PARENT SESSION

(W567) CENTRAL ADMINISTRATION OF THE PROLACTIN RECEPTOR ANTAGONIST, S-179D PRL, DISRUPTS PARTURITION IN RATS: POSSIBLE ENDOCRINE INVOLVEMENT.

Nephew, Benjamin¹, Amico, Janet², Cai, H. M.², Walker, Ameae³, Scanlan, Victoria¹, Bridges, Robert¹, ¹ Tufts University School of Veterinary Medicine, N. Grafton, MA² University of Pittsburgh School of Medicine, Pittsburgh, PA³ University of California Riverside, Riverside, CA

ABSTRACT- The prolactin (PRL) receptor antagonist S-179D PRL delays the onset of maternal behavior in steroid-primed nulliparous female rats (Endocrinology 142:730, 2001). In the present study, S-179D PRL was centrally administered to pregnant rats on gestation day 21 to investigate the role of endogenous prepartum PRL in maternal behavior at the time of parturition. The S-179D PRL treatments (0.01 to 1.0 ng/hr administered by ALZET minipump to the lateral ventricle) resulted in a severe disruption of parturition. To determine the cause of this disruption, a second group of catheterized animals was administered S-179D (0.001, 0.1 ng/hour,) or vehicle control, and serial blood samples were taken at 0900, 1300, 1700, and 2100 on gestation days 21-23. Samples were assayed for PRL, progesterone, and oxytocin. Significantly more S-179D PRL-treated rats failed to deliver by 1500 on day 23 of gestation (85.7% of the 0.1ng/hr animals, 100% of the 0.001 ng/hr animals, versus 33% of controls). No significant effects of S-179D on plasma progesterone or oxytocin were detected, although the afternoon decline in oxytocin levels on day 21 appeared blunted in S-179D PRL-treated rats. The higher dose of S179D PRL significantly suppressed the prepartum rise in PRL, while the lower dose failed to affect plasma PRL levels. Thus, while it appears that the disruption of parturition by S-179D PRL does not depend on significant alterations in progesterone or PRL secretion, the disruption may be associated with a shift in the prepartum pattern of oxytocin activity. Supported by PHS grant HD19789 awarded to RSB.

KEY WORDS: prolactin, parturition, oxytocin, progesterone