The HSD17B1 Knockout KGN Cell Line is a precisely engineered, CRISPR/Cas9-edited knockout cell line designed to eliminate functional expression of the HSD17B1 gene. This loss-of-function model enables systematic investigation of 17??-hydroxysteroid dehydrogenase type 1 activity and its role in estrogen metabolism within a human ovarian granulosa cell context. By disrupting the gene encoding the enzyme responsible for the reductive conversion of estrone (E1) to estradiol (E2), researchers can dissect local estrogen biosynthesis, steroid hormone amplification, and downstream signaling events critical to reproductive physiology and hormone-dependent pathologies.
The parental KGN cell line is an immortalized human ovarian granulosa cell model originally derived from an invasive granulosa cell carcinoma. These cells retain hallmark characteristics of steroidogenic granulosa cells, including responsiveness to gonadotropins, expression of key steroidogenic enzymes, and the capacity for robust estrogen synthesis. KGN cells are widely used to study ovarian follicle development, steroidogenesis, and the molecular mechanisms underlying ovarian cancer. The granulosa cell origin makes this line particularly relevant for investigating paracrine and autocrine estrogen signaling in the ovarian microenvironment.
HSD17B1 encodes a member of the short-chain dehydrogenase/reductase family that catalyzes the NADPH-dependent reduction of the weak estrogen estrone (E1) into the highly active estradiol (E2), as well as the conversion of androstenedione to testosterone. This enzyme is a critical regulator of local estrogen availability. Its expression is modulated by upstream regulators including FSH, LH, cAMP/PKA signaling, and transcription factors GATA and SF-1 (NR5A1). Estradiol produced activates estrogen receptors (ER??/ER??), inducing target genes such as GREB1, TFF1, and PR. HSD17B1 interacts with steroidogenic enzymes like aromatase (CYP19A1) and 3??-HSD, forming a network that controls androgen-estrogen balance.
In steroidogenic granulosa cells, HSD17B1 plays a pivotal role in potentiating estrogen receptor-mediated transcriptional programs that drive cell proliferation, differentiation, and survival. Disruption of HSD17B1 in the KGN background abrogates the conversion of estrone to estradiol, thereby impairing estrogen-dependent signaling and providing a clean loss-of-function model to dissect the contribution of intracrine estrogen synthesis to granulosa cell biology. This knockout cell line is invaluable for dissecting the estrogenic control of follicle development and for modeling pathologies where aberrant HSD17B1 activity is implicated, such as endometriosis, polycystic ovary syndrome, and hormone-responsive cancers.
This HSD17B1 knockout cell line supports a wide array of research applications, including studies on estrogen biosynthesis regulation, endocrine therapy resistance, and ovarian cancer pathogenesis. Typical assays performed with this model include estradiol ELISA to quantify hormone output, quantitative real-time PCR and western blotting to confirm HSD17B1 ablation, aromatase activity measurements, and estrogen receptor-dependent luciferase reporter assays. The cells are also suitable for functional assays such as migration, invasion, and drug sensitivity screening to evaluate the role of HSD17B1 in tumor progression and therapeutic response. For inquiries or to discuss custom services, please contact Ascent Research.
