Regulation of matrix metalloproteinase-19 messenger RNA expression in the rat ovary

Misung Jo1, Thomas E Curry

  • 1Department of Obstetrics and Gynecology, Chandler Medical Center, University of Kentucky, Lexington, Kentucky 40536-0298, USA. mjo2@uky.edu

Insights

Matrix metalloproteinase-19 (MMP-19) mRNA expression increases during ovarian follicular growth, ovulation, and luteal regression. Its induction is regulated by luteinizing hormone (LH) and protein kinase pathways, requiring new protein synthesis.

Area of Science:

  • Reproductive biology
  • Molecular endocrinology
  • Ovarian physiology

Background:

  • Matrix metalloproteinases (MMPs) are crucial for ovarian tissue remodeling.
  • MMP-19 mRNA induction is noted in periovulatory follicles in mice.
  • Limited information exists on MMP-19 expression across the ovarian cycle and its regulation.

Purpose of the Study:

  • To investigate MMP-19 mRNA expression patterns throughout the rat ovarian cycle.
  • To elucidate the periovulatory regulation of MMP-19 mRNA expression in the rat ovary.

Main Methods:

  • Analysis of MMP-19 mRNA expression in rat ovaries during follicular and luteal phases.
  • Localization studies of MMP-19 mRNA in ovarian follicles.
  • In vivo and in vitro studies using gonadotropin stimulation and follicular cell cultures to investigate regulatory pathways.
  • Treatment with LH, protein kinase activators, cycloheximide, progesterone receptor antagonists, and prostaglandin synthesis inhibitors.

Main Results:

  • MMP-19 mRNA levels increased during follicular growth and ovulation in immature rat ovaries.
  • MMP-19 mRNA was localized to theca-interstitial and granulosa cells of developing and periovulatory follicles.
  • Similar expression patterns were observed in naturally cycling adult rats, with accumulation in regressing corpora lutea.
  • LH, PKA, and PKC pathways, but not progesterone or prostaglandin signaling, mediated hCG-induced MMP-19 mRNA expression in granulosa cells.
  • LH- or forskolin-induced MMP-19 mRNA expression required de novo protein synthesis.

Conclusions:

  • MMP-19 mRNA is dynamically expressed during key ovarian events including follicular growth, ovulation, and luteal regression.
  • The periovulatory induction of MMP-19 mRNA is regulated by LH and protein kinase pathways, dependent on new protein synthesis.
  • These findings suggest a significant role for MMP-19 in ovarian remodeling processes.

Related Concept Videos

Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...