepatic glycogen concentrations postpartum were the highest in low fat-mobilizing cows. Cows in the low group showed the highest dry matter intake and the least negative energy balance postpartum, but energy-corrected milk yield was similar among groups. The decrease in body weight postpartum was greatest in high fat-mobilizing cows, but the decrease in backfat thickness was greatest in medium fat-mobilizing cows. Plasma concentrations of nonesterified fatty acids and β-hydroxybutyrate were highest around calving in high fat-mobilizing cows. Plasma triglycerides were highest in the medium group and plasma cholesterol concentrations were lowest in the high group at calving. During early lactation, the decrease in plasma glucose concentrations was greatest in the high group, and plasma insulin concentrations postpartum were highest in the low group. The revised quantitative insulin sensitivity check index values decreased during the transition period and postpartum, and were highest in the medium group. Plasma cortisol concentrations during the transition period and postpartum period and plasma leptin concentrations were highest in the medium group. In conclusion, cows adapted differently to the metabolic load and used variable strategies for homeorhetic regulation of milk production. Differences in fat mobilization were part of these strategies and contributed to the individual adaptation of energy metabolism to milk production.

Cortisol levels and history of depression in acute coronary syndrome patients

BACKGROUND: Depressed mood following an acute coronary syndrome (ACS) is a risk factor for future cardiac morbidity. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is associated with depression, and may be a process through which depressive symptoms influence later cardiac health. Additionally, a history of depression predicts depressive symptoms in the weeks following ACS. The purpose of this study was to determine whether a history of depression and/or current depression are associated with the HPA axis dysregulation following ACS. METHOD: A total of 152 cardiac patients completed a structured diagnostic interview, a standardized depression questionnaire and a cortisol profile over the day, 3 weeks after an ACS. Cortisol was analysed using: the cortisol awakening response (CAR), total cortisol output estimated using the area under the curve method, and the slope of cortisol decline over the day. RESULTS: Total cortisol output was positively associated with history of depression, after adjustment for age, gender, marital status, ethnicity, smoking status, body mass index (BMI), Global Registry of Acute Cardiac Events (GRACE) risk score, days in hospital, medication with statins and antiplatelet compounds, and current depression score. Men with clinically diagnosed depression after ACS showed a blunted CAR, but the CAR was not related to a history of depression. CONCLUSIONS: Patients with a history of depression showed increased total cortisol output, but this is unlikely to be responsible for associations between depression after ACS and later cardiac morbidity. However, the blunted CAR in patients with severe depression following ACS indicates that HPA dysregulation is present.