title: Protective role of melatonin in progesterone production by human luteal cells.
abstract: This study investigated whether melatonin protects luteinized granulosa cells from reactive oxygen species (ROS) as an antioxidant to enhance progesterone production in the follicle during ovulation. Follicular fluid was sampled at the time of oocyte retrieval in women undergoing in vitro fertilization and embryo transfer (IVF-ET). Melatonin concentrations in the follicular fluid were positively correlated with progesterone concentrations (r = 0.342, P < 0.05) and negatively correlated with the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker (r = -0.342, P < 0.05). The progesterone and 8-OHdG concentrations were negatively correlated (r = -0.246, P < 0.05). Luteinized granulosa cells were obtained at the time of oocyte retrieval in women undergoing IVF-ET. Cells were incubated with H(2)O(2) (30, 50, 100 μm) in the presence or absence of melatonin (1, 10, 100 μg/mL). Progesterone production by luteinized granulosa cells was significantly inhibited by H(2)O(2). Melatonin treatment overcame the inhibitory effect of H(2) O(2) . Twenty-five patients who had luteal phase defect (serum progesterone concentrations <10 ng/mL during the mid-luteal phase) were divided into two groups during the next treatment cycle: 14 women were given melatonin (3 mg/day at 22:00 hr) throughout the luteal phase and 11 women were given no medication as a control. Melatonin treatment improved serum progesterone concentrations (>10 ng/mL during the mid-luteal phase) in nine of 14 women (64.3%), whereas only two of 11 women (18.1%) showed normal serum progesterone levels in the control group. In conclusion, melatonin protects granulosa cells undergoing luteinization from ROS in the follicle and contributes to luteinization for progesterone production during ovulation.
authors.affiliation: Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Taketani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamura
authors.forename: Akihisa
authors.initials: A
authors.lastname: Takasaki
authors.forename: Lifa
authors.initials: L
authors.lastname: Lee
authors.forename: Fumie
authors.initials: F
authors.lastname: Kizuka
authors.forename: Isao
authors.initials: I
authors.lastname: Tamura
authors.forename: Ken
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Ryo
authors.initials: R
authors.lastname: Maekawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Asada
authors.forename: Katsunori
authors.initials: K
authors.lastname: Shimamura
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sugino
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D002478:Cells, Cultured; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008184:Luteal Cells / Q000166:cytology / Q000378:metabolism*; D008183:Luteal Phase / Q000097:blood*; D008550:Melatonin / Q000008:administration & dosage*; D016877:Oxidants / Q000494:pharmacology; D011374:Progesterone / Q000097:blood*
chemical_list: D000975:Antioxidants; D016877:Oxidants; D011374:Progesterone; D006861:Hydrogen Peroxide; D008550:Melatonin