De Guzman Rose M, Jacobskind Jason S, Rosinger Zachary J, Rybka Krystyna A, Parra Katherine E, Caballero Aya L, Sharif Massoud S, Justice Nicholas J, Zuloaga Damian G
Department of Psychology, University at Albany, State University New York, Albany, New York, USA.
Center for Metabolic and Degenerative Diseases, Brown Foundation Institute of Molecular Medicine of McGovern Medical School, University of Texas Health Sciences Center, Houston, Texas, USA.
Neuroendocrinology. 2024;114(12):1139-1157. doi: 10.1159/000542751. Epub 2024 Nov 25.
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.
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.
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.
促肾上腺皮质激素释放因子受体1（CRFR1）是神经内分泌和行为应激反应的关键调节因子。先前的研究表明，雌性小鼠下丘脑和视前区某些脑区的CRFR1在慢性应激和产后期间会发生改变，尽管尚不清楚导致这些变化的潜在激素因素。
本研究利用CRFR1-GFP报告基因小鼠品系和免疫组织化学方法，重点确定与应激和母期相关的激素（糖皮质激素、催乳素、雌二醇/孕酮）对CRFR1水平的影响。
给予糖皮质激素受体激动剂地塞米松后，室旁前腹侧核（AVPV/PeN）和下丘脑室旁核（PVN）中的CRFR1升高，而视前内侧区（MPOA）或弓状核未发现变化。催乳素处理5天可使MPOA中的CRFR1水平升高，其他区域无变化。最后，我们利用激素模拟假孕（HSP）范式来模拟整个孕期和产后早期雌二醇和孕酮的变化。接受HSP处理的雌性小鼠，以及接受HSP处理后再进行5天雌激素撤药（EW）的小鼠，与对照组相比，CRFR1发生了改变，这与先前产后小鼠报道的变化一致。具体而言，AVPV/PeN中的CRFR1水平升高，MPOA和PVN中的CRFR1水平降低，弓状核未发现变化。接受HSP和EW处理的小鼠在AVPV/PeN中表达酪氨酸羟化酶的神经元也减少。
讨论/结论：总体而言，这些激素诱导的应激调节CRFR1神经元变化可能会影响行为和神经内分泌应激反应。
