Document Detail

Absence of Central Circadian Pacemaker Abnormalities in Humans With Loss of Function Mutation in Prokineticin 2.
MedLine Citation:
PMID:  24423319     Owner:  NLM     Status:  Publisher    
Context: Loss of prokineticin 2 (PROK2) signaling in mice disrupts circadian rhythms, but the role of PROK2 signaling in the regulation of circadian rhythms in humans is undetermined. Objective: The aim of the study was to examine the circadian rhythms of humans with complete loss-of-function PROK2 mutation using an inpatient constant routine (CR) protocol. Design and Setting: We conducted a case study in an academic medical center. Subjects and Methods: Two siblings (one male and one female, ages 67 and 62 y, respectively) with isolated GnRH deficiency (IGD) due to a biallelic loss-of-function PROK2 mutation were studied using an inpatient CR protocol. Historical data from inpatient CR protocols conducted in healthy controls (ages 65-81 y) were used for comparison. Main Outcome Measures: We measured circadian phase markers (melatonin, cortisol, and core body temperature) and neurobehavioral performance (psychomotor vigilance task [PVT] and subjective alertness scale). Results: Circadian waveforms of melatonin and cortisol did not differ between the IGD participants with PROK2 mutation and controls. In both IGD participants, neurobehavioral testing with PVT showed disproportionate worsening of PVT lapses and median reaction time in the second half of the CR. Conclusions: Humans with loss of PROK2 signaling lack abnormalities in circadian phase markers, indicating intact central circadian pacemaker activity in these patients. These results suggest that PROK2 signaling in humans is not required for central circadian pacemaker function. However, impaired PVT in the PROK2-null participants despite preserved endocrine rhythms suggests that PROK2 may transmit circadian timing information to some neurobehavioral neural networks.
Ravikumar Balasubramanian; Daniel A Cohen; Elizabeth B Klerman; Duarte Pignatelli; Janet E Hall; Andrew A Dwyer; Charles A Czeisler; Nelly Pitteloud; William F Crowley
Related Documents :
23367329 - Use of galvanic vestibular feedback for a balance prosthesis.
23893829 - High-versus low-frequency stimulation effects on fine motor control in chronic hemipleg...
18678759 - The effects of a newly designed twin-slot bracket on severely malpositioned teeth--a ty...
23039449 - Restoration of loudness summation and differential loudness growth in hearing-impaired ...
24206979 - Tactile sensibility on the fingernail.
3901379 - Occlusal forces and chewing ability in dentitions with cross-arch bridges.
24535839 - The adaptive value of primate color vision for predator detection.
11979169 - Intraoperative measurement of lumbar spine motion segment stiffness.
8550939 - Age effects on duration discrimination with simple and complex stimuli.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-1
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  -     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-1-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  jc20132096     Citation Subset:  -    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Associations of Serum Sclerostin and Polymorphisms in the SOST Gene with Bone Mineral Density and Ma...
Next Document:  The VEGF inhibitor axitinib has limited effectiveness as a therapy for adrenocortical cancer.