Category: Pituitary Disorders/Neuroendocrinology
FK506 binding protein 51 (FKBP5) is a co-chaperone regulator of the glucocorticoid receptor GR (GR). By partnering with heat shock protein 90, FKBP5 blocks the interaction of the GR complex with the transport protein dynein, resulting in delayed GR nuclear translocation. Recent studies have demonstrated that measurement of FKBP5 mRNA expression in circulating blood can serve as a biomarker for glucocorticoid action and this has been extensively studies in psychiatric disorders. More recently, a study reported increased FKBP5 mRNA in patients with Cushing disease (CD) which returned to levels seen in healthy controls following successful trans-nasal trans-sphenoidal (TNTS) surgical tumor removal. However, the expression of circulating FKBP5 mRNA levels in other pituitary tumor subtypes is unknown.
Pre-operative blood was collected from undergoing TNTS for pituitary tumors (n=22) at between 2015-2018. Post-operative blood was also collected in 3 CD patients. Total RNA was isolated from blood using RiboPure blood RNA isolation kit and reverse transcribed for real-time qPCR analysis using Taqman Universal Master Mix II with UNG. Relative FKBP5 expression was determined using the 2-ΔΔCT normalized by GAPDH.
Highest FKBP5 mRNA levels were measured in 5 patients with CD (Mean±SD, 0.453± 0.016) in comparison to 10 patients with clinically non-functional tumors (Mean±SD, 0.335±0.051), 2 with prolactinomas (Mean±SD, 0.311±0.053), 2 with acromegaly (Mean±SD, 0.237±0.048), 1 with a Crooke’s cell adenoma (Mean±SD, 0.119±0.017) and 2 with a null cell adenoma (Mean±SD, 0.212± 0.024). In 3 patients with CDs in remission in whom follow-up samples were collected, FKBP5 mRNA levels fell (Mean±SD, 0.118±0.005) and were similar to those measured in healthy controls (Mean±SD, 0.112±0.01).
This pilot study demonstrates that circulating FKBP5 mRNA expression is elevated in patients with CD compared to other pituitary tumor subtypes (p<0.05, unpaired t test), and falls to levels similar to healthy controls after successful surgical tumor removal (p<0.05). However the specificity of circulating FKBP5 measurement is unclear as we noted one patient with a CNFT and a history of severe anxiety that exhibited high circulating FKBP5 mRNA expression (Mean±SD, 1.49±0.13).
Conclusion : Further studies of the role of circulating FKBP5mRNA as a biomarker of glucocorticoid action are needed to determine its utility in distinguishing patients with CD from other pituitary tumor subtypes and other overlap disorders including psychiatric disorders.
Dongyun Zhang– Assistant Project Scientist, UCLA, Los Angeles, California
Argishty Mirzakhanian– Volunteer, UCLA
Yingying Yang– Visiting graduate researcher, UCLA
Marvin Bergsneider– Professor, UCLA
Marilene B. Wang– Professor, UCLA
William H. Yong– Professor, UCLA
Anthony Heaney– Professor, UCLA
Assistant Project Scientist
Los Angeles, California
Dr. Zhang has been working at UCLA-David Geffen School of Medicine, Department of Medicine for 5 years focusing on pituitary tumor basic and translational research
Mr. Argishty Mirzakhanian is a volunteer working in Dr. Heaney laboratory and his contribution to this abstract mainly was analysis of pituitary tumor patient peripheral blood
Visiting graduate researcher
Dr. Yingying Yang is a visiting graduate research in Dr. Heaney laboratory at UCLA and she participated in the statistical analysis
Dr. Marvin Bergsneider is the lead neurosurgeon at UCLA and he performs 100-200 pituitary tumor surgeries annually
Dr. Marilene B. Wang is the lead Head & Neck surgeon at UCLA and she together with Dr. Marvin Bergsneider perform 100-200 pituitary tumors surgeries annually
Dr. William H. Yong is the neuropathologist who's in charge of surgical resected pituitary tumor pathological diagnosis.
Anthony P. Heaney, MD, PhD is an Associate Professor at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA). His primary areas of clinical and research interest involve the pathogenesis of pituitary tumors and exploiting novel molecular targets to develop innovative treatments for pituitary tumors, and other neuroendocrine tumors.