VCAM1 Is Induced in Ovarian Theca and Stromal Cells in a Mouse Model of Androgen Excess
Year: 2019
Type: article
Abstract: Ovarian theca androgen production is regulated by the pituitary LH and intrafollicular factors. Enhanced androgen biosynthesis by theca cells contributes to polycystic ovary syndrome (PCOS) in women, but the ovarian consequences of elevated androgens are not completely understood. Our study documents the molecular events that are altered in the theca and stromal cells of mice exposed to high androgen levels, using the nonaromatizable androgen DHT. Changes in ovarian morphology and function were observed not only in follicles, but also in the stromal compartment. Genome-wide microarray analyses revealed marked changes in the ovarian transcriptome of DHT-treated females within 1 week. Particularly striking was the increased expression of vascular cell adhesion molecule 1 (Vcam1) specifically in the NR2F2/COUPTF-II lineage theca cells, not granulosa cells, of growing follicles and throughout the stroma of the androgen-treated mice. This response was mediated by androgen receptors (ARs) present in theca and stromal cells. Human theca-derived cultures expressed both ARs and NR2F2 that were nuclear. VCAM1 mRNA and protein were higher in PCOS-derived theca cells compared with control theca and reduced markedly by the AR antagonist flutamide. In the DHT-treated mice, VCAM1 was transiently induced by equine chorionic gonadotropin, when androgen and estrogen biosynthesis peak in preovulatory follicles, and was potently suppressed by a superovulatory dose of human chorionic gonadotropin. High levels of VCAM1 in the theca and interstitial cells of DHT-treated mice and in adult Leydig cells indicate that there may be novel functions for VCAM1 in reproductive tissues, including the gonads.
Source: Endocrinology
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Cancer Prevention and Research Institute of Texas, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, NIH Office of the Director, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Steroid Hormones Regulate Ovarian Cancer Progression and Metastasis, G1798973223, Mechanisms Controlling Divergent Fates of Ovarian Follicles and Fertility, Baylor Intellectual and Developmental Disabilities Research Centers, Initiative for Maximizing Student Development (IMSD) Program, G4322161087, Novel Aspect of Androgen Action in Ovarian Cell Function and Dysfunction, G4636744469, The Combinatorial Drug Discovery Program (CDDP), Program in Human and Molecular Genetics, G7004368190, Insulin and Androgen Interactions in the Infertility of Obesity, Functional Analysis of PCOS Candidate Genes, G7951094840, YEARS 19 - 23: BCM POST-BACCALAUREATE RESEARCH EDUCATION PROGRAM, Tecan EVO GenePaint robot, CRR LIGAND ASSAY AND ANALYSIS CORE, Texas Medical Center Digestive Diseases Center, Baylor College of Medicine Cancer Center - Cancer Center Support Grant
OpenAlex ID: W2929008901