Ability of corticotropin releasing hormone to stimulate cortisol secretion independent from pituitary adrenocorticotropin

Cortisol secretion by the adrenal cortex is thought to depend upon a preceding release of pituitary ACTH. This concept ignores a large number of observations suggesting important extrapituitary influences on adrenocortical function. The present study was designed to demonstrate the contribution of these extrapituitary mechanisms in the release of cortisol induced by human corticotropin releasing hormone (hCRH) in man. In patients with proven deficiency in pituitary ACTH the functional atrophy of the adrenals had been restored by pretreatment with long-acting ACTH. Fifty-eight hours after the second and last injection of ACTH a CRH test was performed (100 micrograms hCRH intravenously). Administration of hCRH induced a small but significant increase in plasma cortisol. Surprisingly, this rise was preceded by an increase in plasma ACTH similar to the ACTH response observed in the control group. It appeared that hCRH is able to stimulate cortisol release in the absence of pituitary ACTH, presumably by stimulating extrapituitary sources of ACTH.     

The awakening cortisol response and blood glucose levels

The hypothalamic-pituitary-adrenal axis is characterized by a marked circadian cycle with heightened activity in the morning. This is synchronized to awakening such that free cortisol increases two to three fold in the first thirty to forty five minutes following awakening -- the awakening cortisol response. It has been suggested that this activity, by mobilizing energy reserves prepares the body for the metabolic demands of the day. Similar arguments are applied to the cortisol response to psychological challenge. Paradoxically the cortisol response to a psychosocial stressor is abrogated in fasted individuals with low blood glucose. Also cortisol response to a psychosocial stressor is positively correlated to blood glucose levels after glucose load. We examined if the same relationship applies to the awakening cortisol response. There was no correlation between the cortisol response and awakening blood glucose levels. Moreover a group with mean blood glucose at the bottom of the euglycemic range, identified by split at the median for glucose level upon awakening, showed no deficit in cortisol response. Hence the physiology of the awakening response differs to that of a psychological stress response. These data challenge the view that an oxidisable substrate for energy metabolism is permissive for cortisol responses. In addition the present findings do not support a predominantly gluconeogenic role for morning cortisol activation.     

Circadian cortisol secretion and circadian adrenal responses to ACTH are maintained in dexamethasone suppressed capuchin monkeys (Cebus apella)

We tested the hypothesis that the capuchin monkey adrenal (Cebus apella) gland has oscillatory properties that are independent of adrenocorticotropic hormone (ACTH) by exploring under ACTH suppression by dexamethasone: (i) maintenance of a circadian rhythm of plasma cortisol and (ii) clock time dependency of plasma cortisol response to exogenous ACTH. The capuchin monkey had a clear ACTH and plasma cortisol rhythm. Dexamethasone treatment resulted in low non-rhythmic ACTH levels and decreased cortisol to 1/10 of control values; nevertheless, the circadian rhythm of plasma cortisol persisted. We found that cortisol response to exogenous ACTH was clock time-dependent. The maximal response to ACTH occurred at the acrophase of the cortisol rhythm (0800 h). These results suggest that the capuchin monkey adrenal cortex may possess intrinsic oscillatory properties that participate in the circadian rhythm of adrenal cortisol secretion and in the circadian cortisol response to ACTH.     

Plasma adrenocorticotropin and cortisol responses to brief high-intensity exercise in humans

The purpose of this study is to examine plasma cortisol and adrenocorticotropin (ACTH) levels following a brief high-intensity bout of exercise. Each subject (n = 6) performed a 1-min bout of exercise on a cycle ergometer at 120% of his maximum O2 uptake. Blood samples were collected at rest, immediately following the exercise bout, and at 5, 15, and 30 min postexercise. Mean (+/- SE) plasma ACTH levels increased significantly (P less than 0.05) from 2.2 +/- 0.4 pmol/l at rest to 6.2 +/- 1.7 pmol/l immediately following exercise. Mean (+/- SE) plasma cortisol levels increased significantly from 0.40 +/- 0.04 mumol/l at rest to 0.52 +/- 0.04 mumol/l at 15 min postexercise. These data show that brief high-intensity exercise results in significant increases in plasma cortisol and ACTH levels. Furthermore, the temporal sequence between the two hormones suggests that the increase in plasma cortisol levels following brief high-intensity exercise is the result of ACTH-induced steroidogenesis in the adrenal cortex.     

Human corticotropin-releasing hormone test in normal subjects and patients with hypothalamic, pituitary or adrenocortical disorders

Human corticotropin-releasing hormone (hCRH) test was performed in 57 normal volunteers and 102 patients with hypothalamic, pituitary and adrenocortical diseases. Intravenous bolus injection of synthetic hCRH, 100 micrograms for adults or 1.5 micrograms/kg for children, increased plasma ACTH and cortisol levels in about 90% of normal subjects. In 47 patients with Cushing's disease, plasma ACTH tended to show an exaggerated response to hCRH and peak ACTH was the most frequent abnormal component among the several reaction parameters. Poor responders among normal subjects and patients with Cushing's disease had significantly higher plasma cortisol levels before CRH administration. Patients with hypothalamic hypopituitarism showed exaggerated response, whereas patients with primary pituitary lesion, isolated ACTH deficiency or adrenal Cushing's syndrome showed no ACTH response. These differences in the response of patients suggest the value of the hCRH test in their differential diagnosis.     

The inhibitory action of corticotropin-releasing hormone on gonadotropin secretion in the ovariectomized rhesus monkey is not mediated by adrenocorticotropic hormone

Earlier observations in our laboratory indicated that i.v. infusion of human/rat corticotropin-releasing hormone (hCRH) suppresses pulsatile luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release in ovariectomized rhesus monkeys. Since cortisol secretion increased significantly as well, it was not possible to exclude the possibility that this inhibitory effect of hCRH on gonadotropins was related to the activation of the pituitary/adrenal axis. The purpose of the present study was to determine the role of pituitary/adrenal activation in the effect of hCRH on LH and FSH secretion. We compared the effects of 5-h i.v. infusions of hCRH (100 micrograms/h, n = 7) and of human adrenocorticotropic hormone (ACTH) (1-24) (5 micrograms/h, n = 3; 10 micrograms/h, n = 3, 20 micrograms/h, n = 3) to ovariectomized monkeys on LH, FSH, and cortisol secretion. As expected, during the 5-h ACTH infusions, cortisol levels increased by 176-215% of baseline control, an increase similar to that observed after CRH infusion (184%). However, in contrast to the inhibitory effect observed during the CRH infusion, LH and FSH continued to be released in a pulsatile fashion during the ACTH infusions, and no decreases in gonadotropin secretion were observed. The results indicated that increases in ACTH and cortisol did not affect LH and FSH secretion and allowed us to conclude that the rapid inhibitory effect of CRH on LH and FSH pulsatile release was not mediated by activation of the pituitary/adrenal axis.     

Sensitivity to stress-induced reproductive dysfunction is associated with a selective but not a generalized increase in activity of the adrenal axis

Stress-induced reproductive dysfunction is a relatively common cause of infertility in women. In response to everyday life stress, some individuals readily develop reproductive dysfunction (i.e., they are stress sensitive), whereas others are more stress resilient. Female cynomolgus monkeys, when exposed to mild combined psychosocial and metabolic stress (change in social environment + 20% reduced calorie diet), can be categorized as stress sensitive (SS; they rapidly become anovulatory in response to stress), medium stress resilient (MSR; they slowly become anovulatory in response to prolonged stress), or highly stress resilient (HSR; they maintain normal menstrual cycles in response to stress). In this study, we examined whether increased sensitivity to stress-induced reproductive dysfunction is associated with elevated adrenal axis activity by measuring 1) the diurnal release of ACTH and cortisol, 2) ACTH and cortisol in response to an acute psychological stress, 3) the percent suppression of cortisol in response to dexamethasone negative feedback, 4) the diurnal release of ACTH and cortisol following exposure to mild psychosocial and metabolic stress, 5) the concentration of cortisol in hair, and 6) adrenal weight. SS monkeys (n = 5) did not differ from MSR (n = 5) or HSR (n = 7) monkeys in any measurement of baseline HPA axis activity or the integrated measurements of chronic HPA axis activity. However, MSR + SS monkeys (n = 10) did secrete more cortisol than HSR monkeys during the daytime hours (1000-1800) following exposure to a novel social environment and reduced diet. We conclude that increased activity of the HPA axis is unlikely to be the primary mechanism causing increased sensitivity to stress-induced reproductive dysfunction.     

Effects of a long-acting somatostatin analogue on pituitary-adrenocortical secretion in normal human subjects

A potent and long-acting somatostatin analogue, SMS 201-995 (SMS) is currently employed for the treatment of various diseases with hypersecretion of hormones such as acromegaly and gastrinoma. The suppressive effects of SMS are also reported on the other pituitary and gastrointestinal hormones. The corticotropic-adrenocortical axis is a crucial hormonal complex in maintaining normal activity and life itself. In this study, the effects of SMS on corticotropic-adrenocortical functions were studied, since the effects of SMS on this hormonal axis are not well established. Seven normal males received a sc injection of 100 micrograms SMS or placebo at 0830 h and 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) intravenously (SMS-hCRH study). Five of the 7 subjects were given an injection of a synthetic (1-24) ACTH (250 micrograms or 63 micrograms) at 0900 h after 100 micrograms SMS or a placebo at 0830 h (SMS-ACTH study). Blood samples were drawn at -30, 0, 15, 30, 60, 90 and 120 min after the hCRH injection for the determination of ACTH and cortisol in the SMS-hCRH study, and cortisol and aldosterone in the SMS-ACTH study. Although significant rises in plasma ACTH and cortisol levels were observed regardless of the preinjection of SMS, their responses to hCRH were significantly lower with the pretreatment with SMS than without SMS. A significant increase in plasma cortisol and aldosterone was observed in response to synthetic ACTH with both ACTH alone and the combined administration of SMS and ACTH, at either dose of ACTH. However, no significant difference in cortisol and aldosterone secretion was detected with and without SMS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of cortisol on cyclic AMP production stimulated by 1-24 ACTH in adrenal cortex membranes

The effect of cortisol on cyclic AMP production by crude bovine adrenal cortex membrane preparations has been investigated. Results demonstrate that in the presence of cortisol, cyclic AMP production in response to 1-24 ACTH was enhanced up to a concentration of about 74 microM cortisol. At higher concentrations the effect was reversed. Cortisol had no effect on cyclic AMP production in the absence of 1-24 ACTH, and cyclic AMP production was completely inhibited when 5 mM EDTA was added to the incubation tubes with the cortisol.     

Effects of nighttime low frequency noise on the cortisol response to awakening and subjective sleep quality

The effects of night-time exposure to traffic noise (TN) or low frequency noise (LFN) on the cortisol awakening response and subjective sleep quality were determined. Twelve male subjects slept for five consecutive nights in a noise-sleep laboratory. After one night of acclimatisation and one reference night, subjects were exposed to either TN (35dB L(Aeq), 50dB L(Amax)) or LFN (40dB L(Aeq)) on alternating nights (with an additional reference night in between). Salivary free cortisol concentration was determined in saliva samples taken immediately at awakening and at three 15-minute intervals after awakening. The subjects completed questionnaires on mood and sleep quality. The awakening cortisol response on the reference nights showed a normal cortisol pattern. A significant interaction between night time exposure and time was found for the cortisol response upon awakening. The awakening cortisol response following exposure to LFN was attenuated at 30 minutes after awakening. Subjects took longer to fall asleep during exposure to LFN. Exposure to TN induced greater irritation. Cortisol levels at 30 minutes after awakening were related to "activity" and "pleasantness" in the morning after exposure to LFN. Cortisol levels 30 minutes after awakening were related to sleep quality after exposure to TN. This study thus showed that night time exposure to LFN may affect the cortisol response upon wake up and that lower cortisol levels after awakening were associated with subjective reports of lower sleep quality and mood.     

Salivary cortisol increases after bariatric surgery in women

Cortisol increases have been associated with psychological and physiological stress; however, cortisol dynamics after weight loss (bariatric) surgery have not been defined. Obese participants not using exogenous glucocorticoids were eligible to participate. Female participants (n=24) provided salivary cortisol samples at bedtime, upon awakening the following morning, and 30?min after awakening before, and at 6 or 12 months after bariatric surgery. The Medical Outcomes Study Short Form-12 version 2 questionnaire regarding health-related quality of life was also completed. Preoperatively, mean body mass index was 45.1±8.1?kg/m2. Mean late night (1.8±1.1?nmol/l), awakening (10.7±7.4?nmol/l), and after-awakening (11.5±7.9?nmol/l) salivary cortisol values were within normal ranges. The cortisol awakening response (mean 21.1±79.7%, median 13.7%) was at the low end of normal. Preoperatively, participants had lower mental and physical health-related quality of life scores than US adult norms (p<0.001). Salivary cortisol was not correlated with measures of health-related quality of life. Mean BMI decreased over time (p<0.001) and participants experienced improved physical and mental health-related quality of life (p≤0.011). Postoperative late night salivary cortisol was not different from preoperative values. Awakening and after-awakening cortisol levels were higher than preoperative values (15.3±7.7?nmol/l, p=0.013; 17.5±10.2?nmol/l, p=0.005; respectively), but the cortisol awakening response was not changed (mean 26.7±66.2%; median 7.8%). Morning salivary cortisol increased at long-term follow-up after bariatric surgery. Although self-evaluated mental and physical health improved after surgery, the cortisol awakening response is at the low end of normal, which may indicate continued physiological stress.     

The time-course of ACTH stimulation of cortisol synthesis by the immature ovine foetal adrenal gland.

The aim of this study was to establish the time-course of foetal adrenal gland activation by ACTH at a period of intra-uterine development during which adrenal function is minimal (100-120 days of gestation). Blood samples for cortisol analysis were collected at 6-h intervals during the 24 h ACTH (0.05, 0.5 and 5.0 micrograms/h) infusion and during the subsequent 24-h period following cessation of the infusion. Plasma cortisol concentrations were measured using a newly developed radioimmunoassay, whose sensitivity was found to be comparable to that of the validated double-isotope dilution derivative method. There was a significant increase in foetal plasma cortisol concentration, from 3.9 +/- 1 to 17.8 +/- 1.9 nmol/l, within 12 h of commencement of the 2 higher doses of ACTH. Values are mean +/- SEM; n = 5. Following termination of the infusion, cortisol levels fell significantly by the first 6 h, returning to basal levels thereafter. An increase in plasma ACTH from 4.6 +/- 0.6 to 8.4 +/- 1.0 pmol/l was sufficient to initiate a significant increase in cortisol production. The results suggest that the normal low values of cortisol at this period of gestation result from inadequate endogenous ACTH production at this stage.     

Atrial natriuretic factor inhibits the CRH-stimulated secretion of ACTH and cortisol in man.

Corticotrophic secretion of ACTH is stimulated by corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), and suppressed by glucocorticoids. In vitro and preclinical studies suggest that atrial natriuretic factor (ANF) may be a peptidergic inhibitor of pituitary-adrenocortical activity. The aim of this study was to elucidate a possible role of ANF as a modulator of ACTH release in humans. A bolus injection of 100 micrograms human CRH (hCRH) during a 30 min intravenous infusion of 5 micrograms/min human alpha atrial natriuretic factor (h alpha ANF) was administered at 19:00 to six healthy male volunteers. In comparison to saline, a blunted CRH-stimulated secretion of ACTH (mean maximum plasma level +/- SD 45 min after hCRH: saline 46.2 +/- 14.2 pg/ml, h alpha ANF 34.6 +/- 13.8 pg/ml, p-value = 0.007) and a delayed rise (10 min) in cortisol were detected. The maximum plasma cortisol levels remained nearly unchanged between saline and h alpha ANF administration (mean maximum plasma level +/- SD 60 min after hCRH: saline 182 +/- 26 ng/ml, h alpha ANF 166 +/- 54 ng/ml). No effects of h alpha ANF on basal cortisol levels were observed; in contrast, basal ACTH plasma levels were slightly reduced. Basal blood pressure and heart rate remained unaffected. In the control experiment, infusion of 3 IU AVP in the same experimental paradigm increased basal and stimulated ACTH and cortisol levels significantly in comparison to saline. These observations suggest that intravenously administered haANF inhibits the CRH-stimulated release of ACTH in man.     

Sex differences in cortisol secretion after administration of an ACTH analogue in sheep during the breeding and non-breeding season

The aim of this study was to compare the response of cortisol in sheep of different sex and gonadal status to adrenal cortex stimulation by an ACTH analogue in the breeding and non-breeding season. Twenty-four adult Corriedale sheep were used in the non-breeding season, and 19 in the breeding season. Three weeks prior to the first trial (non-breeding season), six rams and six ewes were gonadectomised. In each trial, blood was obtained every 15min for 9h and the animals received 0.5mg of ACTH (Tetracosactid, Synacthen Depot i.m., after 1.5h of sampling. Sampling began at 10:00a.m. in the non-breeding season and at 9:00a.m. in the breeding season. Three main effects (sex, gonadal status and season) were evaluated, each with two levels (male and female, intact and gonadectomised, breeding and non-breeding season, respectively). In both seasons, the females showed higher cortisol levels after ACTH than males (P<0.001), though the difference seemed less marked in the non-breeding season. The cortisol response in the ewes was not affected by season. The rams, however, showed a lower response in the breeding season (P<0.03). Gonadectomy reduced the response in the ewes (P<0.001) but had no effect in the rams. Nevertheless, gonadectomy also eliminated the differences between the ewes and the rams, such that the intact rams had lower levels of cortisol compared to the intact females, with those of the gonadectomised animals of both sexes being intermediate between the gonad-intact groups. The results of this study confirm sex differences in ACTH induced cortisol secretion in intact sheep in vivo. Furthermore, by applying exogenous ACTH we have directly stimulated the adrenal cortex, indicating the existence of sex differences also at this level. The circulating gonadal steroids, which are responsible at least in part for the sex differences in the responses to stress, may influence cortisol secretion from the adrenal gland by direct action at the cortex.     

Dissociation of adrenal androgen and cortisol levels in acute stress

Patients recovering from acute surgical stress often excrete increased 17-OH corticosteroids with no change in 17-ketosteroids. The explanation for these findings is unclear. In order to investigate possible divergence between cortisol and adrenal androgen metabolism in acute stress, repeated morning cortisol and dehydroepiandrosterone (DHA) measurements were made in patients undergoing ACTH stimulation 48 to 96 hours preoperatively, followed by determinations before and during major surgery, also performed in the morning. Cortisol and DHA are largely metabolized by the liver, so liver blood flow under a constant general anesthetic regimen known not to affect cortisol metabolism was monitored by pre- and intraoperative indocyanine green dye clearance. Results indicated no difference between the cortisol and DHA stimulation resulting from two hours of ACTH stimulation or major surgery, and a small (14.4%) decline in hepatic blood flow during general anesthesia. However, while DHA concentrations remained constant immediately preceding surgery, cortisol concentrations increased by 61% (P less than 0.05). Previous studies have also demonstrated increased concentrations of cortisol before surgical procedures, presumably due to psychological stress. However, this is the first demonstration of a dissociation between concentrations of cortisol and an adrenal androgen due to psychological stress.     

Variable sensitivity to the glucocorticoid activity of cortisol in patients with primary adrenal insufficiency: assessment with ACTH profiles

Our aim was to investigate the usefulness of circulating levels of adrenocorticotropic hormone (ACTH) and also salivary cortisol to monitor cortisone substitution in patients with Addison's disease. 13 patients with primary adrenal insufficiency (8 women and 5 men, age 44 ± 11 years) received 12.5 mg cortisone acetate orally at 16:00 h and 25 mg at 07:00 h. Blood samples for cortisol and ACTH analysis were drawn every hour for 24 h, and also every half hour between 07:00 and 12:00 h. Samples for salivary cortisol were collected in parallel. Total ACTH levels showed large inter-individual variations and a diurnal rhythm with a nadir in the early evening at 19:00 (median 19 ng/l, range 2-434 ng/l) and high levels in the early morning, with a peak around 07:30 (median 844 ng/l, range 45-2,249 ng/l). Plasma cortisol concentrations showed 2 peaks distinct in time, but variable in height, 1-2 h after intake of cortisone. Plasma cortisol correlated significantly with ln(ACTH) at 17:00 h (r=-0.56), at 10:00 h (r=-0.51), and at 10.30 h (r=-0.57). When tested at different time points, ln(ACTH) at 10:00 to 12:00 h was negatively correlated with plasma cortisol between 08:30 and 12:00 h. Plasma cortisol was highly correlated to ln(salivary cortisol) most of the time points measured, but 30-60 min after intake of cortisone acetate the correlation disappeared. In conclusion, the large interindividual variation in ACTH levels most likely indicates varying sensitivity to cortisol with a need for individualized dosing schemes. Furthermore ACTH-determinations may be useful for dose titration of cortisol.     

Effect of ACTH-challenge on progesterone and cortisol levels in ovariectomised repeat breeder heifers

In order to investigate the potential influence of stress as a component of the repeat breeding syndrome, the adrenocortical capacity for steroid production was evaluated in ovariectomised dairy heifers. In repeat breeder heifers (RBH), marginally elevated plasma progesterone levels during oestrus, so-called suprabasal progesterone levels, have earlier been measured and are believed to impair fertility. The aim was to distinguish if this progesterone could be of extra-gonadal or in this case, adrenal origin. Baseline levels of plasma cortisol and progesterone were determined as well as the corresponding response after induced acute stress in the form of an adrenocorticotropin (ACTH)-challenge. Comparisons were made between strictly selected RBH, n=5 and virgin heifers (VH), n=5 of the Swedish Red and White breed. The heifers were used as their own pre-challenge controls in a 2-day trial. On the control day, saline was injected i.v. and on the treatment day, a synthetic analogue of ACTH (60 microg Synachten(R)). Via a jugular vein catheter, blood samples were collected every 30 min for 6 h each day of the experiment. Analyses for plasma progesterone and cortisol were made. RBH had a significantly higher (P<0.01) pretreatment baseline cortisol level (10.1+/-2.3 nmol l(-1)) than VH (2.6+/-0.2 nmol l(-1)). Moreover, the cortisol response after stimuli was stronger in RBH than VH, especially concerning total hormone production (P<0. 001), but there was also a tendency towards higher peak values (P=0. 06) and longer duration of significantly increased hormone concentrations (P=0.08). Progesterone concentrations, however, did not differ between the groups. Both baseline levels (P=0.25) and posttreatment production (P=0.45) were of the same magnitude in RBH and VH. In conclusion, the study could not confirm that suprabasal progesterone concentrations during oestrus in RBH derive from the adrenal glands. Still, apparent differences were found in adrenocortical activity when ovariectomised heifers, VH and RBH, were subjected to an ACTH-challenge. It is suggested that a sustained adrenal stimulation associated with environmental or social stress could be one factor in the repeat breeding syndrome.     

Exploration of the awakening cortisol response in relation to diurnal cortisol secretory activity

Adrenocortical activity can be assessed by measurement of free cortisol in saliva. Cortisol status has important health implications in both physical and psychological terms. Assessment of cortisol status is complicated by the marked diurnal cortisol cycle. This cycle is characterised by an increase in secretory activity following awakening to achieve the morning acrophase. Thereafter it falls with a declining trend over the remainder of the day. For between subject studies the timing of sampling in relation to this cycle is an important consideration. We report a comprehensive study of the diurnal free cortisol cycle designed to analyse its components and to investigate their reliability and inter-relatedness. We instructed 42 healthy volunteers to collect saliva samples at home on two consecutive days. On each day the first sample was collected immediately upon awakening, followed by a further three samples at 15-minute intervals which collectively comprised the "awakening samples". A further four sample's were collected through the day at 3-hour intervals, all synchronized to awakening time. The cortisol response to awakening was calculated in two ways. Overall cortisol production in the first 45 minutes after awakening was calculated as area under the cortisol curve with reference to zero (AUC). The dynamic of the cortisol response to awakening was calculated as area under the cortisol response curve (AURC) with reference to the first awakening sample. In addition the underlying cortisol secretory activity was assessed based upon the diurnal three-hourly samples. All three parameters of adrenocortical activity showed reasonable stability across the two sampling days indicating all were reliable indexes of trait characteristic. AUC was representative of underlying diurnal activity but AURC was not. Measurement at any time point, 3, 6, 9 or 12 hours post-awakening was representative of the underlying 12-hour diurnal activity.     

Adrenal activation and the prolactin response to exercise in eumenorrheic and amenorrheic runners.

Adrenocorticotropic hormone (ACTH), cortisol, and prolactin responses following maximal and submaximal (40 min at 80% maximal O2 consumption) running were studied in eumenorrheic (ER; n = 8, 29.0 +/- 1.5 yr) and amenorrheic (AR; n = 8, 24.5 +/- 2.0 yr) runners. ER were studied in the early follicular and midluteal phases of the menstrual cycle. Physical, training, and gynecological characteristics were similar, and cardiorespiratory and metabolic responses to the exercises were indistinguishable in the groups. ACTH, cortisol, and prolactin data from the follicular luteal phases in ER were combined for comparison to AR, because no differences were noted between the menstrual phases at rest. Similar preexercise ACTH levels and responses following exercise occurred in both groups, but preexercise cortisol levels were elevated (ER = 293.1 +/- 46.3, AR = 479.6 +/- 42.4 nmol/l) and cortisol responses blunted in AR. Adrenal sensitivity was blunted in AR compared with ER after submaximal (ER = 121.9 +/- 17.4, AR = 51.7 +/- 13.6) and maximal exercise (ER = 27.9 +/- 9.2, AR = 12.1 +/- 3.8). Preexercise prolactin levels were reduced (ER = 16.4 +/- 2.7, AR = 10 +/- 2.3 micrograms/l), and prolactin responses to maximal exercises were blunted in AR, despite high lactate levels (11.4 +/- 0.4 mmol/l). We conclude that 1) control for menstrual phase in ER is important in studies of prolactin responses following exercise but not in studies of ACTH and cortisol responses following exercise, 2) cortisol responses following submaximal and maximal exercise in AR are blunted at the adrenal level, 3) prolactin responses following submaximal and maximal exercise are also blunted in AR, and 4) prolactin responses following exercise may be mediated by adrenal activation.     

Individual differences in the diurnal cortisol response to stress

The objectives of this study were to explore individual differences associated with diverse reactions in cortisol secretion under different stress levels. This study was part of a larger project concerning working hours and health. Thirty-four white-collar workers participated under two different conditions; one work week with a high stress level (H) and one with a lower stress level (L) as measured through self-rated stress during workdays. Based on the morning cortisol concentration during a workday subjects were divided into two groups. One group consisted of subjects whose morning level of cortisol increased in response to the high-stress week, compared to their morning levels in the low-stress condition (Group 1). The other group consisted of subjects whose morning cortisol response was the opposite, with a lower level under the high stress condition (Group 2). Subjects wore actiwatches, completed a sleep diary, and rated their sleepiness and stress for one work week in each condition, i.e., high and low stress. Saliva samples for measures of cortisol were collected on a Wednesday. Group 2 reported higher workload, fatigue, and exhaustion during both weeks. Since there were no differences in perceived stress, neither within nor between groups, the data indicate that there are other factors influencing morning cortisol. The results suggest that one component modulating the cortisol response might be the level of exhaustion, probably related to work overload. Higher levels of stress in exhausted individuals might suppress morning cortisol levels.