Work

scRNA-seq of the pituitary from the letrozole-induced polycystic ovary syndrome mouse model revealed abnormal prolactin signaling between immune cells and endocrine cells 3931

Year: 2025

Type: article

Abstract: Description Polycystic ovary syndrome (PCOS) is the most common multisystem disorder among premenopausal women. A classic PCOS phenotype is the hypersecretion of the luteinizing hormone (LH) from the vascularized pituitary gland, but increasing evidence suggests another pituitary hormone, prolactin (PRL), with associated metabolic risks in PCOS. Cellular dysregulations localized in the pituitary have not been thoroughly investigated for PCOS, specifically, alterations to the immune microenvironment. We analyzed the single-cell mRNA sequence of pituitaries from the letrozole-induced (LET) PCOS mouse model to investigate changes to the cellar composition and dysregulated pathways. Like the serum hormone levels, Prl-expressing endocrine cells decreased and Lh-expressing endocrine cells increased in LET mice compared to placebo-treated mice. Both endocrine and immune populations experienced a significant down-regulation of Prl, while all hormone-producing cells expressed the receptor gene, Prlr. Macrophages were the most abundant immune cell type, and unexpectedly, one subtype highly expressed Prl. These findings suggested a dysregulation in PRL signaling, and a PRL treatment on the LβT2 mouse pituitary cell line resulted in dosage-dependent changes in LH secretion. The transcriptome of the PCOS pituitary emphasized the hormonal regulation of PRL from both endocrine and immune cells, and further research on its role in the pathophysiology may expand therapeutic options to immunomodulation. Funding Sources Supported by NIH NICHD R00 HD098330; NIH NIAID DP2AI1121; NIH NIDDK DP1 DK130640. Topic Categories Cytokines and Chemokines and Their Receptors (CCR)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1673

Authors: Gabriela De Robles, Zena Marie Del Mundo, Christopher Garcia, Naveena Ujagar, Marcus Seldin, Dequina Nicholas

Institution: University of California, Irvine

Language: English

Topic: Ovarian function and disorders

Subfield: Reproductive Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases