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      Adaptive Modifications of Maternal Hypothalamic-Pituitary-Adrenal Axis Activity during Lactation and Salsolinol as a New Player in this Phenomenon

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      International Journal of Endocrinology
      Hindawi

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          Abstract

          Both basal and stress-induced secretory activities of the hypothalamic-pituitary-adrenal (HPA) axis are distinctly modified in lactating females. On the one hand, it aims to meet the physiological demands of the mother, and on the other hand, the appropriate and stable plasma cortisol level is one of the essential factors for the proper offspring development. Specific adaptations of HPA axis activity to lactation have been extensively studied in several animal species and humans, providing interesting data on the HPA axis plasticity mechanism. However, most of the data related to this phenomenon are derived from studies in rats. The purpose of this review is to highlight these adaptations, with a particular emphasis on stress reaction and differences that occur between species. Existing data on breastfeeding women are also included in several aspects. Finally, data from the experiments in sheep are presented, indicating a new regulatory factor of the HPA axis—salsolinol—which typical role was revealed in lactation. It is suggested that this dopamine derivative is involved in both maintaining basal and suppressing stress-induced HPA axis activities in lactating dams.

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          Regulation of the Hypothalamic-Pituitary-Adrenocortical Stress Response.

          The hypothalamo-pituitary-adrenocortical (HPA) axis is required for stress adaptation. Activation of the HPA axis causes secretion of glucocorticoids, which act on multiple organ systems to redirect energy resources to meet real or anticipated demand. The HPA stress response is driven primarily by neural mechanisms, invoking corticotrophin releasing hormone (CRH) release from hypothalamic paraventricular nucleus (PVN) neurons. Pathways activating CRH release are stressor dependent: reactive responses to homeostatic disruption frequently involve direct noradrenergic or peptidergic drive of PVN neurons by sensory relays, whereas anticipatory responses use oligosynaptic pathways originating in upstream limbic structures. Anticipatory responses are driven largely by disinhibition, mediated by trans-synaptic silencing of tonic PVN inhibition via GABAergic neurons in the amygdala. Stress responses are inhibited by negative feedback mechanisms, whereby glucocorticoids act to diminish drive (brainstem) and promote transsynaptic inhibition by limbic structures (e.g., hippocampus). Glucocorticoids also act at the PVN to rapidly inhibit CRH neuronal activity via membrane glucocorticoid receptors. Chronic stress-induced activation of the HPA axis takes many forms (chronic basal hypersecretion, sensitized stress responses, and even adrenal exhaustion), with manifestation dependent upon factors such as stressor chronicity, intensity, frequency, and modality. Neural mechanisms driving chronic stress responses can be distinct from those controlling acute reactions, including recruitment of novel limbic, hypothalamic, and brainstem circuits. Importantly, an individual's response to acute or chronic stress is determined by numerous factors, including genetics, early life experience, environmental conditions, sex, and age. The context in which stressors occur will determine whether an individual's acute or chronic stress responses are adaptive or maladaptive (pathological).
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            Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo–pituitary–adrenocortical responsiveness

            Appropriate regulatory control of the hypothalamo-pituitary-adrenocortical stress axis is essential to health and survival. The following review documents the principle extrinsic and intrinsic mechanisms responsible for regulating stress-responsive CRH neurons of the hypothalamic paraventricular nucleus, which summate excitatory and inhibitory inputs into a net secretory signal at the pituitary gland. Regions that directly innervate these neurons are primed to relay sensory information, including visceral afferents, nociceptors and circumventricular organs, thereby promoting 'reactive' corticosteroid responses to emergent homeostatic challenges. Indirect inputs from the limbic-associated structures are capable of activating these same cells in the absence of frank physiological challenges; such 'anticipatory' signals regulate glucocorticoid release under conditions in which physical challenges may be predicted, either by innate programs or conditioned stimuli. Importantly, 'anticipatory' circuits are integrated with neural pathways subserving 'reactive' responses at multiple levels. The resultant hierarchical organization of stress-responsive neurocircuitries is capable of comparing information from multiple limbic sources with internally generated and peripherally sensed information, thereby tuning the relative activity of the adrenal cortex. Imbalances among these limbic pathways and homeostatic sensors are likely to underlie hypothalamo-pituitary-adrenocortical dysfunction associated with numerous disease processes.
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              Prenatal Stress, Glucocorticoids and the Programming of Adult Disease

              Numerous clinical studies associate an adverse prenatal environment with the development of cardio-metabolic disorders and neuroendocrine dysfunction, as well as an increased risk of psychiatric diseases in later life. Experimentally, prenatal exposure to stress or excess glucocorticoids in a variety of animal models can malprogram offspring physiology, resulting in a reduction in birth weight and subsequently increasing the likelihood of disorders of cardiovascular function, glucose homeostasis, hypothalamic–pituitary–adrenal (HPA) axis activity and anxiety-related behaviours in adulthood. During fetal development, placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) provides a barrier to maternal glucocorticoids. Reduced placental 11β-HSD2 in human pregnancy correlates with lower birth weight and higher blood pressure in later life. Similarly, in animal models, inhibition or knockout of placental 11β-HSD2 lowers offspring birth weight, in part by reducing glucose delivery to the developing fetus in late gestation. Molecular mechanisms thought to underlie the programming effects of early life stress and glucocorticoids include epigenetic changes in target chromatin, notably affecting tissue-specific expression of the intracellular glucocorticoid receptor (GR). As such, excess glucocorticoids in early life can permanently alter tissue glucocorticoid signalling, effects which may have short-term adaptive benefits but increase the risk of later disease.
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                Author and article information

                Contributors
                Journal
                Int J Endocrinol
                Int J Endocrinol
                IJE
                International Journal of Endocrinology
                Hindawi
                1687-8337
                1687-8345
                2018
                10 April 2018
                : 2018
                : 3786038
                Affiliations
                Department of Animal Physiology, The Kielanowski Institute of Animal Physiology and Nutrition Polish Academy of Sciences, Instytucka 3, 05-110 Jablonna, Poland
                Author notes

                Academic Editor: Maria L. Dufau

                Author information
                http://orcid.org/0000-0002-2556-4983
                Article
                10.1155/2018/3786038
                5914094
                11f2de10-b68f-47cf-9b53-5433fbd53e8b
                Copyright © 2018 Malgorzata Hasiec and Tomasz Misztal.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 August 2017
                : 21 March 2018
                Funding
                Funded by: Ministerstwo Nauki i Szkolnictwa Wyzszego
                Funded by: National Research Centre
                Award ID: 2012/05/N/NZ9/01581
                Award ID: N N311 082037
                Categories
                Review Article

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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