Adaptive Responses of the Maternal Hypothalamic‐Pituitary‐Adrenal Axis during Pregnancy and Lactation

Abstract

Pregnancy and lactation have been shown over the last 40 years to be physiological states in which hypothalamic-pituitary-adrenal (HPA) axis responses to stressors are markedly attenuated (1, 2). These phenomena provide an unequalled opportunity to understand natural mechanisms that reduce stress responses, and the prospect of new therapies for stress-related disorders.The (HPA) axis comprises the corticotropin-releasing factor (CRF) neurones in the parvocellular paraventricular nucleus (pPVN), which also variably produce vasopressin and project to the external zone of the median eminence. These neurosecretory neurones release their peptides into the primary capillary plexus of the hypothalamic-hypophysial portal system to act respectively on the CRF1 and V1b receptors on the corticotrophs in the anterior pituitary gland (3, 4). The consequent stimulation of secretion of corticotropin [adrenocorticotrophic hormone (ACTH); a product of pro-opiomelanocortin (POMC)], leads to increased synthesis and secretion of glucocorticoid (cortisol in humans and other species; corticosterone in rodents) by the adrenal cortex. Glucocorticoids have powerful actions on metabolism and immune mechanisms (5, 6). The HPA axis is regulated by tonic glucocorticoid feedback (7) [involving mineralocorticoid receptors (MR) in the hippocampus, and glucocorticoid receptors (GR) in the brain and corticotrophs], by metabolic signals (8) (including from adipose tissue), and the circadian clock in the suprachiasmatic nuclei (9). Over the past 40 years, it has been recognised that the maternal hypothalamic-pituitary-adrenal (HPA) axis undergoes adaptations through pregnancy and lactation that might contribute to avoidance of adverse effects of stress on the mother and offspring. The extent of the global adaptations in the HPA axis has been revealed and the underlying mechanisms investigated within the last 20 years. Both basal, including the circadian rhythm, and stress-induced adrenocorticotrophic hormone and glucocorticoid secretory patterns are altered. Throughout most of pregnancy, and in lactation, these changes predominantly reflect reduced drive by the corticotropin-releasing factor (CRF) neurones in the parvocellular paraventricular nucleus (pPVN). An accompanying profound attenuation of HPA axis responses to a wide variety of psychological and physical stressors emerges after mid-pregnancy and persists until the end of lactation. Central to this suppression of stress responsiveness is reduced activation of the pPVN CRF neurones. This is consequent on the reduced effectiveness of the stimulation of brainstem afferents to these CRF neurones (for physical stressors) and of altered processing by limbic structures (for emotional stressors). The mechanism of reduced CRF neurone responses to physical stressors in pregnancy is the suppression of noradrenaline release in the PVN by an up-regulated endogenous opioid mechanism, which is induced by neuroactive steroid produced from progesterone. By contrast, in lactation suckling the young provides...

Reproductive rate, not dominance status, affects fecal glucocorticoid levels in breeding female meerkats

“…Even during the first week of late pregnancy, fGC levels already averaged~200 ng/g feces and levels of up to~400 ng/g feces were common; with this rising tõ 1000 ng/g feces in some females by the start of the final third of gestation. That all our females carried to term despite high levels of fGC, in conjunction with known reduced sensitivity of maternal HPA axis to stressors toward parturition in other species (Brunton et al, 2008;Douglas et al, 2003;Johnstone et al, 2000), suggests that further work is required to test the link between adrenal activity and abortions.…”

“…First, during gestation, GCs can arise from both maternal and feto-placental sources, with the relative contribution by the latter increasing as pregnancy proceeds (deM Fencl et al, 1980;Keller-Wood and Wood, 2001;Ilias, 2000, 2003;Waddell, 1993). However, it is not unusual for the fetoplacental unit to have little impact on maternal GCs levels, as is the case in rodents (Brunton et al, 2008). If feto-placental sources of GCs contribute significantly to maternal fGC levels in meerkats, we would expect fGC to peak at parturition.…”

“…This is compounded by the fact that most previous studies have been conducted during non-breeding periods to avoid the confounding effects of increased adrenal activity during breeding (Brunton et al, 2008;Dantzer et al, 2010;Krasnow and Steiner, 2006;Mastorakos and Ilias, 2003;Trainer, 2002). Longitudinal studies making use of non-invasive assessments of GCs excretion across breeding and nonbreeding periods are now required to clarify patterns of natural variation (Bonier et al, 2009;Dingemanse et al, 2010).…”

Efectos neurobiológicos del estrés prenatal sobre el nuevo ser

“…Por otra parte, la expresión placentaria de 11-beta hidroxiesteroide deshidrogenasa tipo 2, limita la exposición fetal a los glucocorticoides maternos a través de la metabolización de corticosterona en 11-dehidrocorticosterona, un metabolito inactivo 32 . Si bien la exposición reiterada a estrés en el embarazo reduce significativamente la actividad de esta enzima en la barrera placentaria y su expresión génica 33,34 , debe considerarse también que las respuestas del eje HHA materno en situaciones estresantes se reducen drásticamente al final del embarazo, lo que supone minimizar la transmisión de glucocorticoides hacia el feto 34 .…”

The Emotional and Hormonal Pathways of Labour and Birth: Integrating Mind, Body and Behaviour.

“…There is a complex set of interactions between the hypothalamus, the pituitary and the adrenal glands (HPA axis). CRH is released from the hypothalamus and travels to the anterior pituitary to orchestrate an integrated stress response (Brunton, Russell, & Douglas, 2008: Grammatopoulos, 2008. It stimulates the release of beta-endorphin and adrenocorticotropin hormone (ACTH).…”