Messenger ribonucleic acids for MAC25 and connective tissue growth factor (CTGF) are inversely regulated during folliculogenesis and early luteogenesis

Endocrinology. 2000 Jul;141(7):2648-57. doi: 10.1210/endo.141.7.7576.


Cell proliferation, terminal differentiation, and angiogenesis occur during cycles of follicular and luteal development. In other paradigms, mac25, a potent tumor inhibitor is strongly induced in senescent epithelial cells, whereas CTGF stimulates angiogenesis and wound healing. Using in situ hybridization and immunohistochemistry, we have examined the possibilities that mac25 is inhibited, whereas CTGF is induced during active periods of follicular development and luteogenesis. Ovaries were collected during the follicular and early luteal phases from prostaglandin F2alpha-treated mature pigs and from slaughterhouse sows. CTGF transcripts were induced during the late preantral stage in granulosa and theca cells concomitantly with the appearance of endothelial cells in the theca. CTGF mRNA expression increased in granulosa cells to a maximum (P < 0.01) in mid-antral follicles but was down regulated (P < 0.01) in preovulatory follicles. In contrast, granulosa cell mac25 mRNA expression was undetectable between the preantral and mid-antral stage but was strongly induced in terminally differentiated granulosa cells of preovulatory follicles. CTGF mRNA and peptide were also detected in the theca externa/interstitium and in vascular endothelial cells of ovarian blood vessels, whereas mac25 transcripts, which were also abundant in ovarian blood vessels increased in the theca interna with follicular development. Transcripts of cyclin D 1, a marker of cell proliferation, appeared during the early antral stage and were moderate in granulosa cells but abundant in capillary endothelial cells in the theca interna, underneath the basement membrane. Following ovulation, CTGF and cyclin D1 mRNAs were associated with the migration of endothelial cells into the CL. Subsequently, there was a marked up-regulation of CTGF mRNA expression in granulosa luteins concomitantly with an increase in endothelial cell proliferation within the CL. We hypothesize that CTGF may promote ovarian cell growth and blood vessel formation during follicular and luteal development whereas mac25, a tumor inhibitor, may promote terminal differentiation of granulosa cells in preovulatory follicles.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biomarkers
  • Blood Vessels / metabolism
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Connective Tissue Growth Factor
  • Corpus Luteum / cytology
  • Corpus Luteum / metabolism
  • Corpus Luteum / physiology*
  • Cyclin D1 / genetics
  • Female
  • Growth Substances / genetics*
  • Growth Substances / metabolism
  • Immediate-Early Proteins / genetics*
  • Immediate-Early Proteins / metabolism
  • Insulin-Like Growth Factor Binding Proteins*
  • Intercellular Signaling Peptides and Proteins*
  • Neovascularization, Physiologic / physiology
  • Ovarian Follicle / metabolism
  • Ovarian Follicle / physiology*
  • Ovary / blood supply
  • Ovary / cytology
  • RNA, Messenger / metabolism*
  • Swine


  • Biomarkers
  • Carrier Proteins
  • Growth Substances
  • Immediate-Early Proteins
  • Insulin-Like Growth Factor Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • insulin-like growth factor binding protein-related protein 1
  • Cyclin D1
  • Connective Tissue Growth Factor