ABSTRACT
The regulation of the activity of the hypothalamic-pituitary-adrenal (HPA) axis is modified during lactation, wherein a blunted stress-induced adrenocorticotropic hormone (ACTH) and glucocorticoid secretion is coupled with elevated basal secretion of these hormones. The involvement of pituitary modifications in lactation-induced stress hyporesponsiveness has yet to be established. In this study we tested the hypothesis that the pituitary sensitivity to corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) is altered in lactation in the rat. We examined the effect of exogenous CRF (0.1-5 microg/rat), AVP (0.01-0.5 microg/rat), and AVP (0.01-0.5 microg/rat)+CRF (0.1 microg/rat) on the ACTH response of virgin, mid-lactating (lactation day 10-12) females, as well as nursing females separated from their pups for 48 h. Additionally, to determine if changes in CRF- or AVP-receptor densities might mediate alterations in pituitary sensitivity, we compared pituitary CRF- and AVP-receptor binding by autoradiography in pregnant, mid-lactating, and virgin female rats. While both virgin and lactating female rats exhibited significant ACTH responses to CRF, the responses to the highest doses of CRF (2.0 and 5.0 microg/rat) were greater in virgin than in lactating females. Separation of the litter for 48 h partially restored pituitary responsiveness to 2.0 microg of CRF. Conversely, whereas lactating females displayed robust ACTH secretion following a high dose of AVP or following a combination of AVP+CRF, the response of virgin females was much smaller. These modifications in pituitary responsiveness were not accompanied by significant differences in pituitary CRF-and AVP-receptors levels between female groups. Our results demonstrate that a reduction in pituitary sensitivity to CRF, but not to AVP occur during lactation in the rat which mediates, at least in part, the stress hyporesponsiveness of lactation.
