Hormone Regulation of Corticotropin-Releasing Factor Receptor 1 in the Female Mouse Brain

Introduction: Corticotropin-releasing factor receptor 1 (CRFR1) is a key regulator of neuroendocrine and behavioral stress responses. Previous studies have demonstrated that CRFR1 in certain hypothalamic and preoptic brain areas is modified by chronic stress and during the postpartum period in female mice, although the potential hormonal contributors to these changes are unknown. Methods: This study focused on determining the contributions of hormones associated with stress and the maternal period (glucocorticoids, prolactin, estradiol/progesterone) on CRFR1 levels using a CRFR1-GFP reporter mouse line and immunohistochemistry. Results: Administration of dexamethasone, an agonist of the glucocorticoid receptor, elevated CRFR1 in the anteroventral periventricular nucleus (AVPV/PeN) and paraventricular hypothalamus (PVN) with no changes found in the medial preoptic area (MPOA) or arcuate nucleus. Treatment with prolactin for 5 days elevated CRFR1 levels in the MPOA with no changes in other regions. Finally, we utilized the hormone-simulated pseudopregnancy (HSP) paradigm to mimic changes in estradiol and progesterone across pregnancy and the early postpartum period. Female mice receiving HSP treatment, as well as mice receiving HSP treatment that then underwent 5 days of estrogen withdrawal (EW), showed alterations in CRFR1 relative to control groups that mirrored changes previously reported in postpartum mice. Specifically, CRFR1 levels increased in the AVPV/PeN and decreased in the MPOA and PVN, with no changes found in the arcuate nucleus. HSP- and EW-treated mice also showed decreases in tyrosine hydroxylase-expressing neurons in the AVPV/PeN. Discussion/Conclusion: Overall, these hormone-induced changes in stress-regulating CRFR1 neurons may impact behavioral and neuroendocrine stress responses.