Kathleen S. Matt

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 <formula><italic>p</italic><0.01</formula>). Men had significantly greater cortisol and diastolic BP responses compared to women <formula>(<italic>p</italic><0.05).</formula> Additionally, a positive correlation between the ACTH and cortisol responses was only found in the males (<formula><italic>r</italic>=0.71,</formula> <formula><italic>p</italic><0.05</formula>). 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.

The HPA axis response to stress in women: effects of aging and fitness

This study tested the hypotheses that aging is associated with greater hypothalamic-pituitary-adrenal (HPA) axis reactivity to psychological stress, and whether aerobic fitness is associated with a lower HPA axis response to psychological stress. Three groups, consisting of young-unfit women (27.9+/-2.5 yr, n=10), older-unfit women (66.3+/-1.4 yr, n=14), and older-fit women (66.6+/-2.0 yr, n=12), underwent the Matt Stress Reactivity Protocol (MSRP). The MSRP is a stress test battery that combines mental challenges, a physical challenge, and a psychosocial stressor. Definition of fitness was based on maximal oxygen consumption (VO(2max)) where unfit was defined as having VO(2max)</=average for the respective age group and fit was defined as VO(2max)>average for the respective age group. The MSRP elicited increases in heart rate, blood pressure, ACTH, and cortisol (P<0.001). The older-unfit women had significantly greater cortisol responses to the challenge than both the young-unfit and the older-fit women (P<0.05), who did not differ from each other. ACTH levels were significantly higher in the older-unfit women at baseline and throughout the trial, compared to both young-unfit and the older-fit (P<0.01). The ACTH response was not different between any of the groups. The young-unfit women had greater heart rate responses than the older-unfit (P<0.01), while the latter had greater systolic blood pressure responses (P<0.01). There were no significant differences between the older-unfit and older-fit in terms of heart rate or blood pressure responses. Our result shows that among unfit women, aging is associated with greater HPA axis reactivity to psychological stress, and that higher aerobic fitness among older women can attenuate these age-related changes as indicated by a blunted cortisol response to psychological stress. These findings suggest that exercise training may be an effective way of modifying some of the neuroendocrine changes associated with aging.

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, clinicians 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

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.

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−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/atropy 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.

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.

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.

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.

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.

Effects of the oral contraceptive pill cycle on physiological responses to hypoxic exercise.

To test whether the oral contraceptive pill cycle affects endocrine and metabolic responses to hypoxic (fraction of inspired oxygen = 13%, P(IO2): 95 mmHg; H) versus normoxic (P(IO2):153 mmHg; N) exercise, we examined eight women (28 +/- 1.2 yr) during the third (PILL) and placebo (PLA) weeks of their monthly oral contraceptive pill cycle. Cardiopulmonary, metabolic, and neuroendocrine measurements were taken before, during, and after three 5-min consecutive workloads at 30%, 45%, and 60% of normoxic V(O2peak) in H and N trials. Heart rate response to exercise was greater in H versus N, but was not different between PILL and PLA. Lactate levels were significantly greater during exercise, and both lactate and glucose levels were significantly greater for 30 min after exercise in H versus N (p < 0.0001). When expressed relative to baseline, lactate levels were lower in PILL versus PLA, but glucose was greater in PILL versus PLA (p < 0.001). Cortisol levels were also significantly greater in PILL versus PLA (p < 0.001). Norepinephrine levels were significantly increased during exercise (p < 0.0001) and in H versus N (p < 0.0001). However, epinephrine levels were not different over time or with trial. Thus, the presence of circulating estradiol and progesterone during the PILL phase reduces glucose and lactate responses to hypoxic exercise.