Gender differences in cardiovascular and hypothalamic-pituitary-adrenal axis responses to psychological stress in healthy older adult men and women.

Gender differences in the neuroendocrine and cardiovascular response to psychological stress may contribute to the gender differences in the prevalence of diseases associated with hypothalamic-pituitary-adrenal (HPA) axis reactivity such as cardiovascular disease (CVD), diabetes and hypertension. We measured plasma ACTH, cortisol, heart rate (HR), and blood pressure (BP) responses in 8 men and 8 women (55-75 years) exposed to the Matt Stress Reactivity Protocol (MSRP), a psychological challenge. The MSRP elicited significant increases in HR, systolic-, and diastolic BP, ACTH and cortisol (all p<0.01). Men had significantly greater cortisol and diastolic BP responses compared to women (p<0.05). Additionally, a positive correlation between the ACTH and cortisol responses was only found in the males (r=0.71, p<0.05). There were no group differences in HR, systolic BP, or ACTH responses. We conclude, that among older adults, men respond to psychological stress with greater increases in cortisol, compared to women. This greater activation of the HPA axis could translate into an elevated risk for CVD, diabetes and hypertension and may be related to the higher prevalence of these diseases in males. Gender differences in brain structures and/or cognitive processes may be responsible for these sexually dimorphic stress responses.

Estradiol modulation of central monoamine activity in female mountain spiny lizards.

Although estradiol (E2) mediates many behaviors in females, relatively little is known about its role in female aggression. Previous studies in female mountain spiny lizards indicated that female aggression is modulated by ovariectomy and sex steroid hormone replacement and that expression of aggressive behavior is accompanied by changes in serotonin activity. This study examines if E2 modulates the activity of serotonin and other central monoamines. Free-living females were caught and housed in the laboratory and received one of 3 treatments: sham surgery (SHAM), ovariectomy plus empty implant (OVEX), or sham surgery plus a long lasting E2 implant (E2-IMP). After 3 weeks of treatment, selected brain areas were examined for levels of monoamines and their metabolites. Changes in monoamine activity were most pronounced in the septum where levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine (NE) were higher in E2-IMP females relative to SHAM, and levels of 5-HIAA were higher in OVEX females relative to SHAM. Changes in dopamine (DA) activity were also found, with increased DA concentration and decreased ratio of forebrain:brainstem HVA concentrations in E2-IMP relative to SHAM females. These results suggest that the actions of E2 on aggression might be mediated, in part, by dose-dependent effects on 5-HT activity in the septum.

Neuroendocrine responses in free-living female and male lizards after aggressive interactions.

Although female aggression is found in many species and in a variety of contexts, little is known about its physiological bases. To compare neuroendocrine responses to aggression in females and males, we staged aggressive interactions between free-living territorial mountain spiny lizards and same-sex intruders and measured brain monoamines, plasma steroid hormone levels, and plasma glucose levels. Both females and males that had participated in a staged aggressive interaction had similar changes in serotonin (5-HT) activity in telencephalic tissue punches as indicated by a lowered ratio of forebrain:brainstem 5-HT concentrations. In addition, both females and males had elevated plasma corticosterone (B) after an aggressive interaction when compared to controls. The only difference detected between males and females was that females had a higher ratio of forebrain:brainstem norepinephrine (NE) concentrations throughout the brain compared to males. Together, these data indicate that acute neural and hormonal responses that accompany aggressive interactions in females are similar to those in males.

Effects of 60 Hz magnetic field exposure on the pineal and hypothalamic-pituitary-gonadal axis in the Siberian hamster (Phodopus sungorus).

Experiments using the dwarf Siberian hamster Phodopus sungorus were carried out to determine possible neuroendocrine consequences of one-time and repeated exposures to 60 Hz magnetic fields (MF). Animals were maintained in either a short-light (SL, 8 h light:16 h dark) or long-light (LL, 16 h light:8 h dark) photoperiod. Acute (one-time, 15 min) exposure of male SL animals to a linearly polarized, horizontally oriented, 60 Hz MF (0.1 mT) gave rise to a statistically significant (P < .005) reduction in pineal melatonin content as determined 3 and 5 h after onset of darkness. In LL animals, acute exposure to 0.10 mT resulted in a significant decrease in pineal melatonin as measured 4 h after onset of darkness, whereas acute exposure to 50 microT showed no effect compared with sham exposure. In SL animals, an increase in norepinephrine was observed in the medial basal hypothalamus (including the suprachiasmatic nucleus) after acute exposure (P < .01). Daily MF exposure of SL animals to a combination of steady-state and on/off 60 Hz magnetic fields (intermittent exposure) at 0.1 mT for 1 h per day for 16 days was associated with a reduction in melatonin concentrations at 4 h after onset of darkness and an increase in blood prolactin concentrations (P < .05). Exposure of SL animals to a steady state 60 Hz MF for 3 h/day for 42 days resulted in a statistically significant reduction in body weight (ANOVA: P > .05), compared with sham-exposed SL animals. At 42 days, however, no significant changes in overnight melatonin or prolactin levels were detected. In both repeated exposure experiments, gonadal weights were lowest in the MF-exposed groups. This difference was statistically significant (P < .05) after 42 days of exposure. These data indicate that both one-time and repeated exposure to a 0.1 mT, 60 Hz MF can give rise to neuroendocrine responses in Phodopus.

Energy and nutrient status of amenorrheic athletes participating in a diet and exercise training intervention program.

Chronic energy deficit is one of the strongest factors contributors to exercise-induced menstrual dysfunction. In such cases, macro- and micronutrient intakes may also be low. This study presents the results of a diet and exercise training intervention program. designed to reverse athletic amenorrhea, on improving energy balance and nutritional status in 4 amenorrheic athletes. The 20-week program provided a daily sport nutrition supplement and 1 day of rest/week. The program increased protein intakes for the 3 athletes with a protein deficit to within the recommended levels for active individuals. Micronutrient intakes increased, as did serum concentrations of vitamin B12, folate, zinc, iron, and ferritin. These results indicate that some amenorrheic athletes have poor nutritional status due to restricted EIs and poor food selections. A sport nutrition supplement may improve energy balance and nutritional status in active amenorrheic women.

An examination of individual differences in the relationship between interpersonal stress and disease activity among women with rheumatoid arthritis.

OBJECTIVE: The effects of interpersonal stress on disease activity were examined for married women with rheumatoid arthritis (RA) who differ in the quality of their relationships with their spouses. METHODS: Measures of interpersonal events were collected weekly for 12 weeks and related to disease activity through a comparison of clinician ratings and immune markers taken at baseline and during a highly stressful week for 20 RA patients. Individual differences in marital relationship variables and illness characteristics were used to predict group differences in how stress affected disease activity. RESULTS: Significant elevations in total T cell activation (DR + CD3 cells), soluble interleukin-2 receptor (sIL-2R), and clinician's global ratings of disease activity were found during a week of significant interpersonal stress. However, women with better spousal relationships did not show increases in disease activity following an episode of interpersonal stress. In addition, patients taking low-dose prednisone showed greater reactivity to stress than patients not currently using glucocorticoid treatment. CONCLUSION: The results are consistent with the hypothesis that disease activity in RA increases following increases in interpersonal stress and that women with stronger marital relationships were less vulnerable to those stressors.

Adiposity, plasma leptin concentration and reproductive function in active and sedentary females.

OBJECTIVE: Circulating leptin has recently been proposed as the peripheral signal indicating the adequacy of nutritional status for reproductive function. To test whether low plasma leptin concentration for a given degree of adiposity is associated with menstrual dysfunction, we measured plasma leptin concentration and body composition in young premenopausal women with normal or abnormal reproductive function. DESIGN: Fasting plasma leptin concentration (ELISA), body composition (dual energy X-ray absorptiometry) and menstrual status (menstrual history and hormonal profile) were assessed in 34 premenopausal women characterized by different levels of physical activity. RESULTS: Body fat content and plasma leptin concentration were both reduced in women with impaired reproductive function (amenorrheic < anovulatory < eumenorrheic women). However, after adjusting plasma leptin concentration for percentage body fat, there was no independent association between leptin and menstrual function. CONCLUSION: Menstrual abnormalities in young premenopausal women seem to occur as a consequence of the linear decline in adiposity and plasma leptin concentration observed in response to inadequate nutritional status. Levels of adiposity below 15% and plasma leptin concentration below 3 ng/ml are more likely to be associated with impaired reproductive function.

Examination of changes in interpersonal stress as a factor in disease exacerbations among women with rheumatoid arthritis.

OBJECTIVE: This study examined the effects of change in interpersonal stress on disease activity among 41 women with rheumatoid arthritis (RA). METHODS: Measures of everyday stressful events and perceived stress were collected weekly for twelve weeks and related to disease activity in a series of pooled time-series regression analyses. RESULTS: Increases in the number of interpersonal stressors in the same week and one week prior were associated with increases in disease activity. Pain from joint tenderness also was significantly related to a decrease in stressful events one week later. A subgroup of 20 patients showed a significant increase in interpersonal stress from baseline during the course of the study. For this group, significant elevations in DR + CD3 cells, sIL-2R, clinician's rating of disease, and self-reports of joint tenderness were found during the week of increased interpersonal stress. CONCLUSIONS: Interpersonal stress appears to be associated with increases in disease activity among RA patients.

Sympathetic mediation of stress and aggressive competition: plasma catecholamines in free-living male tree lizards.

The sympathetic nervous system and adrenal catecholaminergic tissue act to prepare an animal for "fight or flight" by release of catecholamines into synapses and plasma. However, few studies have measured plasma catecholamines in nonmammalian vertebrates and none have measured them in free-living animals. We report plasma levels of norepinephrine (NE), epinephrine (EPI) and dopamine (DA) in free-living tree lizards (Urosaurus ornatus) bled in the field: 1) immediately after capture, 2) after 10 minutes of restraint, 3) immediately after a staged territorial encounter and 4) four minutes after the end of a staged territorial encounter. Time to capture and time to bleed after capture were also recorded for each sample. Time to capture had little effect on plasma catecholamines suggesting that plasma catecholamines do not rise during the brief pursuit by the investigator necessary to capture the lizards in the field. In contrast, plasma NE and EPI increased during blood collection. However, this response was very consistent allowing comparisons to be made using analysis of covariance to control for time to bleed. Results indicate that restraint stress caused a large increase in plasma levels of NE, E and DA. Plasma levels of NE and E, but not plasma DA, were also significantly elevated both immediately and 4 minutes after aggressive encounters, although less so than following restraint stress. These studies show that stress and aggression activate the sympatho-adrenal system. This activation could be involved in behavioral changes during aggression, meeting metabolic demands of the encounter, or both.

Neuroendocrine correlates of separation stress in the Siberian dwarf hamster (Phodopus sungorus).

Siberian dwarf hamsters form monogamous male-female pair bonds. Disruption of the pair bond results in increases in body mass and behavioral alterations similar to profiles seen in human atypical depression. We examined behavioral and neuroendocrine correlates associated with separation of the male from his mate. Animals were paired (n = 28 pairs) for 3 weeks, then 15 pairs were separated and 13 pairs remained as controls. Behaviors of the males were observed in a novel environment following 3 weeks of pairing and 4 weeks of separation. The 5-min behavioral test monitored exploratory, territorial behavior, and locomotor activity. Separated males showed a significant increase in body mass (p < 0.01). paralleled by an increase in food consumption (p < 0.01). Separated males had decreased seminal vesicle mass (p < 0.05) and testicular mass (p < 0.05). Behavioral analysis revealed that separated males showed no significant differences in grooming, scent-marking, alert on 2 feet, or escape behavior when compared to paired males. Separated males did show significant increases in inactivity (p < 0.05). Plasma cortisol levels were significantly increased in separated animals (p < 0.05), but there were no significant effects on testosterone. Resting levels of plasma norepinephrine and epinephrine were less in separated males, but this was significant only for norepinephrine (p < 0.05). In conclusion, separation stress was accompanied by increased hypothalamic-pituitary-adrenal axis function and decreased peripheral sympathetic nervous system activity and decreased reproductive profiles.

The importance of social condition in the hormonal and behavioral responses to an acute social stressor in the male Siberian dwarf hamster (Phodopus sungorus).

Social condition is an important factor in determining the behavioral and hormonal responses to a social stressor in the Siberian dwarf hamster (Phodopus sungorus). We predict that males housed with a female or a family (female and pups) will show an increase in the magnitude of the behavioral and hormonal responses to a male intruder compared to those of individually housed males. Three treatment groups were studied: individually housed males that had been previously group-housed in same-sex colonies (males, n = 10), males housed with a female (male + female, n = 9), and males housed with their female and pups (male + family, n = 12). Males were monitored for aggressive behavior toward an intruder male for 10 min. Blood samples were taken at baseline and after the encounter. Male + female and male + family groups spent more time in aggressive behavior (P < 0.05), such as attacking (P < 0.05) and fighting (P < 0.05), than did individually housed males. These same groups showed significant increases in plasma cortisol after the encounter (P < 0.01) whereas there were no significant increases in plasma cortisol in solitary males. All groups showed significantly lower levels of plasma testosterone (male, P < 0.001, male + female, P < 0.05; male + family, P < 0.01) whereas a significant increase in prolactin occurred only in the male + family group (P < 0.05). There was a significant positive correlation between postencounter cortisol levels and total number of minutes spent in aggressive behavior (P < 0.05). These results demonstrate that the introduction of a novel intruder male results in an activation of the hypothalamic-pituitary-adrenocortical axis and a suppression of the reproductive axis. Furthermore, pairing of a male with a female alters the behavioral and hormonal responses to an intruder male.

The application of positron emission tomography to the study of the normal menstrual cycle.

Positron emission tomography (PET) was used to investigate regions of the brain that are selectively affected during different phases of the normal menstrual cycle. A total of 10 healthy 18-29 year old female volunteers had PET measurements of brain glucose metabolism between days 5 and 9 of the follicular phase when plasma concentrations of oestradiol and progesterone were relatively low and between days 5 and 8 of the luteal phase when plasma concentrations of oestradiol and progesterone were relatively high. Automated algorithms were used to align the PET images in each individual, transform them into the coordinates of a brain atlas, control for variations in whole brain measurements and compute t-score maps of phase-related differences in regional glucose metabolism. The mid-follicular phase was associated with significantly higher glucose metabolism in thalamic, prefrontal, temporoparietal and inferior temporal regions. The mid-luteal phase was associated with significantly higher glucose metabolism in superior temporal, anterior temporal, occipital, cerebellar, cingulate and anterior insular regions. While this study should be considered to be exploratory, it provides normative data for future studies and illustrates how PET can be used to help characterize relationships between phases of the female life cycle, temporally related disorders and local functions of the living human brain.

A reduced lactate mass explains much of the glycogen sparing associated with training.

Endurance training is associated with glycogen (Gly) sparing, generally attributed to less carbohydrate (CHO) oxidation. However, untrained individuals commit a greater fraction of CHO to lactate (La), accounting for a portion of the Gly "spared." We examined the effects of training (running 1 h/day at 30 m/min up an 8 degrees grade) on whole body CHO distribution and oxidation. Female Long Evans rats (n = 27) were assigned to control (Untr) and trained (Tr) groups. Two days before the experiment, animals were chronically catheterized. On the day of the experiment, animals ran for 20 min at a speed of 28 m/min and were killed with an overdose of pentobarbital sodium injection while running. Whole carcasses were then promptly freeze-clamped with a liquid N2-cooled press. Whole body carcass powder was assayed for La, Gly, and glucose. Resting whole body values were not different between groups (La = 0.78 +/- 0.06 vs. 0.83 +/- 0.07, Gly = 4.46 +/- 0.62 vs. 3.77 +/- 0.35, glucose = 0.19 +/- 0.07 vs. 0.23 +/- 0.09 mmol/body for Tr and Untr rats, respectively). However, postexercise La was higher in Untr vs. Tr group (2.01 +/- 0.28 vs. 1.13 +/- 0.09 mmol/body), and Gly was lower in the Untr vs. Tr rats (1.58 +/- 0.25 vs. 3.42 +/- 0.43 mmol/body). Similarly, Untr animals displayed higher epinephrine levels than Tr at the end of the exercise bout (4.9 +/- 1.0 vs. 1.7 +/- 0.4 ng/ml). Differences between groups in La and glucose masses (postexercise minus rest data) accounted for 60% of the Gly differences. Gly spared from oxidation and replaced by increased fat oxidation only accounted for 40% of the differences in Gly levels between Tr and Untr animals. We conclude that untrained mammals commit a significant portion of their CHO pool to La, which accounts for almost one-half of the apparent Gly spared during moderate-intensity exercise in the trained state.

Role of energy balance in athletic menstrual dysfunction.

The cessation of menstrual function in the female athlete may reflect her inability to adapt to the environmental and lifestyle stressors associated with training and competition. As society's emphasis on thinness, dieting, and exercise continues to increase, so will the incidence of menstrual dysfunction in active females. Unfortunately, some individuals view athletic menstrual dysfunction as a benign consequence of strenuous exercise. Conversely, it is most likely a strong indicator of overtraining and a marker for future decrements in performance, and it can have long-term health consequences. Thus, it is imperative that the active female be appropriately educated regarding the adverse consequences of menstrual dysfunction and the interventions available. This paper focuses on the most current information regarding athletic menstrual dysfunction and its multifactorial etiology, especially the role of energy drain. In addition, common misconceptions, adverse health and performance effects, and available treatment options are discussed.

Treatment of athletic amenorrhea with a diet and training intervention program.

The purpose of this study was to determine the effect of a 15-week diet and exercise intervention program on energy balance, hormonal profiles, body composition, and menstrual function of an amenorrheic endurance athlete. The intervention program reduced training 1 day/week and included the use of a sport nutrition beverage providing 360 kcal/day. Three eumenorrheic athletes served as a comparison group and were monitored over the same 15-week period. The amenorrheic athlete experienced a transition from negative to positive energy balance, increased body fat from 8.2 to 14.4%, increased fasting luteinizing hormone (LH) from 3.9 to 7.3 mIU/ml, and decreased fasting cortisol from 41.2 to 33.2 micrograms/dl. The eumenorrheic subjects showed a 0.4% reduction in body fat, a decrease in follicular phase levels of LH from 7.9 to 6.5 mIU/ml, and no change in cortisol. These results suggest that nonpharmacological treatment can contribute to reestablishing normal hormonal profiles and menstrual cyclicity in amenorrheic athletes.

Hormonal regulation of skeletal muscle hypertrophy in rats: the testosterone to cortisol ratio.

This study determined the influence that the catabolic hormone, corticosterone (C), and the anabolic hormone, testosterone (T), had in regulating skeletal muscle hypertrophy using the rat hind limb ablation model. Specifically, the ratio of T:C (TCR) was manipulated via hormone implants and injections and concentrations measured to evaluate the relative contribution of each hormone to skeletal muscle protein balance. Skeletal muscle growth was measured 16 days after gastrocnemius muscle ablation. Elevations in plasma concentrations of C (via daily C injections, 50 mg kg*kg(-1) body mass) resulted in TCR of 0.007 that was less than the control group TCR of 0.249. In this C-injected group, whole body and skeletal muscle atrophy was elicited-this being greater in the fast-twitch plantaris muscle than in the slow-twitch soleus muscle. The overloaded leg resisted the C-induced atrophy. Castration of animals (TCR 0.024) resulted in less whole body and skeletal muscle growth. However, elevations in plasma concentrations of T (two groups, with TCR of 1.35 and 1.64) did not result in significantly greater muscle growth. Furthermore, T was also ineffective in antagonizing the C-induced atrophy in a group that received both T implants and C injections. This group had a TCR of 0.175 that was similar to the control group ratio of 0.249 that received no manipulations. We concluded that glucocorticoids were able to induce pronounced atrophy, but at the same time overloaded muscles were able to over-ride the glucocorticoid signal. Plasma concentrations of C were a better predictor of muscle growth/atrophy than T and/or the TCR. In addition, it is suggested that the volume of contractile activity of the muscle is perhaps an important determinant of C-induced atrophy, because less atrophy occurs in the more active slow twitch muscles.

Gender does not influence sympathetic neural reactivity to stress in healthy humans.

Previous data support the idea of heightened sympathetically mediated cardiovascular reactivity in males. However, definitive conclusions cannot be made because of inconsistent reports, possibly stemming from imprecise measurement of sympathetic activity and/or failure to equate the stress stimuli between genders. The present study tested the hypothesis that males exhibit heightened sympathetic reactivity that is associated with heightened cardiovascular and plasma catecholamine responses. In 37 healthy adults (20 males, 17 females: age = 20-42 yr), direct recordings of skeletal muscle sympathetic nerve activity (MSNA), plasma catecholamines, heart rate, blood pressure, and perceived stress were measured before and during three laboratory stressors (isometric handgrip, cold pressor, and mental arithmetic). MSNA, catecholamine, and cardiovascular reactivity (defined as change from rest) were not consistently different between genders. For the isometric handgrip, when expressed as absolute unit changes, males had larger MSNA responses (P < 0.01), which were partially explained by greater contraction force; they did not differ in terms of percent change from baseline or in perceived stress. The responses to the cold pressor and mental arithmetic tasks were similar between genders. These findings indicate that stress-evoked vasoconstrictor neural excitation and the associated increases in blood pressure are not consistently influenced by gender.

Interpersonal stress, depression, and disease activity in rheumatoid arthritis and osteoarthritis patients.

The relationships among interpersonal stressors, depression, coping inefficiency, hormones (prolactin, cortisol, and estradiol), and disease activity were examined. The sample comprised 33 women with rheumatoid arthritis (RAs; age 37-78) and 37 women with osteoarthritis (OAs; age 47-91), who served as controls. In a regression analysis, interpersonal conflict events accounted for more than twice as much variance in depression in RAs than in OAs. In the RA patients, the immune-stimulating hormones prolactin and estradiol were significantly positively correlated with interpersonal conflicts, depression, coping inefficacy, and clinician ratings of disease activity, suggesting that RAs are more reactive to interpersonal stressors than are OAs, both psychologically and physiologically.

The influence of photoperiod on gonadotrophin-releasing hormone stimulated luteinising hormone release in the anoestrous mare.

The transition from anoestrus to oestrus in mares is controlled by photoperiod. The present study examined whether additional daylength would accelerate the mares' response to gonadotrophin-releasing-hormone (GnRH). Nine anoestrous mares were placed under ambient or artificial long lighting on 7th January. The four month experimental period was divided into a three-day sequence which was repeated at 21 day intervals. Ovaries were palpated rectally on Day 1; saline was injected (1 ml intravenously [iv]) on Day 2; GnRH was administered (0.59 microgram/kg bodyweight iv) on Day 3. Blood was taken at -60, 0, 15, 30, 60 and 120 mins relative to saline or GnRH treatment. Serum luteinising hormone (LH) was determined by a homologous equine radioimmunoassay (RIA). Several criteria were employed to define a positive response to GnRH and the results were analysed by Fisher's exact probability test. Treatment with artificial light allowed a response to GnRH within six weeks whereas the mares in ambient lighting took 12 weeks to respond to GnRH. The advancement in the time of response to GnRH under the long photoperiod could be related to changes in pituitary LH content, accelerated follicular activity or alterations in other brain-pituitary hormone levels.

Hyperprolactinemia preferentially inhibits erectile function in adrenalectomized male rats.

To determine if the inhibitory effects of hyperprolactinemia on sexual arousal and serum LH levels could be dissociated from those on erectile function, copulatory behavior was examined in pituitary-grafted, adrenalectomized male rats that had been castrated and given 20mm subcutaneous testosterone implants. Whereas transplantation of three pituitaries under the kidney capsules inhibited mounting rates in intact animals, pituitary grafting did not significantly reduce mounting rates in the adrenalectomized group beyond the effect of adrenalectomy alone. In contrast, the effects of pituitary grafting on erectile function were enhanced in the adrenalectomized animals. Hyperprolactinemia also caused a significant reduction in serum LH, but only in the intact animals. These results suggest that: 1. the effects of hyperprolactinemia on erectile function occur independently from those on sexual arousal, and 2. the inhibitory effects of hyperprolactinemia on sexual arousal are linked to the effects of hyperprolactinemia on LH release.