Skip to main content
SpringerLink
Log in

Acute, nongenomic actions of the neuroactive gonadal steroid, 3α-hydroxy-4-pregnen-20-one (3αHP), on FSH release in perifused rat anterior pituitary cells

  • Original Articles
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

We have previously shown that the gonadal and neurosteroid, 3α-hydroxy-4-pregnen-20-one (3αHP), can selectively suppress gonadotrophin-releasing hormone (GnRH) induced follicle-stimulating hormone (FSH) release from static cultures of anterior pituitary cells during a 4-h incubation period. The actions appeared to be at the level of the gonadotroph membrane and the cell signaling pathway involving Ca2+ and protein kinase C (PKC). In order to investigate further if the effects of 3αHP on FSH release are generated by nongenomic mechanisms, we monitored the short-term effects of 3αHP using dispersed anterior pituitary cells in a low dead-volume perifusion system with short (≤5 min) exposures to the steroid. Pulses of GnRH (10−8 or 10−7 M) lasting 2–5 min resulted in marked peaks of FSH release, and the variation in FSH amounts released from the cells in a particular column were minimal if the interval between successive GnRH pulses was at least 3–4 h. A 5-min pulse of 3αHP (10−9 M) administered simultaneously with the GnRH pulse suppressed GnRH-induced FSH release. On the other hand, similar treatment with the stereoisomer 3β-hydroxy-4-pregnen-20-one (3βHP), had no effect, but progesterone and estradiol pulses augmented the GnRH-induced FSH release. Pretreatment of cells with a 5-min pulse of 3αHP, at 120, 60, or 30 min prior to a GnRH pulse suppressed the GnRH-induced FSH release. The suppression of GnRH-induced FSH release by 3αHP was only partial if the start of the 3αHP pulse occurred 0.5 or 1.0 min after the start of the GnRH pulse, and no suppression occurred if the start of the 3αHP pulse was delayed by 2–5 min. The FSH release elicited by 5-min pulses of the Ca2+ ionophore A23187, the Ca2+ agonist BAYK8644, the PKC activator phorbol 12-myristate 13-acetate (PMA), or phospholipase C (PLC) was suppressed by simultaneous pulses of 3αHP. The suppression of FSH release by 3αHP appeared to bestereospecific, since no suppression was observed with 5α-pregnane-3,20-dione (5αP) or 3α-hydroxy-5α-pregnan-20-one (5αP3α). In separate experiments, cells were treated with pulses of BSA conjugates of 3αHP, 3βHP, or progesterone; the 3αHP-BSA, but not the 3βHP-BSA or the progesterone-BSA, suppressed the GnRH-induced release of FSH. The results of this study provide the first evidence that 3αHP exerts immediate (nongenomic) and direct effects on GnRH-induced FSH release by interacting at the level of the pituitary gonadotroph membrane and the phosphoinositol cell signaling cascade involving Ca2+.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Clapper, D. L. and Conn, P. M. (1985).Biol. Reprod. 32, 269–278.

    Article  PubMed  CAS  Google Scholar 

  2. Conn, P. M., Huckle, W. R., Andrews, W. V., and McArdle, C. A. (1987).Rec. Prog. Horm. Res. 43, 29–68.

    PubMed  CAS  Google Scholar 

  3. Stojikovic, S. S. and Catt, K. J. (1995).J. Neuroendocrinol. 7, 739–757.

    Article  Google Scholar 

  4. Krey, L. C. and Kamel, F. (1990).Mol. Cell. Endocrinol. 70, 21–29.

    Article  PubMed  CAS  Google Scholar 

  5. Kellom, T. A. and O'Conner, J. L. (1991).J. Steroid Biochem. Molec. Biol. 39, 501–511.

    Article  PubMed  CAS  Google Scholar 

  6. Ravindra, R., and Aronstam, R. S. (1992).Acta Endocrinol. 126, 345–349.

    PubMed  CAS  Google Scholar 

  7. Counis, R. and Jutisz, M. (1991).Trends Endocrinol. Metab. 2, 181–187.

    Article  PubMed  CAS  Google Scholar 

  8. Dhanvantari, S. and Wiebe, J. P. (1994).Endocrinology 134, 371–376.

    Article  PubMed  CAS  Google Scholar 

  9. Wiebe, J. P., Dhanvantari, S., Watson, P. H., and Hang, Y. (1994).Endocrinology 134, 377–382.

    Article  PubMed  CAS  Google Scholar 

  10. Weiss, J. and Jameson, J. L. (1993).TEM 8, 265–269.

    Google Scholar 

  11. Hansen, J. R., McArdle, C. A., and Conn, P. M. (1987).Mol. Endocrinol. 1, 808–815.

    Article  PubMed  CAS  Google Scholar 

  12. McArdle, C. A., and Poch, A. (1992).Endocrinology 130, 3567–3574.

    Article  PubMed  CAS  Google Scholar 

  13. Stojilkovic, S. S., Iida, T., Cesnjaj, M., and Catt, K. J. (1992).Endocrinology 131, 2821–2828.

    Article  PubMed  CAS  Google Scholar 

  14. Liu, T-C. and Jackson, G. L. (1984).Proc. Soc. Exp. Biol. Med. 249, E165-E174.

    Google Scholar 

  15. Kotsuji, F., Winters, S. J., Attardi, B., Keeping, H. S., Oshima, H., and Troen, P. (1988).Endocrinology 123, 2683–2689.

    Article  PubMed  CAS  Google Scholar 

  16. Ortman, O., Wassmann, D., Stojikovic, S. S., Catt, K. J., Schulz, K-D., and Emons, G. (1993).Endocrinology 133, 2632–2638.

    Article  Google Scholar 

  17. Wood, P. H. and Wiebe, J. P. (1989).Endocrinology 134, 377–382.

    Google Scholar 

  18. Wiebe, J. P., de Gannes, G. C., and Dallaire, M. J. (1994).Biol. Reprod. 50, 956–964.

    Article  PubMed  CAS  Google Scholar 

  19. Wiebe, J. P., Boushy, D., and Wolfe, M. (1997).Brain Res. in press.

  20. Li, P-H. S. (1993).Life Sci. 53, 141–151.

    Article  PubMed  CAS  Google Scholar 

  21. Liu, T-C. and Jackson, G. L. (1988).Biol. Reprod. 39, 787–796.

    Article  PubMed  CAS  Google Scholar 

  22. Frawley, L. S. and Neill, J. D. (1984).Endocrinology 114, 659–663.

    Article  PubMed  CAS  Google Scholar 

  23. Kamel, F. and Krey, L. C. (1982).Mol. Cell Endocrinol. 32, 151–164.

    Article  Google Scholar 

  24. Kim, K. and Ramirez, V. D. (1982).Endocrinology 111, 750–757.

    Article  PubMed  CAS  Google Scholar 

  25. Drouin, J. and Jabrie, F. (1981).Endocrinology 108, 52–57.

    Article  PubMed  CAS  Google Scholar 

  26. Morrow, A. L. Pace, J. R., Purdy, R. H., and Paul, S. M. (1990).Molec. Pharmacol. 37, 263–270.

    CAS  Google Scholar 

  27. Ortmann, O., Stojilkovic, S. S., Cesnjaj, M., Emons, G., and Catt, K. J. (1992).endocrinology 131, 1565–1567.

    Article  PubMed  CAS  Google Scholar 

  28. Dayanithi, G. and Tapia-Arancibia, L. (1996).J. Neurosci. 16, 130–136.

    PubMed  CAS  Google Scholar 

  29. Ke, F-C. and Ramirez, V. D. (1987).Neuroendocrinology 45, 514–517.

    Article  PubMed  CAS  Google Scholar 

  30. Koch, B., Luz-Bucher, B., Briaud, B., and Mialhe, C. (1987).J. Endocrinol. 79, 215–222.

    Article  Google Scholar 

  31. Bression, D., Michard, M., Le Dafniet, M., Pagesy, P., and Peillon, F. (1986).Endocrinology 119, 1048–1051.

    Article  PubMed  CAS  Google Scholar 

  32. Moore, F. L., Orchinik, M., and Lowry, C. (1995).Receptor 5, 21–28.

    PubMed  CAS  Google Scholar 

  33. Mermelstein, P. G., Becker, J. B., and Surmeier, D. J. (1996).J. Neurosci. 16, 595–604.

    PubMed  CAS  Google Scholar 

  34. Mendoza, C., and Tesarik, J. (1993).FEBS Lett. 330, 57–60.

    Article  PubMed  CAS  Google Scholar 

  35. Wehling, M. (1995).Steroids 60, 153–156.

    Article  PubMed  CAS  Google Scholar 

  36. Wiebe, J. P. and Kavaliers, (1988).Brain Res. 461, 150–157.

    Article  PubMed  CAS  Google Scholar 

  37. Vincens, M., Shu, C., Moguilewsky, M., and Philibert, D. (1989).Eur. J. Pharmacol. 168, 15–21.

    Article  PubMed  CAS  Google Scholar 

  38. Wiebe, J. P. (1997).Rec. Prog. Horm. Res. 52, 71–101.

    PubMed  CAS  Google Scholar 

  39. O'Conner, J. L., Clary, A. R., and Kellom, T. A. (1988).Life Sci. 42, 61–72.

    Article  PubMed  Google Scholar 

  40. Greeley, G. H., Allen, M. B., and Mahesh, V. B. (1978).Neuroendocrinology 18, 233–241.

    Article  Google Scholar 

  41. Goodman, R. L. (1978).Endocrinology 102, 142–150.

    Article  PubMed  CAS  Google Scholar 

  42. Bourne, G. A., and Baldwin, D. M. (1987).Am. J. Physiol. 253, 290–295.

    Google Scholar 

  43. Drouva, S. V., Gorenne, I., Laplante, E., Rérat, E., Enjalbert, A., and Kordon, C. (1990).Endocrinology 126, 536–544.

    Article  PubMed  CAS  Google Scholar 

  44. Katayama, T. and Conn, P. M. (1994).Endocrinology 134, 119–125.

    Article  PubMed  CAS  Google Scholar 

  45. Conn, P. M., Ganong, B. R., Ebeling, J., Staley, D., Neidel, J., Bell, R. M. (1985).Biochem. Biophys. Res. Commun. 126, 532–538.

    Article  PubMed  CAS  Google Scholar 

  46. Naor, Z., Capponi, A. M., Rossier, M. F., Ayalon, D., and Limor, R. (1988).Mol. Endocrinol. 2, 512–520.

    Article  PubMed  CAS  Google Scholar 

  47. Mendoza, C., Soler, A., and Tesarik, J. (1995).Biochem. Biophys. Res. Commun. 210, 518–523.

    Article  PubMed  CAS  Google Scholar 

  48. Wiebe, J. P., Deline, C., Buckingham, K. D., Dove, V., and Stothers, J. R. (1985).Steroids 45, 39–51.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. H. R. M. Laboratory, University of Western Ontario, B & G Building, Room 344, N6A 5B7, London, Ontario, Canada

    Christine A. Beck, Marni Wolfe, Leanne D. Murphy & John P. Wiebe

Authors
  1. Christine A. Beck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marni Wolfe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leanne D. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John P. Wiebe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John P. Wiebe.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beck, C.A., Wolfe, M., Murphy, L.D. et al. Acute, nongenomic actions of the neuroactive gonadal steroid, 3α-hydroxy-4-pregnen-20-one (3αHP), on FSH release in perifused rat anterior pituitary cells. Endocr 6, 221–229 (1997). https://doi.org/10.1007/BF02820496

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02820496

Key Words

Search

Navigation