title: Altered pituitary sensitivity to corticotropin-releasing factor and arginine vasopressin participates in the stress hyporesponsiveness of lactation in the rat.
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.
authors.affiliation: McGill University, Department of Psychiatry and Department of Neurology and Neurosurgery, Douglas Hospital Research Centre, Montreal, Canada.
authors.forename: D J
authors.initials: DJ
authors.lastname: Toufexis
authors.forename: S
authors.initials: S
authors.lastname: Tesolin
authors.forename: N
authors.initials: N
authors.lastname: Huang
authors.forename: C
authors.initials: C
authors.lastname: Walker
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001345:Autoradiography; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004359:Drug Therapy, Combination; D005260:Female; D007774:Lactation / Q000097:blood / Q000502:physiology*; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D017483:Receptors, Vasopressin / Q000378:metabolism; D013312:Stress, Physiological / Q000097:blood / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D018019:Receptors, Corticotropin-Releasing Hormone; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone