Bovine Thecal Cells Secrete Transforming Growth Factor α and β

  • Derek K. Lobb
  • Jennifer H. Dorrington


The objective of the present study was to determine if the peptides secreted by bovine thecal cells influenced the growth and differentiation of bovine granulosa cells. Bovine thecal cells were cultured under serum-free conditions, the conditioned medium was concentrated and the peptides fractionated on a Bio-Gel P-60 column in 1.0 M acetic acid. Fractions were tested for their ability to stimulate [3H]thymidine incorporation into bovine granulosa cell DNA. Growth-promoting activity was located in the 6,000–9,000 and the 16,000 molecular weight fractions. The peak fractions inhibited FSH-induced aromatase activity in rat granulosa cells, indicating the presence of TGFα-like peptides. A growth inhibitory activity was observed in fractions with a molecular weight of approximately 25,000. The inhibitory activity had the molecular weight of TGFβ, and TGFβ was found to inhibit [3H]thymidine incorporation into bovine granulosa cell DNA. The presence of TGFβ-like activity was confirmed in two independent bioassays; stimulation of FSH-induced aromatase activity, and increased [3H]thymidine incorporation into rat granulosa cell DNA in the presence of FSH. In summary, bovine thecal cells secrete TGFα- and TGFβ-like activities that have opposing actions on the growth of bovine granulosa cells. The relative amounts of these growth factors may determine the rate of growth of granulosa cells during follicular development.


Granulosa Cell Thymidine Incorporation Follicular Development Aromatase Activity Thecal Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lussier J, Dufour JJ, Matton P. Growth rates of follicles in the bovine ovary [Abstract]. J Anim Sci 1983; 57(suppl 1):353.Google Scholar
  2. 2.
    Dorrington JH, McKeracher H, Garzo G, Skinner MK. Granulosa cell-theca cell interactions during follicular development. In: Labrie F, Proulx L, eds. Endocrinology. Amsterdam: Elsevier Science Publishers B.V., 1984:807–10.Google Scholar
  3. 3.
    Gospodarowicz D, Ill CR, Birdwell CR. Effects of fibroblast and epidermal growth factors on ovarian cell proliferation in vitro. I. Characterization of the response of granulosa cells to FGF and EGF. Endocrinology 1977; 100:1108–20.PubMedCrossRefGoogle Scholar
  4. 4.
    Adashi EY, Resnick CE. Antagonistic interactions of transforming growth factors in the regulation of granulosa cell differentiation. Endocrinology 1986; 1879–81.Google Scholar
  5. 5.
    Hammond JM, Baranao JLS, Skaleris D, Knight AB, Romanus JA, Rechter MM. Production of insulin-like growth factors by ovarian granulosa cells. Endocrinology 1985; 117:2553–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Hsu C-J, Holmes SD, Hammond JM. Ovarian epidermal growth factor-like activity. Concentrations in porcine follicular fluid during follicular enlargement. Biochem Biophys Res Commun 1987; 147:242–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Skinner MK, Lobb D, Dorrington JH. Ovarian thecal/interstitial cells produce an epidermal growth factor-like substance. Endocrinology 1987; 121:1892–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Lobb DK, Bendell JJ, Dorrington JH. Bovine thecal cells secrete a growth factor which stimulates granulosa cell proliferation [Abstract]. Biol Reprod 1986; 34(1):78.Google Scholar
  9. 9.
    Bendell JJ, Lobb DK, Chuma A, Gysler M, Dorrington JH. Bovine thecal cells secrete factor(s) that promote granulosa cell proliferation. Biol Reprod 1988; 38:790–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Lobb DK, Skinner MK, Dorrington JH. Rat thecal/interstitial cells produce a mitogenic activity that promotes the growth of granulosa cells. Mol Cell Endocrinol 1986; 55:209–17.CrossRefGoogle Scholar
  11. 11.
    Dorrington JH, Chuma AV, Bendell JJ. Transforming growth factor ß and follicle-stimulating hormone promote rat granulosa cell proliferation. Endocrinology 1988 (in press).Google Scholar
  12. 12.
    Gore-Langton RE, Dorrington JH. FSH induction of aromatase in cultured rat granulosa cells measured by a radiometric assay. Mol Cell Endocrinol 1981; 22:135–51.PubMedCrossRefGoogle Scholar
  13. 13.
    Massague J. Epidermal growth factor-like transforming growth factor. II. Interaction with epidermal growth factor receptors in human placenta membranes and A431 cells. J Biol Chem 1983; 258:13614–20.PubMedGoogle Scholar
  14. 14.
    Kobrin MS, Samsoondar J, Kudlow JE. a-Transforming growth factor secreted by untransformed bovine anterior pituitary cells in culture. II. Identification using a sequence-specific monoclonal antibody. J Biol Chem 1986; 261:14414–9.PubMedGoogle Scholar
  15. 15.
    Lobb DK, Kobrin MS, Kudlow JE, Dorrington JH (in preparation).Google Scholar
  16. 16.
    Ignotz RA, Kelly B, Davis RJ, Massague J. Biologically active precursor for transforming growth factor type α, released by retrovirally transformed cells. Proc Natl Acad Sci USA 1986; 83:6302–11.CrossRefGoogle Scholar
  17. 17.
    Skinner MK, Keski-Oja J, Osteen KG, Moses HL. Ovarian thecal cells produce transforming growth factor-ß which can regulate granulosa cell growth. Endocrinology 1987; 121:786–92.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Derek K. Lobb
    • 1
  • Jennifer H. Dorrington
    • 1
  1. 1.Banting and Best Department of Medical ResearchUniversity of TorontoTorontoCanada

Personalised recommendations