The role of prolactin in the suppression of Crh mRNA expression during pregnancy and lactation in the mouse.

Abstract

Maternal stress is associated with negative health consequences for both the mother and her offspring. To prevent these adverse outcomes, activity of the hypothalamic-pituitary-adrenal (HPA) axis is attenuated during pregnancy and lactation. Although the mechanisms generating this adaptive change have not been defined fully, the anterior pituitary hormone prolactin may play a significant role. The present study investigated the role of prolactin in regulating the basal activity of the HPA axis during pregnancy and lactation in the mouse, focussing upon the corticotrophin-releasing hormone (CRH) neurones. Using in situ hybridisation, a decrease in Crh mRNA-expressing cell number in pregnant (55.6±9.0 cells per section) and lactating (97.4±4.9) mice compared to virgin controls was characterised (186.8±18.7, P<.01 Tukey-Kramer test; n=6-7 per group). Removal of the pups (24hours) and thus the associated suckling-induced prolactin secretion, restored CRH neurone number (180.1±19.7). To specifically test the role of prolactin in suppressing Crh mRNA expression in lactation, prolactin levels were selectively manipulated in lactating mice. Lactating mice were treated with ovine prolactin (1500μgday-1 , osmotic minipump, s.c.; n=7) or vehicle (n=6) for 24hours following pup removal. This was sufficient to suppress Crh mRNA expression from 108.0±13.5 to 53.7±16.7 cells per section (P<.05 Student's t-test). Additional cohorts of lactating mice were treated with bromocriptine (300μg over 24hours, s.c.; n=7) or vehicle (n=5) to suppress endogenous prolactin secretion; however, no change in Crh mRNA expression was detected. Thus, although prolactin was sufficient to suppress Crh mRNA expression in the paraventricular nucleus, it does not appear to be required for the ongoing regulation of the CRH neurones in lactation.