Relationships of urinary adrenal steroids at age 8 years with birth weight, postnatal growth, blood pressure, and glucose metabolism

INTRODUCTION: Overactivity of the hypothalamic-pituitary-adrenal axis through a program set by early growth patterns is hypothesized to lead to central obesity, insulin resistance, and hypertension. We therefore examined links between adrenal steroid production and birth weight, rapid early growth, and body mass index (BMI), blood pressure, waist circumference, and resistance to insulin in early childhood through the action of adrenal steroids. METHODS: Timed overnight urine samples were collected in 461 children from a large representative birth cohort. In total 244 boys and 188 girls aged 8.2-8.4 yr completed the protocol. The excretion rates of individual steroids were measured to determine total androgen and cortisol metabolites. Indices of activity of 5alpha-androgen reduction of androgens and cortisol metabolites and 11beta-hydroxy steroid dehydrogenase activity were calculated. RESULTS: In both boys and girls, total urinary androgen and cortisol metabolites were positively related to current height, weight, BMI, and waist circumference. Girls had higher urine androgen metabolite levels and 5alpha-androgen indexes than boys, and in girls higher androgen metabolite excretion was associated with lower birth weight and faster postnatal weight gain. After adjustment for current BMI, total cortisol metabolites and 11beta-hydroxy steroid dehydrogenase index were not related to birth weight or postnatal weight gain in either sex. CONCLUSIONS: These data confirm early growth associations in this cohort seen with plasma levels of adrenal androgens at age 8 yr, at least in girls. Larger studies and follow-up during puberty are needed to exclude the possibility of programming of cortisol metabolism by early growth.     

Prolonged psychological stress suppresses cortisol secretion

OBJECTIVE: Response to acute psychological stress is characterized by activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. However, response to the prolonged psychological stress is less well known. DESIGN: This study was designed as a prospective assessment of cortisol secretion during prolonged psychological stress induced by continuous air raids and after elimination of the stress-inducing factor. SUBJECTS: The study group consisted of five healthy subjects (34-39 years). MEASUREMENTS: Psychological and endocrine (morning cortisol and 1 microg ACTH test) testing was done 2 months after the war had begun and 18 months after the end of it. Psychiatric assessment was done at the same periods, and 30 months after the start of the study. RESULTS: After 2.5 years of follow-up, there were no signs of endocrine or psychiatric disorders in any of the subjects. After the war, Beck Inventory of Depression and Hamilton Anxiety Rating Scale scores were significantly reduced. Suppression of the HPA axis was present during the war but not after. CONCLUSIONS: Prolonged psychological stress is associated with a transient suppression of the HPA axis, manifested by low morning cortisol and reduced cortisol response to ACTH. The reduction of cortisol response is sufficient to cause false diagnosis of HPA insufficiency.     

Infant stress reactivity and prenatal alcohol exposure

BACKGROUND: Animal studies have shown that prenatal alcohol exposure (PAE) is linked to alterations in the stress response systems. To date, little is known about the impact of PAE on stress systems in human infants. The current study examined PAE effects on the stress response, as evidenced by the activation of the limbic-hypothalamic-pituitary-adrenal (L-HPA) axis and autonomic system and changes in negative affect during a social-emotional challenge in human infants. We also examined whether the effects of PAE on infant responsiveness differed in boys and girls. METHODS: Measures of cortisol, heart rate, and negative affect were obtained during a modified version of Tronick's still-face procedure, a standardized developmental paradigm used to study emotion and stress regulation. Our sample included fifty-five 5- to 7-month-old infants whose mothers were enrolled in an alcohol intervention study. Measures of maternal alcohol consumption during pregnancy and after delivery were obtained using Timeline Followback interviewing methods. Relationships between prenatal alcohol consumption and infant outcomes were examined. In addition, mothers were divided into high and low-frequency drinkers, based on the mean percent of prenatal drinking days (PDD) to facilitate between-group comparisons of infant stress measures. RESULTS: Mothers enrolled in our study reported significant reductions in alcohol consumption after learning of their pregnancies. Nevertheless, PDD from conception to pregnancy recognition was related to increases in cortisol reactivity, elevated heart rate, and negative affect in their infants. The effects of PAE on infant responsiveness were significant after controlling for the effects of maternal depression and annual income. In addition, the effects of PAE on cortisol reactivity differed for boys and girls. CONCLUSIONS: Greater PAE was related to greater activation of stress response systems. Our findings suggest that PAE affects the development of infant stress systems and that these effects differ in boys and girls. This work supports the possibility that PAE is related to alterations in infant stress systems, which could underlie problems in cognitive and social-emotional functioning that are common among persons exposed prenatally to alcohol.     

Rise in morning saliva cortisol is associated with abdominal obesity in men: a preliminary report

An abnormal regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with risk factors for cardiovascular disease and Type 2 diabetes mellitus. The objective of this study was to examine if morning saliva cortisols show similar associations. Twenty-eight men, all 53 yr of age, delivered during an ordinary working day saliva cortisol samples immediately upon awakening and 15 min thereafter as well as at different times during the day, including after a standardized lunch. Dexamethasone (0.5 mg) suppression of cortisol was also measured. The rise of morning cortisol values was positively associated with body mass index (r: 0.45, p=0.016), waist/hip ratio (r: 0.54, p=0.003), abdominal sagittal diameter (r: 0.54, p=0.003), glucose (r: 0.54, p=0.003), insulin (r: 0.57, p=0.002) and triglycerides (r: 0.46, p=0.014). The morning rise also correlated positively with the elevation of cortisol following lunch (r: 0.45, p=0.043) but not with other cortisol measurements or dexamethasone suppression. Elevation of cortisol immediately after awakening has previously been found to provide a simple indicator of HPA axis regulation, as suggested also by the results of this study, and an elevated rise has been reported after exposure to frequent or chronic perceived stress. The rise of cortisol immediately after awakening might be an indicator of an increased risk of developing serious, prevalent diseases via the metabolic syndrome.     

Size at birth, the metabolic syndrome and 24-h salivary cortisol profile

OBJECTIVE: Individual variation in hypothalamic-pituitary-adrenal axis (HPAA) function has been suggested to be important in linking small size at birth with adult cardiovascular disease and its risk factors, in particular the metabolic syndrome. Human studies have, however, so far only been performed in clinic settings, and their results have not been consistent. Our aim was to assess whether HPAA activity in everyday living circumstances is related to the metabolic syndrome and size at birth. DESIGN: Clinical birth cohort study. SUBJECTS: A total of 151 women born between 1924 and 1933 in Helsinki, Finland, with measurements at birth recorded. The subjects had previously undergone detailed clinical examinations including fasting cortisol measurement and 1 micro g ACTH1-24 and overnight 0.25 mg dexamethasone tests. MEASUREMENTS: Salivary cortisol concentration was measured during a normal 24-h period: at awakening, 15 and 30 min thereafter, at 12.00 h, 17.00 h and 22.00 h and the following morning. In addition, the following summary variables were calculated: awakening response (mean of the three awakening measurements), mean of all individual measurements, and mean, SD and contrast (a measure of blunted diurnal variability, calculated as mean of morning minus mean of 1200, 1700 and 2200) of all individual z scores. RESULTS: Salivary cortisol awakening response was correlated with serum fasting (r = 0.17; P = 0.04), ACTH1-24-stimulated (r = 0.32; P < 0.0001), and dexamethasone-suppressed (r = 0.29; P = 0.0004) cortisol concentrations. However, no salivary cortisol measurement was associated with any component of the metabolic syndrome (waist circumference, serum triglyceride, HDL cholesterol or glucose concentration, or blood pressure). Moreover, no correlation was observed between salivary cortisol and weight, length, ponderal index, or gestational age at birth. CONCLUSIONS: In elderly women, cortisol concentrations in an everyday environment do not appear to be associated with the metabolic syndrome or size at birth. We propose that detecting relationships between HPAA function, prenatal events and adult disease might require a test involving HPAA stimulation.     

Cortisol secretary pattern and glucocorticoid feedback sensitivity in women from a Mediterranean area: relationship with anthropometric characteristics, dietary intake and plasma fatty acid profile

BACKGROUND: Chronic stress is associated with a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis consisting on disturbances on the cortisol response and lipid metabolism. OBJECTIVE: To evaluate the HPA axis activity in women from a Mediterranean area, comparing three different measurements: daily cortisol secretory variability, postprandial cortisol secretion and glucocorticoid feedback sensitivity. In addition, HPA axis disturbance is correlated with dietary habits and plasma fatty acid profiles. DESIGN: The participants were 41 women born during the first 6 months of 1960 and living in a Mediterranean area (Murcia, Spain). They were of normal weight, with a waist circumference of 80.5 +/- 9.3 cm. Their salivary cortisol levels, 7-day dietary record and plasma fatty acid profile were evaluated. Daily cortisol variability and postlunch cortisol secretion were recorded and a dexamethasone suppression test is performed in order to detect possible HPA disturbance. RESULTS: Both the methods used for HPA axis evaluation were positively correlated (r = 0.448, P = 0.004). Subjects with normal diurnal curves (high cortisol variability) showed significantly higher cortisol values in the morning and postprandial cortisol secretion than women with pathological curves (medium and low variability). Cortisol variability was inversely correlated with waist circumference (r = -0.312, P = 0.047), suggesting that a disturbed HPA axis response may lead to an android pattern of body fat distribution. Dietary fat and saturated fatty acid intake were lower in the high cortisol variability group, while monounsaturated fatty acid intake was higher (P < 0.05). No major differences were reported in plasma fatty acid profile. CONCLUSIONS: A disturbed HPA axis is associated with abdominal fat distribution and a higher content of fat and saturated fatty acids in the diet. Women who chose a dietary pattern closer to the Mediterranean diet, with high monounsaturated fatty acid intake, showed lower levels on HPA axis disturbance.     

Obesity and the hypothalamic-pituitary-adrenal axis in adolescent girls

Stress and stress-related concomitants, including hypothalamic-pituitary-adrenal (HPA) axis activation, are implicated in obesity and its attendant comorbidities. Little is known about this relationship in adolescents. To begin to address this important knowledge gap, we studied HPA axis activity in 262 healthy adolescent girls aged 11, 13, 15, and 17 years. We hypothesized that obesity would be correlated with increased HPA axis activity and reactivity. Measures of HPA axis activity included 3 blood samples obtained midday (between 1:00 and 2:00 pm) over the course of 40 minutes; overnight urine free cortisol; and cortisol levels 0, 20, and 40 minutes after venipuncture (cortisol reactivity). Measures of adiposity included body mass index (BMI), BMI z score (BMI-Z), percentage body fat, and fat distribution (central adiposity) assessed by dual-energy x-ray absorptiometry. Daytime levels of serum cortisol were inversely associated with BMI-Z and central adiposity (P < .05). The urine free cortisol excretion rate was positively correlated with BMI, BMI-Z, and central adiposity. There was blunting of cortisol response to venipuncture with increasing adiposity. Our results suggest that there may be reduced cortisol levels during the day and increased levels at night with increasing degree of adiposity. This study provides preliminary findings indicating an alteration of the circadian rhythm of cortisol with obesity. We conclude that obesity is associated with altered HPA activity in adolescent girls. The clinical implications of our findings require further investigation.     

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

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 ACTH1-24 -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 ACTH1-24 stimulation were similar for participants exposed to famine during late, mid- or early gestation (P = 0.78). Cortisol concentrations after dexamethasone suppression test did not differ between those exposed and those unexposed to famine in utero (mean difference -2% (95% confidence interval (CI) -27 to 23)). Neither peak cortisol concentration (20 nmol/l (95% CI -27 to 66)), cortisol increment (-5 nmol/l (95% CI -56 to 47)) or cortisol area under the curve post-ACTH1-24 injection (4% (95% CI -4 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.     

Hair cortisol as a marker of hypothalamic-pituitary-adrenal Axis activity in female patients with major depressive disorder

Metabolic Brain Disease - Hair cortisol is regarded as a promising marker of hypothalamic-pituitary-adrenal axis (HPAA) activity alterations due to stress, somatic and mental health conditions....     

Reduced hypothalamic-pituitary and sympathoadrenal responses to hypoglycemia in women with fibromyalgia syndrome.

PURPOSE: To perform a detailed comparison of the hypothalamic-pituitary-adrenal axis and the sympathoadrenal system in women with and without fibromyalgia. SUBJECTS AND METHODS: Fifteen premenopausal women who met the 1990 American College of Rheumatology criteria for the diagnosis of fibromyalgia and 13 healthy, premenopausal women were enrolled. We measured baseline 24-hour urinary free cortisol levels and evening and morning adrenocorticotropic hormone (ACTH) and cortisol levels, performed stepped hypoglycemic hyperinsulinemic clamp studies in which serum glucose levels were decreased from 5.0 to 2.2 mmol/L, and compared the effects of infusions of placebo and ACTH. RESULTS: Women with fibromyalgia had normal 24-hour urinary free cortisol levels and normal diurnal patterns of ACTH and cortisol. There was a significant, approximately 30%, reduction in the ACTH and epinephrine responses to hypoglycemia in women with fibromyalgia compared with controls. Prolactin, norepinephrine, cortisol, and dehydroepiandrosterone responses to hypoglycemia were similar in the two study groups. In subjects with fibromyalgia, the epinephrine response to hypoglycemia correlated (P = 0.01) inversely with overall health status as measured by the fibromyalgia impact questionnaire. Graded ACTH infusion revealed similar increases in cortisol in women with fibromyalgia and healthy controls. CONCLUSIONS: Patients with fibromyalgia have an impaired ability to activate the hypothalamic-pituitary portion of the hypothalamic-pituitary-adrenal axis as well as the sympathoadrenal system, leading to reduced ACTH and epinephrine responses to hypoglycemia.     

Does birth weight predict adult serum cortisol concentrations? Twenty-four-hour profiles in the United kingdom 1920-1930 Hertfordshire Birth Cohort

Low birth weight and weight in infancy are associated with adult insulin resistance and type 2 diabetes. A proposed mechanism is programming of the hypothalamic-pituitary-adrenal axis by intrauterine undernutrition, leading to persistently elevated cortisol concentrations. We examined 24-h serum cortisol profiles (samples every 20 min) in 83 healthy elderly men and women whose birth weight and infant weight were recorded. Variables derived from these profiles included trough, peak, and area under the curve concentrations; the time of onset, rate of rise, duration, and peak of the early morning cortisol rise; postprandial secretion; and regularity of secretion (approximate entropy). None of these parameters was related to birth weight, weight at 1 yr, or change in weight SD score between birth and 1 yr. Consistent with other studies, 0730-0900 h cortisol concentrations were higher in men and women of lower birth weight, although this was not statistically significant (P = 0.08). Our findings do not support the hypothesis that reduced intrauterine and infant growth are associated with continuously raised cortisol concentrations in old age. Programmed effects on the hypothalamic-pituitary-adrenal axis may influence reactivity rather than resting secretion.     

Circadian rhythm of adrenergic regulation of adrenocorticotropin and cortisol secretion in man

The effects of the alpha-adrenergic agonist methoxamine on the human hypothalamic-pituitary-adrenal axis was assessed by a placebo-controlled study in the morning and one in the evening. A 5-mg iv bolus dose of methoxamine in normal subjects caused a significant rise in plasma ACTH and cortisol concentrations in the morning study. However, no significant change in plasma cortisol or ACTH concentrations was noted during the evening study. These studies suggest the existence of a diurnal variation in alpha 1-adrenergic regulation of the hypothalamic-pituitary-adrenal axis.     

Hormone responses to social stress in abstinent alcohol-dependent subjects and social drinkers with no history of alcohol dependence

BACKGROUND: Previous studies have described blunted stress hormone responses after pharmacological activation of the hypothalamic-pituitary-adrenal (HPA) axis in sober alcoholics. The aim of the present study was to compare ACTH, cortisol, and prolactin responses to a psychological stressor in abstinent alcohol-dependent subjects matched to healthy control subjects. METHODS: Individuals who met DSM-IV diagnostic criteria for a history of alcohol dependence but not for other axis I disorders were included in the study (n = 18; mean duration of abstinence +/- SEM, 3.5 +/- 5.7 years). Social drinkers (n = 23) served as control subjects. The sober alcohol-dependent and control subjects were matched for demographic measures including levels of stress symptoms. All subjects underwent the Trier Social Stress Test (TSST), a laboratory-based psychological stressor. Prestress and poststress plasma ACTH, cortisol, and prolactin levels, as well as a self-report measure of anxiety (State-Trait Anxiety Inventory), were obtained. RESULTS: Nondepressed, abstinent alcoholics and control subjects did not differ with regard to age, racial composition, or baseline or poststress ratings of anxiety. Whereas ACTH and cortisol levels increased in response to the TSST, prolactin levels did not. Stress hormone response curves for the three hormones did not differ between the alcoholics and control subjects. CONCLUSIONS: When matched for levels of stress, a laboratory-based psychological stress test did not induce differential hormone response curves for abstinent alcoholics and control subjects.     

Opposing influences of prenatal and postnatal weight gain on adrenarche in normal boys and girls

Associations between low birth weight and higher adrenal androgen secretion before puberty have yet only been reported in case-control studies in girls. We examined the influence of birth weight and early postnatal weight gain on overnight-fasting adrenal androgen and cortisol levels in 770 children from a large normal United Kingdom birth cohort at age 8 yr. In univariate analyses, adrenal androgen levels were inversely related to birth weight sd score in each sex [dehydroepiandrosterone sulfate in boys: regression coefficient (B) = -2.5 microg/dl/SD; 95% confidence interval (CI), -4.7 to -0.2; in girls: B = -3.8 microg/dl/SD; 95% CI, -6.2 to -1.4; androstenedione in boys: B = -0.15 nmol/liter/sd, 95% CI, -0.25 to -0.6; in girls: B = -0.13 nmol/liter/SD; 95% CI, -0.24 to -0.02). In multivariate analyses, both lower birth weight and larger current body weight predicted higher adrenal androgen levels (P < 0.005 for all comparisons). Allowing for current weight, children who showed rapid postnatal weight gain between 0 and 3 yr had higher dehydroepiandrosterone sulfate (P = 0.002) and androstenedione (P = 0.004) levels at 8 yr. In contrast, cortisol levels were unrelated to birth weight or current body size. In summary, the relationship between lower birth weight and higher childhood adrenal androgen levels was continuous throughout the range of normal birth weights, and was similar in boys and girls. Adrenal androgen levels were highest in small infants who gained weight rapidly during early childhood. We suggest that higher adrenal androgen secretion could contribute to links between early growth and adult disease risks, possibly by enhancing insulin resistance and central fat deposition.     

Differential hypothalamic-pituitary-adrenal axis reactivity to psychological and physical stress.

Healthy men exhibit a differential hypothalamic-pituitary-adrenal axis (HPA) response to exercise stress and fall into two groups: high responders (HR) and low responders (LR). The present study examined whether HR to physical stress also exhibit higher HPA reactivity to psychological stress than LR. We examined 14 HR and 13 LR classified based on their ACTH responses to high intensity exercise after pretreatment with dexamethasone. Both groups were of similar age, height, weight, and fitness level. Trait anxiety scores on the Spielberger Trait Anxiety Scale were not different. Subjects underwent a psychological stress test consisting of an interview and mental arithmetic. This test raised heart rate, blood pressure, and plasma ACTH and cortisol levels in both HR and LR. HR tended to have higher heart rates and blood pressures in anticipation of the psychological stress test than LR. ACTH responses of HR were higher, although not significantly, throughout the psychological stress test than LR. HR had a significantly (P < 0.05) greater net integrated cortisol response to the psychological stress than LR. This suggests that the adrenal cortexes of the HR are hypertropic and/or hypersensitive to ACTH. We conclude that men who are highly responsive to exercise stress are also highly responsive to psychological stress.     

High anticipatory stress plasma cortisol levels and sensitivity to glucocorticoids predict severity of coronary artery disease in subjects undergoing coronary angiography

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and/or increased sensitivity of peripheral tissues to glucocorticoids may be associated with the dysmetabolic syndrome and its cardiovascular sequelae. In this prospective pilot clinical study, we examined possible associations between HPA axis activity and severity of cardiovascular disease. We measured morning serum cortisol and intima media thickness (IMT) of carotid and femoral arteries in 105 subjects before undergoing coronary angiography for suspected coronary artery disease (CAD). In a randomly selected 46 of these subjects, we obtained late afternoon and morning cortisol levels (after ultralow-dose dexamethasone [0.25 mg] treatment) and determined their genotype for the Bcl1 polymorphism of the glucocorticoid receptor gene, which has been associated with increased sensitivity to glucocorticoids. There was significant association between morning preangiography cortisol levels and the number of vessels with severe stenosis in the angiography, independently of age or sex (P = .002), and a trend for a positive correlation between morning cortisol and the IMT of the femoral artery (P = .057). Bcl1 G allele homozygotes had a significantly higher carotid IMT (P = .005) and a nonsignificant tendency for higher waist-hip ratio (P = .059). Hyperactivity of the HPA axis in anticipation of a stressful procedure, such as angiography, may be an index of CAD severity. Chronic HPA axis hyperreactivity combined with tissue hypersensitivity to glucocorticoids may contribute to more severe atherosclerosis and CAD.     

Attenuated morning salivary cortisol concentrations in a population-based study of persons with chronic fatigue syndrome and well controls

CONTEXT: A substantial body of research on the pathophysiology of chronic fatigue syndrome (CFS) has focused on hypothalamic-pituitary-adrenal axis dysregulation. The cortisol awakening response has received particular attention as a marker of hypothalamic-pituitary-adrenal axis dysregulation. OBJECTIVE: The objective of the current study was to evaluate morning salivary cortisol profiles in persons with CFS and well controls identified from the general population. DESIGN AND SETTING: We conducted a case-control study at an outpatient research clinic. CASES AND OTHER PARTICIPANTS: We screened a sample of 19,381 residents of Georgia and identified those with CFS and a matched sample of well controls. Seventy-five medication-free CFS cases and 110 medication-free well controls provided complete sets of saliva samples. MAIN OUTCOME MEASURES: We assessed free cortisol concentrations in saliva collected on a regular workday immediately upon awakening and 30 and 60 min after awakening. RESULTS: There was a significant interaction effect, indicating different profiles of cortisol concentrations over time between groups, with the CFS group showing an attenuated morning cortisol profile. Notably, we observed a sex difference in this effect. Women with CFS exhibited significantly attenuated morning cortisol profiles compared with well women. In contrast, cortisol profiles were similar in men with CFS and male controls. CONCLUSIONS: CFS was associated with an attenuated morning cortisol response, but the effect was limited to women. Our results suggest that a sex difference in hypocortisolism may contribute to increased risk of CFS in women.     

Effects of suckling on hypothalamic-pituitary-adrenal axis responses to psychosocial stress in postpartum lactating women

In several studies lactation has been shown to be associated with a hypothalamic-pituitary-adrenal axis hyporesponsiveness to physical and psychological stressors. As it is not known whether the marked blunting of endocrine stress reactivity in women can be ascribed to suckling as a short-term effect or to lactation in general, the acute effects of suckling on the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary system responses to mental stress were investigated in lactating women. Forty-three lactating women were randomly assigned either to breast-feed or to hold their infants for a 15-min period with the onset 30 min before they were exposed to a brief psychosocial stressor (Trier Social Stress Test). Both breast-feeding and holding the infant yielded significant decreases in ACTH, total plasma cortisol, and salivary free cortisol (all P < 0.01). There were no significant differences in baseline hormone levels between the groups 1 min before the stress test. In response to stress exposure, ACTH, total plasma cortisol, salivary free cortisol, norepinephrine, and epinephrine were significantly increased in all lactating women (all P < 0.001). However, total cortisol and free cortisol responses to stress were attenuated in breast-feeding women (P = 0.001 and P = 0.067, respectively), who also showed significantly decreasing PRL levels during the stress test (P = 0.005). In addition, there was no change in plasma oxytocin or vasopressin in response to the stressor. Breast-feeding as well as holding led to decreased anxiety (P < 0.05), whereas, in contrast, stress exposure worsened mood, calmness, and anxiety in the total group (all P < 0.001). From these data we conclude that lactation in women, in contrast to that in rats, does not result in a general restraint of the hypothalamic-pituitary-adrenal axis response to a psychosocial stressor. Rather, suckling is suggested to exert a short-term suppression of the cortisol response to mental stress.     

Fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis: low birth weight and central HPA regulation

Fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as an intermediary in the association between reduced fetal growth and adult cardiovascular and metabolic diseases. Previous studies have shown that small size at birth is associated with increased fasting plasma cortisol and adrenal responsiveness to ACTH stimulation. We have extended these studies by evaluating the salivary cortisol response to awakening and plasma ACTH and cortisol responses to CRH stimulation and a dexamethasone-suppressed CRH (DEX/CRH) test in a group of low birth weight [LBW; <3.18 kg (7 lb), n = 58] and high birth weight [>3.86 kg (8.5 lb), n = 65] men aged 60-69 yr. Despite no difference in basal pituitary-adrenal activity or in their ACTH and cortisol responses to CRH, LBW men had significantly lower pituitary-adrenal responses in the DEX/CRH test. Although these findings do not explain the HPA abnormalities associated with LBW in previous studies, they provide further evidence of dysregulation of the HPA axis in people who were small at birth.