This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Heinrichs, M. Articles by Hellhammer, D. H. Search for Related Content PubMed PubMed Citation Articles by Heinrichs, M. Articles by Hellhammer, D. H.

Effects of Suckling on Hypothalamic-Pituitary-Adrenal Axis Responses to Psychosocial Stress in Postpartum Lactating Women

Center for Psychobiological and Psychosomatic Research, University of Trier (M.H., G.M., S.W., D.H.H.), D-54286 Trier, Germany; Department of Clinical Psychology, University of Zurich (M.H., U.E.), CH-8044 Zurich, Switzerland; Department of Zoology, University of Regensburg (I.N.), D-93040 Regensburg, Germany; and Institute of Experimental Psychology II, University of Dusseldorf (C.K.), D-40225 Dusseldorf, Germany

Address all correspondence and requests for reprints to: Dr. Markus Heinrichs, Department of Clinical Psychology, University of Zurich, Zurichbergstrasse 43, CH-8044 Zurich, Switzerland. E-mail: mhein{at}klipsy.unizh.ch

Abstract

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.

EVIDENCE FROM ANIMAL and human studies has suggested that suckling is associated with significant alterations in the reactivity of the hypothalamic-pituitaryadrenal (HPA) axis during the postpartum period (1, 2). Observations in the lactating rat have shown an endocrine hyporesponsiveness to physical and psychological stressors, including attenuated secretion of ACTH (3, 4, 5, 6, 7), corticosterone (3, 4, 5, 8, 9, 10, 11), catecholamines (12), oxytocin (9, 13, 14, 15), and PRL (12, 16).

In humans, the effect of lactation on stress-responsive neurohormonal systems has been explored, to date, only for treadmill exercise. Altemus and associates (17) found significantly attenuated plasma ACTH, cortisol, and glucose responses to physical stress in lactating compared with nonlactating women. However, the effects of suckling on endocrine as well as behavioral responses to a psychosocial stress paradigm in humans have not yet been investigated. More important, it is not known whether the marked blunting of endocrine stress responsiveness can be ascribed to suckling as a short-term effect or to lactation in general.

In lactating women, suckling increases both oxytocin and PRL release and decreases plasma levels of ACTH and cortisol, suggesting an inhibitory influence of lactogenic peptides on the HPA axis (8, 18, 19, 20). In addition, systemic administration of exogenous oxytocin decreased basal as well as pharmacologically stimulated ACTH and cortisol plasma levels in healthy humans (21, 22, 23, 24, 25, 26, 27, 28, 29, 30). Notably, suckling results not only in peripheral (31, 32), but also in intracerebral release of oxytocin (33, 34, 35). An inhibitory effect of brain oxytocin on basal and stress-induced HPA axis activity has recently been described in rats (36).

The present study was undertaken to determine the effects of suckling on the HPA axis and the sympathetic-adrenal-medullary system responses to a brief psychosocial stress exposure compared with those in lactating women who were only holding their infants before the stressor. By this means, both groups ensure a similar basal endocrine pattern related to lactation to investigate the acute effect of suckling on stress responsiveness. For mental stress challenging, we employed the Trier Social Stress Test (37), which was repeatedly found to be a potent psychosocial stressor (38, 39, 40, 41).

Subjects and Methods

Subjects

Forty-three healthy lactating women (mean ± SEM age, 30.8 ± 0.7 yr) participated in the study. Subjects were 7.9 ± 0.2 wk postpartum (mean ± SEM) with 30.2% 6–7 wk, 37.2% 8 wk, and 32.6% 9–11 wk postpartum. Subjects were recruited by local advertisements for paid participation in a study of lactation and stress. Participants underwent a medical examination and a diagnostic interview before entering the study and they were considered eligible if they were free of chronic diseases, mental disorders, medication, smoking, and drug or alcohol abuse. All women had uncomplicated pregnancy, and they all delivered full-term, healthy infants by the vaginal route. They were exclusively breast-feeding every 3–4 h on demand by the infant. No subjects had resumed menses before the experimental session. Subjects were instructed to consume their normal food and drink and to abstain from caffeine, alcohol, and running or other strenuous activity during the 24 h before the experiment. The study protocol was approved by the ethics committee of the University of Trier, and all volunteers gave written informed consent for participation in the study.

Experimental protocol

Two weeks before the experiment subjects were instructed in writing either to breast-feed their infants 40 min before the appointment (100 min before the stress procedure) or in a private room in the laboratory 30 min before the stress test. The women were randomly assigned to the breast-feeding or holding group. Further, they were asked to bring somebody with them to care for the infant for about 100 min during the experiment. All subjects with their infants and the accompanying persons reported to the laboratory at 1400 h. On arrival, all participants had a catheter inserted in a brachial vein 45 min before the psychosocial stress procedure. In the following 15-min resting period, subjects completed questionnaires on trait anxiety and depression as well as mood and state anxiety (see below). After this, the first blood and saliva samples were collected at -30 min. According to the aforementioned randomly assigned groups, participants then were instructed either to breast-feed their infants (BF) or to hold their infants without feeding them (HD) during the following 15-min period. Because the mothers were breast-feeding their infants at intervals of 3–4 h and the experimental session lasted 150 min, both the women who fed their infants 40 min before arrival at the laboratory as well as the woman who were instructed so as to feed their infants during the experimental session were scheduled so as to avoid interfering with the mother-infant feeding interval. Breast-feeding 30 min before the start of the stress procedure ensured similar peripheral baseline levels for oxytocin and PRL in both groups immediately before stress. Thereafter, the mothers handed over their infants to the accompanying person who took care of the infant the following 100 min. A second blood and saliva sample was then obtained at -10 min. After additional completion of questionnaires measuring mood and state anxiety, subjects were given instructions about the stress test between -5 and -1 min, and a third blood and saliva sample was collected immediately before the stressor at -1 min. Thereafter, subjects were exposed to the Trier Social Stress Test (37), which primarily consists of an unprepared speech and mental arithmetic performed in front of an audience. Previous studies indicated that this stress protocol reliably induces a significant activation of the HPA axis, with 2- to 3-fold increases in free cortisol as well as cardiovascular and subjective responses indicative of moderate stress in healthy individuals (38, 39, 40, 41). Due to the well known phenomenon that repeated exposure to stressful stimulation has been reported to result in rapid habituation of HPA axis responses, a cross-over study design with the same subjects being tested in each experimental situation was not possible. Including introduction to the test, subjects were confronted with the psychosocially stressful situation for a total of 15 min. Then, further blood and saliva samples were collected at 1 min after termination of the stressor, and subjects completed the questionnaires on mood and state anxiety again, followed by visual analog scales (VAS) for measuring the stressfulness of stress exposure. Additional blood samples were obtained 30 and 60 min after the stress test. Further saliva samples were collected 10, 20, 30, 45, and 60 min after cessation of stress.

Blood and saliva sampling

At the beginning of the experiment, blood samples were obtained for single measurements of basal 17ß-E2 and progesterone levels. Additional blood samples were collected before and after the breast-feeding or holding period, as well as directly before starting the stress test for determining ACTH, cortisol, norepinephrine, epinephrine, oxytocin, and PRL. The remaining three blood samples were collected after cessation of stress as described above. Vasopressin was measured 1 min before and 1 min after the stressor. All blood samples were collected on ice in EDTA-coated tubes and centrifuged at 4 C at 5000 rpm for 5 min. Plasma samples were stored at -80 C until assay.

Saliva was collected using Salivette (Sarstedt, Rommelsdorf, Germany) collection devices immediately before and after the breast-feeding or holding period as well as directly before the stress. Six additional saliva samples were obtained after stress induction as reported above. After chewing for about 60 sec, devices were stored at -20 C until required for biochemical analysis. Before assaying for free cortisol, samples were thawed and spun at 3000 rpm for 5 min to obtain 0.5–1.0 ml clear saliva with low viscosity.

Biochemical analyses

ACTH and total plasma cortisol concentrations were determined with a commercial two-site chemiluminescence assay (Nichols Institute Diagnostics, Bad Nauheim, Germany). PRL, 17ß-E2, and progesterone concentrations were measured employing a commercial ELISA kit (IBL, Hamburg, Germany). Norepinephrine and epinephrine concentrations were assayed by HPLC with electrochemical detection, as previously described (42). Oxytocin and vasopressin concentrations were measured in extracted plasma samples by highly sensitive and selective RIAs (for a detailed description, see Ref. 43). The free cortisol concentration in saliva was analyzed using a time-resolved immunoassay with fluorescence detection, as described previously (44). The limits of detection were 0.5 pg/ml for ACTH, 0.5 nmol/liter for saliva cortisol, 0.8 µg/dl for plasma cortisol, 10 pg/ml for norepinephrine, 10 pg/ml for epinephrine, 0.5 pg/ml for oxytocin, 0.5 pg/ml for vasopressin, 2 ng/ml for PRL, 16 pg/ml for E2, and 0.18 ng/ml for progesterone. Inter- and intraassay coefficients of variance were below 12% and 10%, respectively, for all analytes.

Psychological assessment

A mood questionnaire was employed that is especially suited for repeated measures within several minutes or hours (45). Twelve items are rated on a five-point scale, ranking from 1 = not at all to 5 = very strongly. Factor analyses revealed three scales, termed elevated vs. depressed mood, wakefulness vs. sleepiness, and calmness vs. restlessness. Depression and anxiety were assessed by the German versions of the Self-Rating Depression Scale (46) and the State-Trait Anxiety Inventory (47). Mood and state anxiety were assessed at three times: before the breast-feeding or holding period, between that period and the stressor, and after the psychosocial stress test. Fifteen VASs were employed for subjective ratings of perceived stressfulness of the test. VAS ratings were transformed into values between 0 = not at all to 100 = absolutely.

Statistical analyses

Two-way (group and time) ANOVAs for repeated measures were performed to reveal time effects, between-group differences, and the interaction of time and group for each variable of interest. All reported results were corrected by the Greenhouse-Geisser procedure where appropriate (reflected by the degrees of freedom with decimal values). Single time point data were compared using two-tailed t test. To determine where significant differences from baseline hormone levels in groups were occurring, t tests with Bonferroni corrections were applied. Pearson’s correlations were computed for the areas under the individual response curves (AUC). AUCs were calculated using the trapezoid formula, aggregating the three blood and six saliva hormone levels, respectively, after the stress induction relative to the individual baseline concentration before stress. For all analyses, the level of significance was set at 0.05. All results shown are the mean ± SEM.

Results

Physical and psychometric characteristics of the subjects are presented in Table 1. As described in Subjects and Methods, women were randomly assigned to either the BF or HD group according to the 15-min feeding or holding period 30 min before stress exposure. BF and HD did not differ significantly in age and weeks postpartum. There were no differences among groups in basal E2 and progesterone levels. Trait anxiety and depression scores were similar for both groups and were within the general population normal range.

Hormone levels of BF and HD before and after breast-feeding or holding the infants are shown in Table 2. There were no differences in basal hormone levels before the breast-feeding or holding period between both groups of lactating women (all P = NS). Only PRL levels were higher in the holding group [t(33.1) = 2.91; P = 0.006] based on the shorter time interval since their last breast-feeding period (60 min in HD vs. 100 min in BF before the experiment). There were significant decreases in ACTH [F(1, 41) = 21.56; P < 0.001], salivary free cortisol [F(1, 41) = 8.36; P = 0.006], and total plasma cortisol [F(1, 41) = 31.95; P < 0.001] in the combined group of BF and HD. As expected, breast-feeding compared with holding caused significant elevations of PRL concentrations [time effect: F(1, 41) = 6.67; P = 0.013; group by time effect: F(1, 41) = 12.20; P = 0.001]. No significant changes could be observed in norepinephrine, epinephrine, and oxytocin levels in the total group. All hormone levels of BF and HD were similar 10 min after the feeding or holding period (all P = NS).

There was a significant ACTH stress response in the total group during the psychosocial stress test [F(1.4,58.3) = 25.45; P < 0.001] with a peak 1 min after cessation of the stressor. Similarly, salivary free cortisol and total plasma cortisol levels were significantly increased during the stress [free cortisol: F(2.4,96.7) = 13.65; P < 0.001; total cortisol: F(3,123) = 12.61; P < 0.001]. As depicted in Fig. 1B, cortisol levels were highest 20 min after stress exposure with the expected time lag compared with the peak for ACTH. Correlations between ACTH and cortisol stress responses (AUC) were significant, with r = 0.51 (ACTH vs. free cortisol, P < 0.001) and r = 0.44 (ACTH vs. total cortisol, P = 0.003).

View larger version (23K): [in this window] [in a new window]   Figure 1. Mean ACTH (A), salivary free cortisol (B), total plasma cortisol (C), norepinephrine (D), epinephrine (E), oxytocin (F), and PRL (G) levels (±SEM) before and after exposure to the Trier Social Stress Test in lactating women after breast-feeding (•) and holding () their infants. The shaded areas indicate the period of stress exposure.

As shown in Fig. 1, no significant differences in baseline ACTH, salivary free cortisol, total plasma cortisol, norepinephrine, epinephrine, oxytocin, and PRL levels were observed between BF and HD 1 min before stress (all P = NS). Although PRL baselines may visually appear to differ between groups, post-hoc analyses indicated no significant difference. However, there was a main effect of subject group on cortisol [free cortisol: F(1, 41) = 4.15; P = 0.048; total cortisol: F(1, 41) = 7.75; P = 0.008], with blunted cortisol levels in BF compared with HD. The mean absolute increases in salivary cortisol and plasma cortisol were 6.0 nmol/liter and 3.0 µg/dl, respectively, in HD and 2.4 nmol/liter and 0.7 µg/dl, respectively, in BF. HD showed significant higher free cortisol levels at 10, 20, 30, and 45 min as well as higher plasma cortisol levels 1 and 30 min after cessation of stress compared with baseline (all P < 0.001), whereas in BF no cortisol increases after stress compared with baseline concentrations occurred (all P = NS). Breast-feeding women demonstrated a significant suppression of total plasma cortisol responses [group by time effect: F(3,123) = 5.09; P = 0.002] and a trend toward suppressed salivary free cortisol levels [group by time effect: F(2.4,96.7) = 2.65; P = 0.067] compared with the holding group. Differences in ACTH levels between both groups did not reach statistical significance [F(3,123) = 1.87; P = 0.138].

PRL levels steadily decreased after cessation of psychosocial stress in the breast-feeding women, with an interaction between subject group and PRL concentration after stress [F(1.4,55.6) = 7.31; P = 0.005]. There were no differences between BF and HD in patterns of norepinephrine, epinephrine, and oxytocin changes during the stress test (all P = NS).

Psychometric parameters

Mood and anxiety were assessed before the breast-feeding and holding periods, respectively, as well as before and after the following psychosocial stress test. There was a main effect of subject group on mood [F(1, 41) = 4.87; P = 0.033], with elevated mood in breast-feeding women. In the scale calmness vs. restlessness, feeding increased calmness and composure, whereas holding the infant resulted in elevated tension and feelings of unrest [group by time effect: F(1, 41) = 6.41; P = 0.015]. Scores in the scale wakefulness vs. sleepiness remained unchanged.

Stress exposure worsened mood in both the BF and HD groups [F(1, 41) = 15.42; P < 0.001]. Similarly, the scale calmness vs. restlessness revealed a significant increase in tension and feelings of unrest in response to stress in the total group [F(1, 41) = 11.61; P = 0.001]. Again, no changes in the scale wakefulness vs. sleepiness were observed.

Both breast-feeding as well as holding the infant led to significantly decreased state anxiety responses of BF and HD [F(1, 41) = 4.21; P = 0.047], with a stronger decrease following breast-feeding (BF: before, 36.3 ± 1.8; after, 33.5 ± 1.5; HD: before, 37.1 ± 1.5; after, 36.9 ± 1.5) that did not reach statistical significance [group by time effect: F(1, 41) = 2.90; P = 0.096].

In contrast, state anxiety significantly increased in response to the psychosocial stress test in the combined group [F(1, 41) = 21.08; P < 0.001] with no significant difference among groups. No group differences in VAS ratings of perceived stressfulness were observed.

Discussion

This is the first study to investigate the longer-term (holding group) as well as the short-term (breast-feeding group) effects of suckling on endocrine and behavioral responses to psychosocial stress in lactating women. The Trier Social Stress Test activated the HPA axis as well as the sympathetic-adrenal-medullary system and worsened mood, calmness, and anxiety in the total group. The present results show that salivary free cortisol and total plasma cortisol responses to the stress protocol were markedly blunted in lactating women who were breast-feeding 30 min before stress exposure compared with those who were only holding their infants 30 min before stress (time interval to the last breast-feeding period before stress induction, 100 min). However, the reduction in ACTH stress responses in breast-feeding women did not reach statistical significance.

In lactating rats as well as in lactating women, neuroendocrine responses to stress are known to be reduced, and lactogenic peptides released not only into the blood but also within the brain during suckling may modulate the activity of the HPA axis (4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 36). Besides the potential inhibitory effects of oxytocin at the adrenal level described by Legros and associates (27) in healthy men, inhibition of the basal and stress-induced activity of the HPA axis by intracerebral oxytocin has been demonstrated in both male (48) and female rats (36, 49). Oxytocin release in the hypothalamic paraventricular nucleus and in extrahypothalamic brain regions (e.g. septum) has not only been shown during suckling in both lactating rats (34, 35) and lactating sheep (50), but also in response to an emotional stressor in male rats (51). Because oxytocin was at baseline in both groups at the start of the stress test, and no changes in oxytocin concentrations after stress were observed, plasma oxytocin levels do not seem to mediate the suppression of cortisol stress responses at the adrenal level in the present study. The inhibitory effect of oxytocin on HPA axis responsiveness points to a more central change and could, in fact, be localized in the paraventricular nucleus and the septum, as shown in rats (48).

Furthermore, PRL, significantly released into the blood during suckling, is known to inhibit HPA axis reactivity (8). Interestingly, PRL passes the blood-brain barrier via selective uptake by choroid plexus receptors and exerts central nervous effects (52). Within this context, it is noteworthy to mention that PRL receptors within various hypothalamic and limbic brain regions are up-regulated during lactation (53), although intracerebral release of PRL, e.g. in response to suckling, has not been demonstrated.

In the present study a strong decline in PRL levels occurred after cessation of the stressor in the breast-feeding compared with the holding group. Interestingly, a gradual decrease in plasma PRL levels after stress has also been observed in the lactating rat (12, 16) and in lactating women (17), whereas PRL levels increased in nonlactating animals and humans. In light of these findings, it may be speculated that the prolonged decrease observed in the present study might not only be due to the cessation of suckling, but could also represent a specific response to the mental stressor. Only recently have animal studies revealed support for a prolonged decline in PRL levels after psychological stress in lactating rats (7, 54). Further animal and human studies are needed to determine the role of PRL on stress responsiveness during lactation. Thus, it is possible that the attenuated HPA axis response to the psychosocial stress protocol found in lactating women who were breast-feeding their infants before stress exposure is due to the inhibitory effect of both oxytocin and PRL released into the blood and into distinct brain regions.

Moreover, evidence from animal research has suggested that the increased pulsatile secretion of corticosterone reflecting the effect of suckling during lactation (55, 56) might lead to increased negative feedback on the HPA axis (4, 5). Adaptations of HPA axis activity in the peripartum period occur at all brain levels, including reduction in the activity of hypothalamic CRF neurons (57), reduced excitatory inputs to these neurons (58, 59), and reduced CRF binding at the adenohypophysis (3) to name a few. These adaptations are reversible upon weaning (7).

There were no differences between groups in levels of ACTH and cortisol before the breast-feeding or holding period 30 min before the stress procedure and no differences in baseline levels 1 min before the onset of the stressor. It is important to note that not only breast-feeding women but also women who were only holding their infant showed significant decreases in ACTH, free cortisol, and total plasma cortisol before stress during the suckling and holding periods, respectively. This might be interpreted as due to a decrease in HPA axis hormones after the implantation of the venous catheter 15 min before the breast-feeding or holding period. A further interpretation might be a suckling-related classical conditioning of the HPA axis response in lactating women under the close presence of the infant. In addition, both breast-feeding as well as holding the infant led to significantly decreased anxiety, whereas mood and calmness improved only in the breast-feeding group. However, stress exposure worsened mood and led to an increase in tension, restlessness, and anxiety to a similar extent in both groups of lactating women. These findings agree with data from animal research in which lactating rats showed normal behavioral reactivity to a psychological stress with no statistically significant activation of the HPA axis (4, 6, 7).

The present findings are in accord with a previous report by Altemus et al. (17) showing decreasing PRL concentrations and increasing ACTH, cortisol, norepinephrine, and epinephrine concentrations in women who were breast-feeding their infants 60 min before the start of a physical stressor (treadmill exercise). Also, the researchers found no changes in oxytocin levels. Whereas Altemus and associates (17) investigated the general effect of lactation on endocrine stress responsiveness comparing lactating and nonlactating women, the present study was undertaken to determine the acute effects of suckling (short-term vs. longer-term effects) on endocrine and behavioral responses to psychosocial stress during lactation. In this respect, the present study might extend the findings of Altemus and associates (17) to the sensitive time period for suckling-induced endocrine stress hyporesponsiveness in humans.

In conclusion, the salient result from the present study is that suckling is suggested to exert a short-term suppression of the HPA axis response to mental stress. Thus, lactation in women does not result in a general restraint of the HPA axis response to psychosocial stress. Whereas in animal research it is generally believed that HPA axis hyporesponsiveness can be observed during the whole period of lactation (7), the present data strongly suggest that the blunted adrenocortical stress response in women seems to be counterbalanced if the acute psychosocial stressor occurs 2 h after suckling. The neurobiological mechanisms mediating reduced stress responsivity in lactating women remain to be determined. From an evolutionary-biological point of view, short-term attenuation of cortisol stress responses appear to have several protective functions (17), such as isolating the mother from distracting stimuli of the environment, facilitating the immune system of lactating women, protecting the infant against stress-related high cortisol concentrations in the milk, and preventing inhibition of lactation caused by stress. Future work is needed to determine the short- and long-term effects of breast-feeding in humans in relation to different kinds of stressors.

Acknowledgments

We are grateful to Jutta Bennecke, Mathias Boeck, Ulrike Bucerius, Katrin Burmeister, Helen Esser, Jens Langer, Patrick Mayer, Eva Poll, Miriam Seng, and Silke Welter for excellent research assistance, and to our volunteers for participating in this study. We thank Urs Nater and Marc Simon for preparing the manuscript.

Footnotes

Abbreviations: AUC, Area under the curve; BF, breast-feeding; HD, holding infants without feeding; HPA, hypothalamic-pituitary-adrenal; VAS, visual analog scales.

Received March 7, 2001.

Accepted June 15, 2001.

References

1. Carter CS, Altemus M 1997 Integrative functions of lactational hormones in social behavior and stress management. Ann NY Acad Sci 807:164–174[Abstract/Free Full Text]
2. Lightman SL 1993 Alterations in hypothalamic-pituitary responsiveness during lactation. Ann NY Acad Sci 689:340–346
3. Neumann ID, Johnstone HA, Hatzinger M, et al. 1998 Attenuated neuroendocrine responses to emotional and physical stressors in pregnant rats involve adenohypophysial changes. J Physiol 508:289–300[Abstract/Free Full Text]
4. Stern JM, Goldman L, Levine S 1973 Pituitary-adrenal responsiveness during lactation in rats. Neuroendocrinology 12:179–191[Medline]
5. Walker CD, Lightman SL, Steele MK, Dallman MF 1992 Suckling is a persistent stimulus to the adrenocortical system of the rat. Endocrinology 130:115–125[Abstract]
6. Walker CD, Trottier G, Rochford J, Lavallée D 1995 Dissociation between behavioral and hormonal responses to the forced swim stress in lactating rats. J Neuroendocrinol 7:615–622[CrossRef][Medline]
7. Windle RJ, Wood S, Shanks N, et al. 1997 Endocrine and behavioural responses to noise stress: comparison of virgin and lactating female rats during non-disrupted maternal activity. J Neuroendocrinol 9:407–414[CrossRef][Medline]
8. Schlein PA, Zarrow MX, Denenberg VH 1974 The role of prolactin in the depressed or ‘buffered’ adrenocorticosteroid response of the rat. J Endocrinol 62:93–99[Medline]
9. Lightman SL, Young WS 1989 Lactation inhibits stress-mediated secretion of corticosterone and oxytocin and hypothalamic accumulation of corticotropin-releasing factor and enkephalin messenger ribonucleic acids. Endocrinology 124:2358–2364[Abstract]
10. Stern JM, Levine S 1974 Psychobiological aspects of lactation in rats. Prog Brain Res 41:433–444[Medline]
11. Thoman EB, Conner RL, Levine S 1970 Lactation suppresses adrenal corticosteroid activity and aggressiveness in rats. J Comp Physiol Psychol 70:364–369[CrossRef][Medline]
12. Higuchi T, Negoro H, Arita J 1989 Reduced responses of prolactin and catecholamine to stress in the lactating rat. J Endocrinol 122:495–498[Abstract]
13. Carter DA, Lightman SL 1987 Oxytocin responses to stress in lactating and hyperprolactinaemic rats. Neuroendocrinology 46:532–537[Medline]
14. Higuchi T, Honda K, Takano S, Negoro H 1988 Reduced oxytocin response to osmotic stimulus and immobilization stress in lactating rats. J Endocrinol 116:225–230[Abstract]
15. Neumann I, Landgraf R, Bauce L, Pittman QJ 1995 Osmotic responsiveness and cross talk involving oxytocin, but not vasopressin or amino acids, between the supraoptic nuclei in virgin and lactating rats. J Neurosci 15:3408–3417[Abstract]
16. Banky Z, Nagy GM, Halasz B 1994 Analysis of pituitary prolactin and adrenocortical response to ether, formalin or restraint in lactating rats: rise in corticosterone, but no increase in plasma prolactin levels after exposure to stress. Neuroendocrinology 59:63–71[Medline]
17. Altemus M, Deuster PA, Galliven E, Carter CS, Gold PW 1995 Suppression of hypothalamic-pituitary-adrenal axis responses to stress in lactating women. J Clin Endocrinol Metab 80:2954–2959[Abstract/Free Full Text]
18. Amico JA, Johnston JM, Vagnucci AH 1994 Suckling-induced attenuation of plasma cortisol concentrations in postpartum lactating women. Endocr Res 20:79–87[Medline]
19. Chiodera P, Salvarani C, Bacchi-Modena A, et al. 1991 Relationship between plasma profiles of oxytocin and adrenocorticotropic hormone during suckling or breast stimulation in women. Horm Res 35:119–123[Medline]
20. Nissen E, Uvnäs-Moberg K, Svensson K, Stock S, Widstrom AM, Winberg J 1996 Different patterns of oxytocin, prolactin but not cortisol release during breastfeeding in women delivered by caesarean section or by the vaginal route. Early Hum Dev 45:103–118[CrossRef][Medline]
21. Chiodera P, Coiro V 1987 Oxytocin reduces metyrapone-induced ACTH secretion in human subjects. Brain Res 420:178–181[CrossRef][Medline]
22. Coiro V, Chiodera P, Rossi G, et al. 1985 Effect of naloxone on oxytocin-induced cortisol decrease in normal men. Acta Endocrinol (Copenh) 108:261–265[Medline]
23. Coiro V, Passeri M, Davoli C, et al. 1988 Oxytocin reduces exercise-induced ACTH and cortisol rise in man. Acta Endocrinol (Copenh) 119:405–412[Medline]
24. Legros JJ, Chiodera P, Demey-Ponsart E 1982 Inhibitory influence of exogenous oxytocin on adrenocorticotropin secretion in normal human subjects. J Clin Endocrinol Metab 55:1035–1039[Abstract]
25. Legros JJ, Chiodera P, Geenen V, Smitz S, von Frenckell R 1984 Dose-response relationship between plasma oxytocin and cortisol and adrenocorticotropin concentrations during oxytocin infusion in normal men. J Clin Endocrinol Metab 58:105–109[Abstract]
26. Legros JJ, Chiodera P, Geenen V, von Frenckell R 1987 Confirmation of the inhibitory influence of exogenous oxytocin on cortisol and ACTH in man: evidence of reproducibility. Acta Endocrinol (Copenh) 114:345–349[Medline]
27. Legros JJ, Chiodera P, Geenen V 1988 Inhibitory action of exogenous oxytocin on plasma cortisol in normal human subjects: evidence of action at the adrenal level. Neuroendocrinology 48:204–206[Medline]
28. Page SR, Ang VT, Jackson R, White A, Nussey SS, Jenkins JS 1990 The effect of oxytocin infusion on adenohypophyseal function in man. Clin Endocrinol (Oxf) 32:307–313[Medline]
29. Petraglia F, Facchinetti F, d’Ambrogio G, Volpe A, Genazzani AR 1986 Somatostatin and oxytocin infusion inhibits the rise of plasma ß-endorphin, ß-lipotrophin and cortisol induced by insulin hypoglycaemia. Clin Endocrinol (Oxf) 24:609–616[Medline]
30. Suh BY, Liu JH, Rasmussen DD, Gibbs DM, Steinberg J, Yen SS 1986 Role of oxytocin in the modulation of ACTH release in women. Neuroendocrinology 44:309–313[Medline]
31. Higuchi T, Honda K, Fukuoka T, Negoro H, Wakabayashi K 1985 Release of oxytocin during suckling and parturition in the rat. J Endocrinol 105:339–346[Abstract]
32. Higuchi T, Tadokoro Y, Honda K, Negoro H 1986 Detailed analysis of blood oxytocin levels during suckling and parturition in the rat. J Endocrinol 110:251–256[Abstract]
33. Moos F, Poulain DA, Rodriguez F, Guerne Y, Vincent JD, Richard P 1989 Release of oxytocin within the supraoptic nucleus during the milk ejection reflex in rats. Exp Brain Res 76:593–602[CrossRef][Medline]
34. Neumann I, Ludwig M, Engelmann M, Pittman QJ, Landgraf R 1993 Simultaneous microdialysis in blood and brain: oxytocin and vasopressin release in response to central and peripheral osmotic stimulation and suckling in the rat. Neuroendocrinology 58:637–645[Medline]
35. Neumann I, Landgraf R 1989 Septal and hippocampal release of oxytocin, but not vasopressin, in the conscious lactating rat during suckling. J Neuroendocrinol 1:305–308
36. Neumann ID, Torner L, Wigger A 2000 Brain oxytocin: differential inhibition of neuroendocrine stress responses and anxiety-related behaviour in virgin, pregnant and lactating rats. Neuroscience 95:567–575[Medline]
37. Kirschbaum C, Pirke KM, Hellhammer DH 1993 The ‘Trier Social Stress Test’–a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28:76–81[Medline]
38. Kirschbaum C, Schommer N, Federenko I, et al. 1996 Short-term estradiol treatment enhances pituitary-adrenal axis and sympathetic reponses to psychosocial stress in healthy young men. J Clin Endocrinol Metab 81:3639–3643[Abstract]
39. Kirschbaum C, Bono EG, Rohleder N 1997 Effects of fasting and glucose load on free cortisol responses to stress and nicotine. J Clin Endocrinol Metab 82:1101–1105[Abstract/Free Full Text]
40. Kirschbaum C, Kudielka BM, Gaab J, Schommer NC, Hellhammer DH 1999 Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosom Med 61:154–162[Abstract/Free Full Text]
41. Kudielka BM, Hellhammer J, Hellhammer DH, et al. 1998 Sex differences in endocrine and psychological responses to psychosocial stress in healthy elderly subjects and the impact of a 2-week dehydroepiandrosterone treatment. J Clin Endocrinol Metab 83:1756–1761[Abstract/Free Full Text]
42. Smedes F, Kraak JC, Poppe H 1982 Simple and fast solvent extraction system for selective and quantitative isolation of adrenaline, noradrenaline and dopamine from plasma and urine. J Chromatogr 231:25–39[Medline]
43. Landgraf R 1981 Simultaneous measurement of arginine vasopressin and oxytocin in plasma and neurohypophyses by radioimmunoassay. Endokrinologie 78:191–204[Medline]
44. Dressendörfer RA, Kirschbaum C, Rohde W, Stahl F, Strasburger CJ 1992 Synthesis of a cortisol-biotin conjugate and evaluation as tracer in an immunoassay for salivary cortisol measurement. J Steroid Biochem Mol Biol 43:683–692[CrossRef][Medline]
45. Steyer R, Schwenkmezger P, Notz P, Eid M 1997 Der Mehrdimensionale Befindlichkeitsfragebogen (MDBF). Göttingen: Hogrefe
46. Zung WWK 1965 A self-rating depression scale. Arch Gen Psychiatry 12:63–70
47. Spielberger CD, Gorsuch RL, Lushene RE 1970 Manual for the State-Trait Anxiety Inventory (STAI). Palo Alto: Consulting Psychologists Press
48. Neumann ID, Krömer SA, Toschi N, Ebner K 2000 Brain oxytocin inhibits the (re)activity of the hypothalamo-pituitary-adrenal axis in male rats: involvement of hypothalamic and limbic brain regions. Regul Pept 96:31–38[CrossRef][Medline]
49. Windle RJ, Shanks N, Lightman SL, Ingram CD 1997 Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats. Endocrinology 138:2829–2834[Abstract/Free Full Text]
50. Kendrick KM, Keverne EB 1992 Control of synthesis and release of oxytocin in the sheep brain. Ann NY Acad Sci 652:102–121[Medline]
51. Ebner K, Wotjak CT, Landgraf R, Engelmann M 2000 A single social defeat experience selectively stimulates the release of oxytocin, but not vasopressin, within the septal brain area of male rats. Brain Res 872:87–92[CrossRef][Medline]
52. Torner L, Toschi N, Pohlinger A, Landgraf R, Neumann ID 2001 Anxiolytic and anti-stress effects of brain prolactin: improved efficacy of antisense targeting of the prolactin receptor by molecular modeling. J Neurosci 21:3207–3214[Abstract/Free Full Text]
53. Pi, X, Grattan, DR 1999 Increased prolactin receptor immunoreactivity in the hypothalamus of lactating rats. J Neuroendocrinol 11:693–705[CrossRef][Medline]
54. Neumann ID, Toschi N, Ohl F, Torner L, Krömer SA 2001 Maternal defense as an emotional stressor in female rats: correlation of neuroendocrine and behavioural parameters and involvement of brain oxytocin. Eur J Neurosci 13:1–10[CrossRef][Medline]
55. Neville MC, Berga SE 1983 Cellular and molecular aspects of the hormonal control of mammary function. In: Neville MC, Neifert MR, eds. Lactation: physiology, nutrition and breast feeding. New York: Plenum Press; 141–177
56. van Haasteren GA, van Toor H, Klootwijk W, et al. 1996 Studies on the role of TRH and corticosterone in the regulation of prolactin and thyrotrophin secretion during lactation. J Endocrinol 148:325–336[Abstract]
57. Douglas AJ, Russell JA 1994 Corticotrophin-releasing hormone, proenkephalin A and oxytocin mRNA’s in the paraventricular nucleus during pregnancy and parturition in the rat. Gene Ther 1(Suppl 1):S85
58. Toufexis DJ, Thrivikraman KV, Plotsky PM, Morilak DA, Huang N, Walker CD 1998 Reduced noradrenergic tone to the hypothalamic paraventricular nucleus contributes to the stress hypo-responsiveness of lactation. J Endocrinol 10:417–427
59. Douglas AJ, Johnstone HA, Wigger A, Landgraf R, Russell JA, Neumann ID 1998 The role of endogenous opioids in neurohypophysial and hypothalamo-pituitary-adrenal axis hormone secretory responses to stress in pregnant rats. J Endocrinol 158:285–293[Abstract]

This article has been cited by other articles:

				D. A. Slattery and I. D. Neumann No stress please! Mechanisms of stress hyporesponsiveness of the maternal brain J. Physiol., January 15, 2008; 586(2): 377 - 385. [Abstract] [Full Text] [PDF]

				S M Montgomery, A Ehlin, and A Sacker Breast feeding and resilience against psychosocial stress Arch. Dis. Child., December 1, 2006; 91(12): 990 - 994. [Abstract] [Full Text] [PDF]

				J. F. Paulson, S. Dauber, and J. A. Leiferman Individual and Combined Effects of Postpartum Depression in Mothers and Fathers on Parenting Behavior Pediatrics, August 1, 2006; 118(2): 659 - 668. [Abstract] [Full Text] [PDF]

				A. J. Tilbrook, A. I. Turner, M. D. Ibbott, and I. J. Clarke Activation of the Hypothalamo-Pituitary-Adrenal Axis by Isolation and Restraint Stress during Lactation in Ewes: Effect of the Presence of the Lamb and Suckling Endocrinology, July 1, 2006; 147(7): 3501 - 3509. [Abstract] [Full Text] [PDF]

				I. D. Neumann, L. Torner, N. Toschi, and A. H. Veenema Oxytocin actions within the supraoptic and paraventricular nuclei: differential effects on peripheral and intranuclear vasopressin release Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2006; 291(1): R29 - R36. [Abstract] [Full Text] [PDF]

				A. Nierop, A. Bratsikas, A. Klinkenberg, U. M. Nater, R. Zimmermann, and U. Ehlert Prolonged Salivary Cortisol Recovery in Second-Trimester Pregnant Women and Attenuated Salivary {alpha}-Amylase Responses to Psychosocial Stress in Human Pregnancy J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1329 - 1335. [Abstract] [Full Text] [PDF]

				M. W. Groer Differences Between Exclusive Breastfeeders, Formula-Feeders, and Controls: A Study of Stress, Mood, and Endocrine Variables Biol Res Nurs, October 1, 2005; 7(2): 106 - 117. [Abstract] [PDF]

				G. MASTORAKOS and I. ILIAS Maternal and Fetal Hypothalamic-Pituitary-Adrenal Axes During Pregnancy and Postpartum Ann. N.Y. Acad. Sci., November 1, 2003; 997(1): 136 - 149. [Abstract] [Full Text] [PDF]

				P. D. Hill, R. T. Chatterton Jr., and J. C. Aldag Neuroendocrine Responses to Stressors in Lactating and Nonlactating Mammals: A Literature Review Biol Res Nurs, October 1, 2003; 5(2): 79 - 86. [Abstract] [PDF]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Heinrichs, M. Articles by Hellhammer, D. H. Search for Related Content PubMed PubMed Citation Articles by Heinrichs, M. Articles by Hellhammer, D. H.