title: Sleep deprivation enhances peripheral serotonin secretion to regulate the large follicle steroidogenesis of rats.
abstract: OBJECTIVE
  Sleep deprivation (SD) leads to the disturbance of the estrous cycle. Serotonin, the levels of which increase with SD, has been shown to inhibit luteinizing hormone production and the receptor has been found in the follicles. In this study, the serotonin effect on preovulatory follicular steroidogenesis is investigated and the underlying mechanisms are elucidated.
  
  
  METHODS
  Female rats were subjected to SD for a time span of 1-4 days using the dish-over-water-method with a Rechtschaffen apparatus. Serum estradiol and serotonin concentrations were assessed; thereafter, they were evaluated with the effect of serotonin on the estradiol production and steroidogenic acute regulatory (StAR) protein expression in a serum-free culture system. Preovulatory follicles were dissected mechanically from the ovaries of 21-day-old rats, which induced follicle growth, and cultured for 24 hours with or without recombinant human follicle-stimulating hormone (FSH) in the presence or absence of serotonin.
  
  
  RESULTS
  SD, led to a significant decrease in serum estradiol concentrations, while serotonin concentrations were significantly elevated (all p < 0.05). Follicles were cultured with a constant dose of FSH (50 mIU/mL) and increasing doses of serotonin, estradiol production was reduced by 20%. The inhibitory effect of serotonin was concentration dependent. The addition of serotonin (0.1 μg/mL) decreased FSH-induced estradiol production and attenuated FSH-stimulated follicular StAR protein expression. The inhibitory effects of serotonin could be reduced by the serotonin receptor antagonist ketanserin.
  
  
  CONCLUSIONS
  These findings suggest that decreased serum estradiol concentrations in SD rats may be the result of serotonin-related inhibition of estradiol production and decreased large follicle expression of StAR protein.
authors.affiliation: Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan, ROC; Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan, ROC.
authors.forename: Chueh-Ko
authors.initials: CK
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, China Medical University and Hospital, Taichung, Taiwan, ROC.
authors.forename: Rick Sai-Chuen
authors.initials: RS
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan, ROC.
authors.forename: Cheng-Hsuan
authors.initials: CH
authors.lastname: Wu
authors.affiliation: School of Medicine, Royal College of Surgeons, Dublin, Ireland.
authors.forename: Theodore Rong-Yei
authors.initials: TR
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan, ROC. Electronic address: 64420@cch.org.tw.
authors.forename: Horng-Der
authors.initials: HD
authors.lastname: Tsai
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003345:Corticosterone / Q000097:blood; D004958:Estradiol / Q000096:biosynthesis / Q000097:blood*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000097:blood* / Q000378:metabolism / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D012892:Sleep Deprivation / Q000097:blood*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D012702:Serotonin Antagonists; D000098682:Steroidogenic Acute Regulatory Protein; D012701:Serotonin; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D007650:Ketanserin; D003345:Corticosterone
keywords: estradiol; preovulatory follicle; serotonin; sleep deprivation; steroidogenesis