title: Inhibition of matrix metalloproteinases in Siberian hamsters impedes photostimulated recrudescence of ovaries.
abstract: Exposure of Siberian hamsters to short photoperiod for 14 weeks induces ovarian regression. Subsequent transfer to long photoperiod restores ovarian function, and 2 weeks of photostimulation increases plasma estradiol (E(2)), antral follicles, and corpora lutea (CL). Because tissue remodeling involved with photostimulated ovarian recrudescence is associated with differential expression of matrix metalloproteinases (MMPs), we hypothesized that inhibiting MMP activity using a broad-spectrum in vivo MMP inhibitor, GM6001, would curtail recrudescence. One group of hamsters was placed in long days (LD; 16 h light:8 h darkness) for 16 weeks. Another group was placed in inhibitory short days (SD; 8 h light:16 h darkness) for 14 weeks. A third group was placed in SD for 14 weeks and transferred to LD for 2 weeks to stimulate recrudescence. During weeks 14-16, animals were either not treated or treated daily with i.p. injections of GM6001 (20 mg/kg) or vehicle (DMSO). GM6001 reduced gelatinase activity and decreased immunohistochemical staining for MMP1, MMP2, and MMP3 compared with vehicle. No differences between controls, vehicle, or GM6001 treatment were observed among LD animals, despite a trend toward reduction in CL and E(2) with GM6001. Although SD reduced ovarian function, photostimulation of transferred controls increased uterine mass, plasma E(2), appearance of antral follicles, and CL. With GM6001 treatment, photostimulation failed to increase uterine mass, plasma E(2), antral follicles, or CL. These data show, for the first time, that in vivo GM6001 administration inhibits MMP activity in hamster ovaries during photostimulation, and indicate that this inhibition may impede photostimulated recrudescence of ovaries. This study suggests an intriguing link between MMP activity and return to ovarian function during photostimulated recrudescence.
authors.affiliation: Reproductive Biology Group, Department of Biological Sciences, California State University Long Beach, Long Beach, California 90840-3702, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Whited
authors.forename: Asha
authors.initials: A
authors.lastname: Shahed
authors.forename: Carling F
authors.initials: CF
authors.lastname: McMichael
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Young
mesh_terms: D000818:Animals; D002452:Cell Count; D006224:Cricetinae; D004151:Dipeptides / Q000494:pharmacology; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005260:Female; D008027:Light; D061965:Matrix Metalloproteinase Inhibitors; D009929:Organ Size / Q000187:drug effects / Q000528:radiation effects; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D010053:Ovary / Q000033:anatomy & histology / Q000187:drug effects* / Q000528:radiation effects; D010062:Ovulation Induction / Q000379:methods*; D017111:Phodopus; D010812:Physical Stimulation / Q000379:methods; D011480:Protease Inhibitors / Q000494:pharmacology*; D012008:Recurrence
chemical_list: D004151:Dipeptides; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors