Peripartum Hypothalmus-Pituitary-Adrenal axis plasticity and its prevention by high-fat diet intake : Focus on the adrenal gland

For its primary role in the maintenance of body homeostasis, the maternal Hypothalamus-Pituitary-Adrenal (HPA) axis profoundly adapts during pregnancy and lactation. Through basic and human research, several peripartum changes in HPA axis–associated hormonal levels as well as alterations in brain and pituitary morphology and physiology have been already identified. Intriguingly, human and rodent studies demonstrated that dysregulation of the basal- and stress-induced neuroendocrine HPA axis peripartum (re)activity feature in multiple pathologies, among them postpartum depression, anxiety and obesity. Specifically, the previously mentioned illnesses are often characterized by unbalanced basal and stress-induced levels of glucocorticoids and their main secretagogue adrenocorticotropic hormone (ACTH), glucocorticoids that are the major HPA axis peripheral effectors synthesised by and secreted from the adrenal glands; this finding strongly suggests adrenal-mediated mechanisms may play a role. However, to my knowledge, it is unknown if the adrenal glands adapt during the peripartum period, and if so, whether disruption of such changes may contribute to the aetiology of peripartum-associated pathologies. Therefore, with my thesis I aimed to investigate whether the adrenal cholesterol delivery pathways, important component of the steroidogenic machinery, adapt peripartum in rodents and to assess the effect of high-fat diet feeding on adrenal plasticity, HPA axis function and maternal behaviour. Several adrenal adaptations have been highlighted, particularly during lactation. Indeed, I could show that, although adrenal lipid droplets are markedly depleted starting already at mid-pregnancy, all three adrenal cholesterol delivery pathways profoundly adapt at mid-lactation in the rat. Evidence of peripartum-associated plasticity in adrenal cholesterol delivery was reported also in the lactating mouse, although with some discrepancies compared to the rat, suggesting that the adrenal changes reported in the present thesis represent robust peripartum adaptations that may concur to sustain peripartum-associated hormonal fluctuations. Intriguingly, adrenal plasticity was substantially impaired by high-fat diet intake, manipulation that also altered basal and ACTH-induced CORT levels in the lactating rat. The changes in adrenal morphology and HPA axis function were accompanied by behavioural abnormalities with obese mothers showing decreased maternal care the day after parturition and increased anxiety-related behaviour. Importantly, similar behavioural and HPA axis-associated aberrations like impaired mother-infant interaction and altered basal CORT levels are known features of human postpartum pathologies and, therefore, the animal models described in the present thesis may represent valid tools to study their pathophysiological mechanisms. Taken together, the findings reported in the present thesis shed light on adrenal mechanisms that are highly suggested to relate to the “peculiar” HPA axis peripartum function at both, physiological and pathological conditions.