SAT-034 Regulation of Pituitary NR4A Orphan Receptors and Their Role in Prolactin Secretion

Abstract Disclosure: R. Terashima: None. S. Kurusu: None. M. Kawaminami: None. The nuclear orphan receptors NR4A1, NR4A2, and NR4A3 (NR4As) are immediate early genes induced by stress factors and involved in diverse cellular processes via transcriptional regulation. While NR4As are expressed in pituitary endocrine cells, including lactotrophs, their specific role in prolactin (PRL) regulation remains unclear. This study investigates the relationship between pituitary NR4A expression and physiological PRL secretion in pseudopregnant, pregnant, and lactating rats. In pseudopregnant rats, pituitary NR4A expression increased concurrently with the diurnal PRL surge and declined following the nocturnal surge. A comparable nighttime elevation in NR4A expression was observed during early pregnancy but was absent in mid-to-late pregnancy. In lactating rats, NR4A expression mirrored PRL secretion patterns, decreasing upon weaning. Dopamine agonist (DA) administration significantly suppressed both PRL secretion and NR4A expression in pseudopregnant and lactating rats. In primary pituitary cell cultures, DA dose-dependently reduced PRL secretion and NR4A expression. Furthermore, siRNA-mediated knockdown of NR4A2 significantly decreased PRL levels in the culture medium without affecting Prl gene expression. These findings suggest that dopamine suppresses NR4A expression in lactotrophs, and while at least NR4A2 do not directly regulate Prl transcription, it may modulate PRL secretion through alternative mechanisms. Presentation: Saturday, July 12, 2025