Altered pituitary sensitivity to corticotropin-releasing factor and arginine vasopressin participates in the stress hyporesponsiveness of lactation in the rat

The regulation of the activity of the hypothalamic-pituitary-adrenal (HPA) axis is modified during lactation, wherein a blunted stress-induced adrenoc orticotropic hormone (ACTH) and glucocorticoid secretion is coupled with el evated basal secretion of these hormones. The involvement of pituitary modi fications in lactation-induced stress hyporesponsiveness has yet to be esta blished. In this study we tested the hypothesis that the pituitary sensitiv ity to corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) is altered in lactation in the rat. We examined the effect of exogenous GRF (0.1-5 mu g/rat), AVP (0.01-0.5 mu g/rat), and AVP (0.01-0.5 mu g/rat) + C RF (0.1 mu g/rat) on the ACTH response of virgin, mid-lactating (lactation day 10-12) females, as well as nursing females separated from their pups fo r 48 h. Additionally, to determine if changes in CRF- or AVP-receptor densi ties might mediate alterations in pituitary sensitivity, we compared pituit ary CRF- and AVP-receptor binding by autoradiography in pregnant, mid-lacta ting, and virgin female rats. While both virgin and lactating female rats e xhibited significant ACTH responses to CRF, the responses to the highest do ses of CRF (2.0 and 5.0 mu g/rat) were greater in virgin than in lactating females. Separation of the litter for 48 h partially restored pituitary res ponsiveness to 2.0 mu g of CRF. Conversely, whereas lactating females displ ayed robust ACTH secretion following a high dose of AVP or following a comb ination of AVP + GRF, the response of virgin females was much smaller. Thes e modifications in pituitary responsiveness were not accompanied by signifi cant differences in pituitary CRF- and AVP-receptors levels between female groups. Our results demonstrate that a reduction in pituitary sensitivity t o CRF, but not to AVP occur during lactation in the rat which mediates, at least in part, the stress hyporesponsiveness of lactation.