Suppression of basal HPA axis activity in the late pregnant and lactating mouse. — ASN Events

Suppression of basal HPA axis activity in the late pregnant and lactating mouse. (#241)

Papillon Gustafson 1 , Stephen Bunn 1 , Dave Grattan 1
  1. University of Otago, Dunedin Central, OTAGO, New Zealand

Stress during pregnancy and lactation is associated with increased post-partum maternal anxiety, impaired lactation, and the development of an anxiety phenotype in the offspring. To avoid these outcomes, the activity of the hypothalamic-pituitary-adrenal (HPA) axis, a mediator of the stress response, is attenuated at this time. The mechanism generating this change is not known; however, the anterior pituitary hormone prolactin may play a significant role firstly, because its circulating levels increase across pregnancy and lactation and secondly, it mediates other important adaptations within the maternal brain. This project aimed to investigate the basal (non-stressed) activity of the HPA axis during pregnancy and lactation in the mouse, focussing specifically upon the hypothalamic corticotropin-releasing hormone (CRH) neurons.  In situ hybridisation was used to characterise CRH mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus of pregnant (Day 18; n=7), lactating (Day 7; n=7) and pup-deprived (24 h) lactating (Day 7; n=7) mice in comparison to virgin controls (n=6). The density of CRH mRNA expression in the PVN of pregnant and lactating mice was significantly reduced in comparison to controls (36.5 ± 6.8% and 47.4 ± 5.7%, respectively; P<0.001, one-way ANOVA with a Bonferroni’s posthoc test). Removal of the pups, and thus the associated suckling-induced prolactin secretion, restored CRH mRNA expression to levels not significantly different from controls (75.1 ± 5.3%). Quantification of CRH neuron number in the PVN revealed similar trends, with significant reductions observed in both pregnant (49.6 ± 9.3) and lactating (53.6 ± 4.9) mice in comparison to controls (158.2 ± 21.5, P<0.0001), while pup-deprivation provided a partial restoration of neuron number (107.6 ± 9.4, P<0.05). These results show that basal HPA axis activity is suppressed in late pregnant and lactating mice and suggest a potential role for prolactin in mediating its attenuated activity observed at this time.