PMID- 9433928
OWN - NLM
STAT- MEDLINE
DCOM- 19980204
LR  - 20190512
IS  - 1360-9947 (Print)
IS  - 1360-9947 (Linking)
VI  - 3
IP  - 11
DP  - 1997 Nov
TI  - Differential expression of matrix metalloproteinases and their tissue inhibitors 
      in leiomyomata: a mechanism for gonadotrophin releasing hormone agonist-induced 
      tumour regression.
PG  - 1005-14
AB  - Tissue remodelling involving extracellular matrix (ECM) turnover plays a major 
      role in leiomyoma growth and regression, regulated by the combined action of 
      matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs). We 
      postulated that leiomyomata express MMP and TIMP mRNA and protein, and their 
      expression is inversely regulated during tumour growth and gonadotrophin 
      releasing hormone agonist (GnRHa)-induced regression. We therefore examined the 
      expression of mRNA and protein for MMPs (interstitial collagenase, MMP-1; 
      gelatinases, MMP-2 and MMP-9; and stromelysin, MMP-3) and TIMPs (TIMP-1 and 
      TIMP-2) in leiomyoma and matched unaffected myometrium from GnRHa 
      (lupron)-treated and untreated patients. Reverse transcription-polymerase chain 
      reaction (RT-PCR) and restriction enzyme analysis revealed that leiomyomata and 
      myometrium expressed MMP-1, -2, -3 and -9, as well as TIMP-1 and -2 mRNA. 
      Quantitative RT-PCR indicated that leiomyomata and myometrium during the 
      secretory phase of the menstrual cycle expressed higher levels of MMP and TIMP 
      mRNA compared to the proliferative phase (P < 0.05), with low to undetectable 
      levels of MMP-1, -2 and -3 mRNA in the tumours. GnRHa therapy induced an overall 
      reduction in MMP and TIMP mRNA expression in both leiomyomata and myometrium, but 
      a significant decrease in TIMP-1, and an increase in MMP mRNA expression compared 
      with untreated tumours (P < 0.05). Immunohistochemically, MMP-1, -2, -3 and -9 
      and TIMP-1 and -2 proteins were localized in leiomyomata and myometrial smooth 
      muscle cells, arteriole wall and connective tissue fibroblasts, with an overall 
      increase in MMP and a decrease in TIMP staining intensity in GnRHa-treated 
      groups. The results suggest that MMP and TIMP expression in leiomyoma and 
      myometrium are hormonally regulated, and that GnRHa-induced tumour regression is 
      accompanied by an increase in MMP expression with a concomitant decrease in 
      TIMP-1 expression, which may potentially provide an environment favouring ECM 
      degradation.
FAU - Dou, Q
AU  - Dou Q
AD  - Department of Obstetrics and Gynecology, University of Florida, College of 
      Medicine, Gainesville 32610, USA.
FAU - Tarnuzzer, R W
AU  - Tarnuzzer RW
FAU - Williams, R S
AU  - Williams RS
FAU - Schultz, G S
AU  - Schultz GS
FAU - Chegini, N
AU  - Chegini N
LA  - eng
PT  - Journal Article
PL  - England
TA  - Mol Hum Reprod
JT  - Molecular human reproduction
JID - 9513710
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Adult
MH  - Cell Division/drug effects
MH  - Female
MH  - Gonadotropin-Releasing Hormone/agonists/*metabolism/pharmacology
MH  - Humans
MH  - Immunohistochemistry
MH  - Leiomyoma/*metabolism/pathology
MH  - Metalloendopeptidases/*biosynthesis
MH  - Middle Aged
MH  - RNA, Messenger/analysis
MH  - Tissue Inhibitor of Metalloproteinase-1/*biosynthesis
MH  - Tissue Inhibitor of Metalloproteinase-2/*biosynthesis
MH  - Uterine Neoplasms/*metabolism/pathology
EDAT- 1998/01/20 00:00
MHDA- 1998/01/20 00:01
CRDT- 1998/01/20 00:00
PHST- 1998/01/20 00:00 [pubmed]
PHST- 1998/01/20 00:01 [medline]
PHST- 1998/01/20 00:00 [entrez]
AID - 10.1093/molehr/3.11.1005 [doi]
PST - ppublish
SO  - Mol Hum Reprod. 1997 Nov;3(11):1005-14. doi: 10.1093/molehr/3.11.1005.