Variation In Cortisol Concentrations Research Articles

Prenatal cortisol exposure impairs adrenal function but not glucose metabolism in adult sheep.

Adverse environmental conditions before birth are known to programme adult metabolic and endocrine phenotypes in several species. However, whether increments in fetal cortisol concentrations of the magnitude commonly seen in these conditions can cause developmental programming remains unknown. Thus, this study investigated the outcome of physiological increases in fetal cortisol concentrations on glucose-insulin dynamics and pituitary-adrenal function in adult sheep. Compared with saline treatment, intravenous fetal cortisol infusion for 5 days in late gestation did not affect birthweight but increased lamb body weight at 1-2 weeks after birth. Adult glucose dynamics, insulin sensitivity and insulin secretion were unaffected by prenatal cortisol overexposure, assessed by glucose tolerance tests, hyperinsulinaemic-euglycaemic clamps and acute insulin administration. In contrast, prenatal cortisol infusion induced adrenal hypo-responsiveness in adulthood with significantly reduced cortisol responses to insulin-induced hypoglycaemia and exogenous adrenocorticotropic hormone (ACTH) administration relative to saline treatment. The area of adrenal cortex expressed as a percentage of the total cross-sectional area of the adult adrenal gland was also lower after prenatal cortisol than saline infusion. In adulthood, basal circulating ACTH but not cortisol concentrations were significantly higher in the cortisol than saline-treated group. The results show that cortisol overexposure before birth programmes pituitary-adrenal development with consequences for adult stress responses. Physiological variations in cortisol concentrations before birth may, therefore, have an important role in determining adult phenotypical diversity and adaptability to environmental challenges.

Effects of left anodal transcranial direct current stimulation on hypothalamic–pituitary–adrenal axis activity in depression: a randomized controlled pilot trial

The main objective of this study was to evaluate the effect of left anodal transcranial direct current stimulation (tDCS) on hypothalamic–pituitary–adrenal axis (HPAA) activity in individuals with depression. We conducted a 3-week, randomized, triple-blind pilot trial with 47 participants (dropout rate: 14.89%) randomly assigned to either the tDCS or control group (sham stimulation). Salivary cortisol was used as an HPAA activity marker since cortisol is the effector hormone of the HPAA. The primary outcome was the effect of tDCS on the diurnal cortisol pattern (DCP and area under the curve with respect to ground -AUCg-). Secondary outcomes included tDCS effects on cortisol awakening response (CAR) and cortisol decline (CD), as well as the variation of cortisol concentrations between the initiation of tDCS and 2 weeks later. Intention-to-treat and per-protocol analyses were conducted. Our primary outcome showed an absent effect of tDCS on DCP and AUCg. Additionally, tDCS had an absent effect on CAR, CD, and cortisol concentration variation before-after stimulation. Our pilot study suggests that anodal tDCS showed an absent effect on HPAA activity in individuals with depression. More studies are needed to confirm these findings.

Parity-related variation in cortisol concentrations in hair during pregnancy.

ObjectiveTo investigate hair cortisol concentrations (HCC) monthly in pregnant women and to explore the effect of parity.DesignProspective cohort study from gestational week (GW) 26, at childbirth and postpartum.SettingAn antenatal care clinic in southeast Sweden.Sample390 pregnant women.MethodsCortisol was measured using radioimmunoassay in methanol extracts of ground hair samples.Main outcome measuresHair cortisol concentrations.ResultsBoth primi‐ and multiparae exhibited an increase in HCC throughout pregnancy. Primiparae had significantly higher HCC in the latter part of the last trimester compared with multiparae (1 month P = 0.003, 2 months P = 0.038). The use of psychotropic medication in the first trimester correlated to HCC postpartum (P < 0.001). HCC in GW 14–17 was associated with HCC in GW 18–21 (primiparae and multiparae, P < 0.001), GW 22–25 (primiparae P = 0.036, multiparae P = 0.033), and 2 months postpartum (primiparae P = 0.049). HCC in GW 18–21 was associated with GW 22–25 in both primiparae (P < 0.001) and multiparae (P < 0.001) as well as 2 months prior to childbirth among primiparae (<0.037). In general, all estimates of HCC in pregnancy and postpartum showed a significant association between HCC for a specific month and the HCC in the previous month (all P < 0.001), except for the association of HCC among primiparae in GW 22–25 and 3 months prior to childbirth.ConclusionsIncreased cortisol concentrations in hair were observed during pregnancy, which decreased 3 months prior to childbirth in multiparae. The results indicate a quicker suppression of the hypothalamic CRH (corticotropin‐releasing hormone) production by placenta CRH in multiparous women.Tweetable abstractMultiparae have a quicker suppression of hypothalamic CRH production by placenta CRH during pregnancy compared to primiparae.

The Value of Adrenal Androgens for Correcting Cortisol Lateralization in Adrenal Venous Sampling in Patients with Normal Cortisol Secretion.

The management of patients with adrenocorticotropic hormone-independent Cushing's syndrome and bilateral adrenal masses is challenging. Adrenal venous sampling (AVS) has been used to identify functional lesions in previous studies, but it is not always reliable. The present study aims to address the variability of cortisol in the adrenal veins of patients without excessive cortisol secretion and investigate the use of adrenal androgens to correct the cortisol lateralization ratio in AVS. Thirty-seven patients with primary aldosteronism underwent successful AVS. Patients with normal cortisol secretion exhibited a wide range of cortisol concentrations in the right (601-89, 400 nmol/l) and left (331-35, 300 nmol/l) adrenal veins. The median cortisol gradients between adrenal venous and peripheral venous samples were 15.25 and 10.14 in the right and left sides, respectively, and the cortisol lateralization ratio (high side to low side) was as high as 9.49 (median 1.54). The mean plasma levels of cortisol in the adrenal venous and peripheral venous samples decreased from t-15 to t0. Significant positive correlations were observed between the cortisol concentrations and both androstenedione and dehydroepiandrosterone concentrations in the right and left adrenal veins. After correcting for androstenedione or dehydroepiandrosterone levels, the cortisol lateralization ratio was less than 2 in most adrenal venous samples. The present study demonstrated the wide variation in cortisol concentrations in the adrenal veins of patients with normal cortisol secretion. The adrenal androgens might be ideal analytes used as normalizers when assessing the cortisol lateralization of AVS in normal or hypercortisolism cases.

Disturbance and chronic levels of cortisol in boreal woodland caribou

ABSTRACTDisturbance by anthropogenic activities may cause chronic (long‐term) stress in wildlife and contribute to population declines. Although declines of boreal woodland caribou (Rangifer tarandus caribou) across Canada have been attributed to anthropogenic disturbance, the physiological stress response of caribou to disturbance is not well understood. As a measure of chronic stress, we assessed cortisol concentrations in guard hair from 89 female caribou between 2009 and 2011 in eastern Manitoba. We compared cortisol concentrations among 5 caribou populations occupying areas with varying levels of disturbance, and estimated home ranges of 55 collared caribou to examine how home range size varied with cortisol concentrations. Within each home range, we quantified disturbance characteristics (roads, transmission lines, cottages, and logged and burned areas) and landscape features (lakes, black spruce [Picea mariana], and jack pine [Pinus banksiana]), and used model selection to determine the combination of disturbance features that best explained variation in caribou cortisol concentrations. Hair cortisol concentrations differed among the 5 caribou populations and increased with decreasing home range size. The proportion of the home range logged in the previous 6–21 years best explained variation in cortisol concentrations. Our results suggest that caribou respond negatively to logging, and caribou occupying the southern extent of their range could be vulnerable to disturbance. Although disturbance affects caribou cortisol concentrations, the consequences of increased cortisol concentrations on caribou survival and reproduction are unknown and need to be examined for effective management of populations. © 2017 The Wildlife Society.

Sources of variation in hair cortisol in wild and captive non-human primates

Hair cortisol analysis is a potentially powerful tool for evaluating adrenal function and chronic stress. However, the technique has only recently been applied widely to studies of wildlife, including primates, and there are numerous practical and technical factors that should be considered to ensure good quality data and the validity of results and conclusions. Here we report on various intrinsic and extrinsic sources of variation in hair cortisol measurements in wild and captive primates. Hair samples from both wild and captive primates revealed that age and sex can affect hair cortisol concentrations; these effects need to be controlled for when making comparisons between individual animals or populations. Hair growth rates also showed considerable inter-specific variation among a number of primate species. We describe technical limitations of hair analyses and variation in cortisol concentrations as a function of asynchronous hair growth, anatomical site of collection, and the amount and numbers of hair/s used for cortisol extraction. We discuss these sources of variation and their implications for proper study design and interpretation of results.

The cortisol awakening response predicts same morning executive function: Results from a 50-day case study

A relationship between individual differences in trait estimates of the cortisol-awakening response (CAR) and indices of executive function (EF) has been reported. However, it is difficult to determine causality from such studies. The aim of the present study was to capitalise upon state variation in both variables to seek stronger support for causality by examining daily co-variation. A 50 days researcher–participant case study was employed, ensuring careful adherence to the sampling protocol. A 24-year-old healthy male collected saliva samples and completed an attention-switching index of EF on the morning of each study day. Subsidiary control measures included wake time, sleep duration, morning fatigue, and amount of prior day exercise and alcohol consumption. As the CAR preceded daily measurement of EF, we hypothesised that, over time, a greater than average CAR would predict better than average EF. This was confirmed by mixed regression modelling of variation in cortisol concentrations, which indicated that the greater the increase in cortisol concentrations from 0 to 30 min post-awakening (CAR) the better was subsequent EF performance at 45 min post-awakening (t = 2.29, p = 0.024). This effect was independent of all potential confounding measures. Results are discussed in terms of implications for the understanding of the relationship between the CAR and the cognitive function, and the previously suggested role of the CAR in “boosting” an individual’s performance for the day ahead.

Assessing HPA feedback sensitivity without pharmacological interventions? On the distribution of cortisol concentrations in phases of varying secretory activity

TheCortisolAwakeningResponse (CAR)has risen toprominence in recent years as a predictor of both physical and psychological health status. However, the role of the CAR within the healthy circadian rhythmremains speculative; previously described asproviding an unspecified ‘boost’ for the day ahead. Recent studies have demonstrated a positive relationship between the CAR and Executive Function (EF) in samples of older adults and in cases of abnormal cognitive function. The aim of the present research was to explore the relationship between the CAR and an attention switching index of EF in a healthy young adult. It was hypothesised that a larger CAR would predict better attention switching task (AST) performance on the same morning. This was assessed using a researcher-participant case-study of a healthy 24-year old male (RL) across 50 days. Cortisol sampling (nested within days) was at 15-min intervals across the post-awakening hour. AST performance was assessed at 45-min post-awakening. Mixed regression modelling of variation in cortisol concentrations confirmed that the greater the increase in cortisol concentrations from 0–30min post-awakening (CAR) the betterwas subsequent AST performance at 45min post-awakening (t=2.29, p= .024). This effect was independent of awakening time and other potential confounds. These findings suggest that state variation in the CAR predicts state variation in performance on this index of EF post-CAR, and if replicated in further samples of healthy adults, may indicate a mechanism by which the CARmodulates cognitive performance for the day ahead.

Aggression and cortisol levels in three different group housing routines for lactating sows.

BackgroundLactating sows in Swedish organic piglet production are commonly group-housed with piglets in a multi-suckling pen within 14 days after farrowing. Nursing behaviour may be disturbed when lactating sows are moved to a new environment and mixed with other sows, as they spend more time fighting with other sows and exploring the new surroundings. This can disrupt the inhibitory effect of suckling on ovarian activity and increase the risk of lactational oestrus, making efficient reproductive management difficult. Therefore this study evaluated aggression and levels of the stress hormone cortisol in lactating sows group-housed together with their piglets at one (W1), two (W2) or three (W3) weeks post farrowing.ResultsThere was no significant difference (P > 0.05) between the three management routines (W1, W2, W3) regarding number of attacks initiated or received in the mixed group. After mixing, W2 sows had a lower number of shoulder scratches (P < 0.05) than W3 sows. Among the W3 sows, there was a lower (P < 0.01) cortisol concentration in saliva when sows were group housed compared to when they were individually housed. The cortisol response, measured as variation in cortisol concentration in saliva, was also lower (P < 0.05) in group-housed W3 sows compared with W1 sows.For all management routines, sows already living in the new environment (resident sows) initiated more attacks (P < 0.001) and received fewer attacks (P < 0.01) than sows entering the new environment (intruder sows). Overall, multiparous sows initiated more attacks and received fewer attacks than primiparous sows (P <0.001).ConclusionsOverall, the results suggest that mixing and group housing sows at three weeks post farrowing is less stressful than mixing and group housing sows at one week post farrowing. The results also indicate that parity and whether a sow is a resident or intruder in the group housing environment may have an effect on aggression levels when sows are group-housed.

Redtail and red colobus monkeys show intersite urinary cortisol concentration variation in Kibale National Park, Uganda.

Non-invasive measurement of urinary cortisol is a proven method of evaluating the impact of environmental stressors on wild primates. Variation in cortisol concentrations can reflect physiological stress, and prolonged elevation of circulating cortisol can significantly affect individual and population-level health. In a previous study, we found that urinary cortisol concentrations in grey-cheeked mangabeys (Lophocebus albigena) were higher at a highly disturbed site (Mainaro) in Kibale National Park, Uganda compared with a minimally disturbed site (Ngogo) in the same habitat. Here, we expand on this research, reporting on cortisol concentrations in two other cercopithecid monkeys (Cercopithecus ascanius and Piliocolobus rufomitratus) at the same two sites. We hypothesized that C. ascanius would show no difference between sites, given its preference for secondary forests, while P. rufomitratus would have higher cortisol concentrations at the disturbed site. Contrary to expectations, both species exhibited significantly higher cortisol concentrations at Ngogo (minimally disturbed) compared with Mainaro (disturbed). We suggest that these results may be caused by inter- or intragroup social dynamics, intersite differences in predation rate, fruit/food availability and chemistry, or a combination of these factors. These initial evaluations of urinary cortisol concentrations provide testable hypotheses on habitat disturbance and Kibale primate ecophysiology.

Developing a new research tool for use in free-ranging cetaceans: recovering cortisol from harbour porpoise skin.

We developed a chemical analytical procedure for sampling, extracting and determining epidermal skin cortisol concentrations (SCCs) in the harbour porpoise (Phocoena phocoena) using gas chromatography-tandem mass spectrometry. In brief, this involved a pressurized liquid extraction with a two-step solid-phase clean-up. A derivatization step was conducted prior to detection. To evaluate the new assay, cortisol was analysed in three different sample types obtained from four harbour porpoises: skin plates, dorsal fin skin plugs (with and without lidocaine) and epidermal scrapes. Skin cortisol concentrations could be measured using the new assay in the majority of the tested skin samples down to a minimal sample size of 49 mg dry weight (dw). Water content ranged from 10 to 46% in the plug samples, which had SCCs from 2.1 to 77.7 ng/g dw. Epidermal scrape samples had the highest water content (83-87%) and lower SCCs (0.6-15 ng/g dw), while the skin plates had intermediate water contents (60-66%) and SCCs of 2.6-13.0 ng/g dw. SCC was slightly higher in plugs with lidocaine than without (average values of 41 and 33 ng/g dw, respectively). Substantial within-individual variations in cortisol concentrations are also common in other matrices such as blood and hair. Some important factors behind this variation could be e.g. the animal's sex, age, body condition, reproductive stage, and the body region sampled, as well as season, moulting cycles and water temperature. Clearly, more research into SCCs is required. The findings described here represent the first critical steps towards using epidermal skin cell samples to assess chronic stress levels in cetaceans and the development of a widely applicable health-assessment tool in these species.

Time lag between peak concentrations of plasma and salivary cortisol following a stressful procedure in dairy cattle.

BackgroundMeasurement of salivary cortisol has been used extensively as a non-invasive alternative to blood sampling to assess adrenal activity in ruminants. However, there is evidence suggesting a considerable delay in the transfer of cortisol from plasma into saliva. Previous studies in cattle have used long sampling intervals making it difficult to characterise the relationship between plasma and salivary cortisol (PLCort and SACort, respectively) concentrations at different time points and determine whether or not such a time lag exist in large ruminants. Therefore, the objective of this study was to characterise the relationship between plasma and salivary cortisol and determine if there is a significant time lag between reaching peak cortisol concentrations in plasma and saliva across a 4.25 h time-period, using short sampling intervals of 10–15 min, following social separation in dairy cattle.Five cows were separated from their calves at 4 days after calving, and six calves were separated from a group of four peers at 8 weeks of age. Following separation, the animals were moved to an unfamiliar surrounding where they could not see their calves or pen mates. The animals were catheterised with indwelling jugular catheters 1 day before sampling. Blood and saliva samples were obtained simultaneously before and after separation.ResultsIn response to the stressors, PLCort and SACort increased reaching peak concentrations 10 and 20 min after separation, respectively. This suggested a 10 min time lag between peak cortisol concentrations in plasma and saliva, which was further confirmed with a time-series analysis. Considering the 10 min time lag, SACort was strongly correlated with PLCort (P < 0.0001).ConclusionsSalivary cortisol correlates well with plasma cortisol and is a good indicator of the time-dependent variations in cortisol concentrations in plasma following acute stress. However, there is a time lag to reach peak cortisol concentrations in saliva compared to those in plasma, which should be considered when saliva samples are used as the only measure of hypothalamic-pituitary-adrenal axis response to stress in cattle.

Plasma cortisol concentration increases within 6 hours of stabling inRAO‐affected horses

In many inflammatory diseases plasma cortisol concentration (CORT) increases at the onset of acute inflammation, but the situation in recurrent airway obstruction (RAO) of horses is unknown. Split-plot repeated measures design with one grouping factor (disease) and two repeated factors (day and 3-hour intervals). To test the hypothesis that CORT increases as acute exacerbations of RAO develop. Four RAO-susceptible and 4 control horses were placed in a low dust environment (LDEnv) for 2 days followed by 2 days in a high dust environment (HDEnv). Exacerbations of RAO were indicated by increases in maximal change in pleural pressure (ΔPplmax) and decreases in breathing frequency variability (BFV), which was continuously measured by respiratory inductance plethysmography. Plasma samples for determination of CORT were collected every 6 h. In control horses, ΔPplmax and BFV were unaffected by the HDEnv, whereas in RAO-affected horses ΔPplmax increased and BFV decreased significantly. In the LDEnv, there was a circadian variation in CORT in both control and RAO-affected horses. In HDEnv, CORT was unaffected in control horses, but increased significantly in RAO-affected horses between 6 and 12 h after entering the HDEnv. Plasma cortisol concentration increases concurrently with the development of acute exacerbations of RAO.

Work hours and cortisol variation from non-working to working days

This study aims at modelling the relationship between the number of work hours per week and cortisol variation across 3days by comparing non-working day to working day in a population of day-shift workers. Questionnaire data and saliva samples for cortisol analysis were collected on 132day-shift workers employed in 13 workplaces in Canada. Consenting workers provided 5 saliva samples a day (awaking, 30min after awaking, 2p.m., 4p.m., bedtime) repeated 3 times (Saturday, Tuesday, Thursday) over a week, to provide measures at work and non-work times and settings. Multilevel regression models were estimated from cortisol measurements at each occasion within a day at level-1, days at level-2 and workers at level-3. Controlling for gender and age, results revealed significant variations in salivary cortisol concentration between sample, day and worker levels. Cortisol increases linearly from non-working day to work days and work hours per week interacted with days, revealing a positive association between the number of work hours per week and cortisol concentrations during these days. Work hours per week did not interact with awaking, 30min after awaking, 2p.m., 4p.m., and bedtime cortisol concentrations. Gender and age had neither main effects nor interaction effects. No significant cortisol variations were found between workplaces. These results suggest that work hours act as a stressor that is associated with significant variations in cortisol concentrations over working days. Non-working days may contribute to stress reduction in workers who experience longer work hours.

Circadian and circannual rhythms of cortisol, ACTH, and α-melanocyte-stimulating hormone in healthy horses

Cosinor analysis was used to evaluate whether pituitary and adrenal hormones exhibit circadian rhythmicity in horses. The effect of season and animal age on their respective rhythms was also determined. In addition, the usefulness of evaluating cortisol rhythmicity for the diagnosis of pituitary pars intermedia dysfunction (PPID) was assessed. Serum cortisol concentrations (P < 0.01), but not plasma ACTH or α-melanocyte-stimulating hormone (α-MSH), showed a significant circadian periodicity in horses. An effect of season on hormone concentration was observed with plasma ACTH and α-MSH concentration greater in the fall and cortisol concentration greater in the spring (P < 0.001). Age did not affect cortisol rhythm, but it did blunt the variation in cortisol concentration in horses, similar to what has been previously reported to occur in aged people and dogs. In addition, our results suggest that clinically and diagnostically normal, non–PPID-affected horses commonly have a loss of cortisol diurnal rhythm. Therefore, measurement of circadian rhythm is not an appropriate diagnostic test for PPID.

Assessment of adrenocortical function in the critically ill

To review current concepts in the diagnosis of adrenocortical disease in the critically ill patient.A review of articles reported on adrenocortical insufficiency in the acutely ill patient.The contribution of adrenal insufficiency to the morbidity of critically ill patients is currently under renewed scrutiny. The debate continues about the role of steroids in sepsis and essentially the question remains unanswered. Central to this debate is the issue of whether adrenal insufficiency is common in the critically ill patient. What is incontrovertible is that adrenocortical function is essential for host survival during critical illness, but what constitutes adrenocortical insufficiency in critically ill patients is not clear. Absolute adrenocortical insufficiency (diagnosed by very low plasma cortisol concentrations) is uncommon in the intensive care population. The diagnosis of relative adrenocortical insufficiency (elevated basal plasma cortisol with a subnormal increase in plasma concentrations following an ACTH stimulus) continues to generate debate. The controversy surrounding the role of steroids in sepsis and the confusion over the criteria for diagnosing adrenal insufficiency in the critically ill are reviewed.We suggest that the following caveats be borne in mind when diagnosing adrenal insufficiency in the critically ill patient. Firstly, the gold standard for the diagnosis has not been established. Secondly, caution must be exercised when interpreting a single plasma cortisol value. In the event of a single result indicating adrenal hypofunction, we suggest repeating the measurements after a 6 to 12 hour interval. The clinician must also be aware of variations in cortisol concentrations induced by the assay. Thirdly, the clinician must be aware of the potential limitations of the conventional high dose corticotrophin test. We also suggest that plasma free cortisol is more relevant than total plasma cortisol in the assessment of adrenal function in critical illness and that the low dose corticotrophin test is more sensitive than the conventional high dose test. These areas should be the subject of further investigations.

Organochlorines Affect the Steroid Hormone Cortisol in Free-Ranging Polar Bears (Ursus maritimus) at Svalbard, Norway

Since the polar bear (Ursus maritimus) is among the most highly organochlorine-contaminated species of the Arctic mammals, there is growing concern that in addition to the natural stressors in the polar bear's environment, several organochlorines (OCs) may be able to change basic endocrine pathways. Alterations in the hypothalamic–pituitary–adrenal (HPA) axis may affect plasma cortisol concentrations and inhibit physiological processes involved in the maintenance of homeostasis in a way that may endanger the animal's health. Between 1995 and 1998, samples were collected from 121 male and 130 female free-ranging polar bears from the Svalbard area. The aim of the study was to investigate relationships between plasma cortisol concentrations, biological factors, and OCs. The variation in plasma cortisol concentrations was determined for the total sample. Axillary girth and body mass together with their interactions explained more than 50% of the variation in the plasma cortisol concentration. The sum of pesticides (Σpesticides) combined with the sum of polychlorinated biphenyls (ΣPCBs) and their interactions explained over 25% of the variation in the cortisol concentration. Although Σpesticides contributed negatively and ΣPCBs contributed positively to the variation in the plasma cortisol, the over-all contribution of the OCs to the plasma cortisol variation was negative. Despite the complexity on stress responses and the interactions with environmental factors, this study demonstrated that high concentrations of OCs in polar bears might alter plasma cortisol concentrations.

When is fasting really fasting? The influence of time of day, interval after a meal, and maternal body mass on maternal glycemia in gestational diabetes

Objective: The object of the study was to determine whether time of day, interval after a standard meal, and maternal body mass influence plasma glucose concentrations in women with gestational diabetes mellitus. Study Design: Identical mixed meals were administered on 2 separate occasions 1 week apart to 30 women with dietarily treated gestational diabetes and pregnancies between 28 and 38 weeks’ gestation. One meal was administered at 7 AM (morning meal) and the other was administered at 9 PM (evening meal), each after a fast of ≥5 hours. The order of the meals (morning first versus evening first) was assigned randomly. Sixteen of the women had a body mass index ≥27 kg/m 2 (overweight) and 14 women had a body mass index <27 kg/m 2 (lean). Venous plasma concentrations of glucose, insulin, free fatty acids, β-hydroxybutyrate, and bound and free cortisol were measured hourly for 9 hours after each of the test meals. Results: When all women were considered together glucose concentrations after the morning meal were significantly greater at 1 hour, were not different at 2 hours, and were significantly lower from 3 through 9 hours postprandially than those at corresponding times after the evening meal. Plasma β-hydroxybutyrate and free fatty acid concentrations were higher between 5 and 9 hours after the morning meal than at the same times after the evening meal. Total and free cortisol levels were higher for the first 7 hours after the morning feeding, reflecting known diurnal variation in cortisol concentrations. Overweight patients’ glucose values were significantly greater than those of lean subjects during the last 4 hours of the overnight fast. Conclusions: Among women with dietarily treated gestational diabetes the glucose concentrations were significantly higher from 3 to 9 hours after an evening meal, whereas suppression of free fatty acids and β-hydroxybutyrate was less sustained after a morning feeding. The mechanisms underlying these differences remain to be determined but may involve diurnal influences of counterregulatory hormones. The relationships between measurements of maternal glycemia and maternal and perinatal outcomes in pregnancies complicated by gestational diabetes may be clarified by establishing a uniform duration of a fast and by developing meal-specific preprandial and postprandial maternal glucose targets for these patients. (Am J Obstet Gynecol 1999;181:904-11.)

Hormonal and immunological changes in blood and mammary secretion in the sow at parturition

The purpose of the present study was to record possible variations of estradiol-17β (E2) and cortisol concentrations, and parameters related to granulocyte phagocytosis in mammary secretions from healthy sows at parturition. The study was comprised 8 primiparous sows (Landrace x Yorkshire). Blood and mammary secretion samples were collected twice daily from 3 d before (only blood) until 3 d after farrowing. Estradiol-17β and cortisol concentrations were determined in plasma and in cell-depleted skimmed mammary secretions. Phagocytic capacity of polymorphonuclear cells (PMN) was assessed in whole blood and in cell suspensions derived from mammary secretions. Opsonic activity was assessed in serum and in cell-depleted skimmed mammary secretions. The 2 assays were based on chemiluminescence. Estradiol-17β concentration in plasma decreased (P<0.001) directly after parturition. In skimmed secretions, the highest E2 concentration was recorded in the first sample after parturition and decreased (P<0.01) thereafter. The highest cortisol concentration in plasma was recorded in the evening before parturition (P<0.01). In skimmed secretions, there was no significant variation in cortisol concentration. The concentrations of both steroid hormones were lower in mammary secretions than in plasma. The phagocytic capacity of PMN in blood and mammary secretion, expressed as peak chemiluminescence per PMN, showed no significant change. This was also true for the opsonic activity in serum. In skimmed secretions the opsonic activity increased (P<0.01) after parturition. These data emphasize the differences between plasma and mammary secretion concentrations of steroid hormones as well as between systemic and mammary gland immune competence. Regarding the phagocytosis process in mammary secretions, the part directly related to the PMN function seemed not to be altered at parturition compared with later on in lactation, whereas the part related to opsonic activity seemed to be impaired at parturition. The latter may play a role in the development of coliform mastitis at this time.

Metabolic effects of the nocturnal rise in cortisol on carbohydrate metabolism in normal humans.

Glucocorticoid concentrations vary throughout the day. To determine whether an increase in cortisol similar to that present during sleep is of physiologic significance in humans, we studied the disposition of a mixed meal when the nocturnal rise in cortisol was mimicked or prevented using metyrapone plus either a variable or constant hydrocortisone infusion. When glucose concentrations were matched with a glucose infusion, hepatic glucose release (2.6 +/- 0.2 vs. 1.5 +/- 0.4 nmol/kg per 6 h) was higher (P < 0.05) while glucose disappearance (5.9 +/- 0.3 vs. 7.3 +/- 0.9 mmol/kg per 6 h) and forearm arteriovenous glucose difference (64 +/- 24 vs. 231 +/- 62 mmol/dl per 6 h) were lower (P < 0.05) during the variable than basal infusion. The greater hepatic response during the variable cortisol infusion was mediated (at least in part) by inhibition of insulin and stimulation of glucagon secretion as reflected by lower (P < 0.05) C-peptide (0.29 +/- 0.01 vs. 0.38 +/- 0.04 mmol/liter per 6 h) and higher (P < 0.05) glucagon (42.7 +/- 2.0 vs. 39.3 +/- 1.8 ng/ml per 6 h) concentrations. In contrast, the decreased rates of glucose uptake appeared to result from a state of "physiologic" insulin resistance. The variable cortisol infusion also increased (P < 0.05) postprandial palmitate appearance as well as palmitate, beta-hydroxybutyrate, and alanine concentrations, suggesting stimulation of lipolysis, ketogenesis, and proteolysis. We conclude that the circadian variation in cortisol concentration is of physiologic significance in normal humans.