PMID- 25910436
OWN - NLM
STAT- MEDLINE
DCOM- 20151103
LR  - 20181202
IS  - 1095-6840 (Electronic)
IS  - 0016-6480 (Print)
IS  - 0016-6480 (Linking)
VI  - 216
DP  - 2015 May 15
TI  - Matrix metalloproteinase inhibition influences aspects of photoperiod stimulated 
      ovarian recrudescence in Siberian hamsters.
PG  - 46-53
LID - S0016-6480(15)00110-0 [pii]
LID - 10.1016/j.ygcen.2015.04.010 [doi]
AB  - Blocking matrix metalloproteinase (MMP) activity in vivo with inhibitor GM6001 
      impedes photostimulated ovarian recrudescence in photoregressed Siberian 
      hamsters. Since direct and indirect effects of MMPs influence a myriad of ovarian 
      functions, we investigated the effect of in vivo MMP inhibition during 
      recrudescence on ovarian mRNA expression of steroidogenic acute regulatory 
      protein (StAR), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), Cyp19a1 aromatase, 
      epidermal growth factor receptor (EGFR), amphiregulin (Areg), estrogen receptors 
      (Esr1 and Esr2), tissue inhibitors of MMPs (TIMP-1,-2,-3), proliferating cell 
      nuclear antigen (PCNA), vascular endothelial growth factor A (VEGFA), its 
      receptor VEGFR-2, and angiopoietin-2 (Ang-2). Female Siberian hamsters were 
      randomly assigned to one of four photoperiod groups: stimulatory long (LD) or 
      inhibitory short (SD) photoperiods, or transferred from SD to LD for 2 weeks 
      (post-transfer, PT). Half of the PT hamsters were injected (ip) daily with GM6001 
      (PTG). SD exposure reduced ovarian StAR, 3beta-HSD, Cyp19a1, Esr1, Esr2, TIMPs 2-3, 
      PCNA, VEGFR-2 and Ang-2 mRNA expression (p<0.05), and 2 weeks of photostimulation 
      restored mRNA expression of 3beta-HSD and PCNA and increased Areg and VEGFA mRNA 
      expression in the PT group. GM6001 treatment during photostimulation (PTG) 
      increased TIMP-1, -2 and -3 and PCNA mRNA, but inhibited Areg mRNA expression 
      compared to PT. Neither photoperiod nor GM6001 altered EGFR expression. Results 
      of this study suggest that in vivo inhibition of MMP activity by GM6001 may 
      impede ovarian recrudescence, particularly follicular growth, in two ways: (1) 
      directly by partially inhibiting the release of EGFR ligands like Areg, thereby 
      potentially affecting EGFR activation and its downstream pathway, and (2) 
      indirectly by its effect on TIMPs which themselves can affect proliferation, 
      angiogenesis and follicular growth.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Shahed, Asha
AU  - Shahed A
AD  - Reproductive Biology Group, Department of Biological Sciences, California State 
      University Long Beach, Long Beach, CA 90840, United States.
FAU - Simmons, Jamie J
AU  - Simmons JJ
AD  - Reproductive Biology Group, Department of Biological Sciences, California State 
      University Long Beach, Long Beach, CA 90840, United States.
FAU - Featherstone, Sydney L
AU  - Featherstone SL
AD  - Reproductive Biology Group, Department of Biological Sciences, California State 
      University Long Beach, Long Beach, CA 90840, United States.
FAU - Young, Kelly A
AU  - Young KA
AD  - Reproductive Biology Group, Department of Biological Sciences, California State 
      University Long Beach, Long Beach, CA 90840, United States. Electronic address: 
      kelly.young@csulb.edu.
LA  - eng
GR  - SC3 GM089611/GM/NIGMS NIH HHS/United States
GR  - SC3GM089611/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150421
PL  - United States
TA  - Gen Comp Endocrinol
JT  - General and comparative endocrinology
JID - 0370735
RN  - 0 (Biomarkers)
RN  - 0 (Dipeptides)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan 
      methylamide)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (steroidogenic acute regulatory protein)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - EC 1.1.- (17-Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.51 (3 (or 17)-beta-hydroxysteroid dehydrogenase)
RN  - EC 1.14.14.1 (Aromatase)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - 17-Hydroxysteroid Dehydrogenases/genetics/metabolism
MH  - Animals
MH  - Aromatase/genetics/metabolism
MH  - Biomarkers/*metabolism
MH  - Cricetinae
MH  - Dipeptides/*pharmacology
MH  - ErbB Receptors/genetics/metabolism
MH  - Female
MH  - Matrix Metalloproteinase Inhibitors/*pharmacology
MH  - Matrix Metalloproteinases/*chemistry/genetics/metabolism
MH  - Ovary/drug effects/*physiology/radiation effects
MH  - Phosphoproteins/genetics/metabolism
MH  - *Photoperiod
MH  - Proliferating Cell Nuclear Antigen/genetics/metabolism
MH  - RNA, Messenger/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Estrogen/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tissue Inhibitor of Metalloproteinase-2/genetics/metabolism
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
PMC - PMC4457603
MID - NIHMS683410
OTO - NOTNLM
OT  - EGFR
OT  - MMP
OT  - Photoperiod
OT  - Recrudescence
OT  - TIMPs
EDAT- 2015/04/26 06:00
MHDA- 2015/11/04 06:00
PMCR- 2016/05/15
CRDT- 2015/04/26 06:00
PHST- 2014/10/29 00:00 [received]
PHST- 2015/03/04 00:00 [revised]
PHST- 2015/04/12 00:00 [accepted]
PHST- 2015/04/26 06:00 [entrez]
PHST- 2015/04/26 06:00 [pubmed]
PHST- 2015/11/04 06:00 [medline]
PHST- 2016/05/15 00:00 [pmc-release]
AID - S0016-6480(15)00110-0 [pii]
AID - 10.1016/j.ygcen.2015.04.010 [doi]
PST - ppublish
SO  - Gen Comp Endocrinol. 2015 May 15;216:46-53. doi: 10.1016/j.ygcen.2015.04.010. 
      Epub 2015 Apr 21.