Skip to main content

Rapid, nongenomic steroid actions initiated at the cell surface: lessons from studies with fish

Abstract

In addition to the classic mechanism of steroid action mediated by binding to nuclear receptors, there is a growing body of evidence that steroids also exert rapid, nongenomic actions that are initiated at the cell surface by binding to specific steroid membrane receptors. However, the lack of information on the molecular structures of any steroid membrane receptors has impeded development of this alternative model of steroid hormone action. One of the best characterized models of nongenomic steroid action is the progestin induction of oocyte maturation (OM) in fish and amphibians via activation of plasma membrane progestin receptors (mPRs) on oocytes. Investigations of the marked changes in mPR abundance during OM in fishes have provided the first clear evidence of hormonal regulation of steroid membrane receptors and its physiological importance. Recently, a novel gene was discovered in the ovaries of spotted seatrout whose protein has the characteristics of an mPR and the intermediary in the progestin induction of oocyte maturation in this species. The putative mPR is also detected on seatrout sperm by Western blot analysis and is likely the mPR previously characterized in this species that mediates progestin initiation of sperm hyperactivity. Both structural and functional studies suggest the seatrout mPR is a G-protein coupled receptor (GPCR). Subsequently, thirteen structurally-related cDNAs were identified in other vertebrate species, and several of them were also shown to have characteristics of mPRs. The discovery of the molecular structure and likely orientation in the plasma membrane of this new class of steroid membrane receptors provides a plausible mechanistic explanation of how steroids acting at the cell surface can cause rapid intracellular responses. Membrane receptors for estrogens (mER) and androgens (mAR) have also been characterized in teleost gonads. In addition, the first clear evidence for endocrine disruption of a nongenomic steroid action by binding to a membrane steroid receptor was obtained with the seatrout mPR. Thus fish are valuable models for investigating nonclassical steroid actions and their interference by environmental contaminants.

This is a preview of subscription content, access via your institution.

References

  • Blackmore, P.F., Neulen, J., Lattanzio, F. and Beebe, S.J. 1991. Cell-surface binding sites for progesterone mediate calcium uptake in human sperm. J. Biol. Chem. 266: 18655–18659.

    Google Scholar 

  • Braun A. and Thomas, P. 2003. Androgens inhibit estradiol-17β synthesis in Atlantic croaker (Micropogonias undulatus) ovaries by a nongenomic mechanism initiated at the cell surface. Biol. Reprod. 69: 1642–1650.

    Google Scholar 

  • Das, S. and Thomas, P. 1999. Pesticides interfere with the nongenomic action of a progestogen on meiotic maturation by binding to its plasma membrane receptor on fish oocytes. Endocrinology 140: 1953–1956.

    Google Scholar 

  • Detweiler, C. and Thomas, P. 1998. Role of ions and ion channels in the regulation of Atlantic croaker sperm motility. J. Exp. Zool. 281: 139–148.

    Google Scholar 

  • Ghosh, S. and Thomas, P. 1995. Antagonistic effects of xenobiotics on steroid-induced final maturation of Atlantic croaker oocytes in vitro. Mar. Environ. Res. 39: 159–163.

    Google Scholar 

  • Hammes, S.R. 2003. The further redefining of steroid-mediated signaling. Proc. Natl. Acad. Sci. USA 100: 2168–2170.

    Google Scholar 

  • King, V,W., Ghosh, S., Thomas, P. and Sullivan, C.V. 1997. A receptor for the oocyte maturation-inducing hormone, 17, 20β, 21-trihydroxy-4-pregnen-3-one on ovarian membranes of striped bass. Biol. Reprod. 56: 266–271.

    Google Scholar 

  • Loomis, A.K. and Thomas, P. 2000. Effects of estrogens and xenoestrogens on androgen production by Atlantic croaker testes in vitro: evidence for a nongenomic action mediated by an estrogen membrane receptor. Biol. Reprod. 62: 995–1004.

    Google Scholar 

  • Maller, J.L. 1998. Recurring themes in oocyte maturation. Biology of the Cell 90: 453–460.

    Google Scholar 

  • Maller, J.L. 2003. Fishing at the cell surface. Science 300: 594–595.

    Google Scholar 

  • Miura, T.K., Yamauchi, K., Takahashi, H. and Nagahama, Y. 1992. The role of hormones in the acquisition of sperm motility in salmonid fish. J. Exp. Zool. 126: 89–96.

    Google Scholar 

  • Nadal, A., Ropero, A.B., Laribi, O., Maillet, M., Fuentes, E. and Soria, B. 2000. Nongenomic actions of estrogens and xenoestrogens by binding at a plasma membrane receptor unrelated to estrogen receptor alpha and estrogen receptor beta. Proc. Natl. Acad. Sci. USA 97: 11603–11608.

    Google Scholar 

  • Nagahama, Y., Yoshikuni, M., Yamashita, M. And Tanaka, M. 1994 Regulation of oocyte maturation in fish. Pp. 393–439. In: Sherwood N.M, Hew C.L, editors. Fish Physiology Vol. XIII. San Diego, Academic Press.

    Google Scholar 

  • Patiño, R. and Thomas, P. 1990 Characterization of membrane receptor activity for 17β, 20β, 21-trihydroxy-4-pregnen-3-one in ovaries of spotted seatrout (Cynoscion nebulosus). Gen. Comp. Endocrinol. 78: 204–217.

    Google Scholar 

  • Pickford, D.B. and Morris, I.D. 1999. Effects of endocrinedisrupting contaminants on amphibian oogenesis: methoxychlor inhibits progesterone-induced maturation of Xenopus laevis oocytes in vitro. Environ, Hlth. Perspect. 107: 285–92.

    Google Scholar 

  • Rahman, M., Ohta, K., Yoshikuni, M., Nagahama, Y., Chuda, H. and Matsuyama, M. 2002. Characterization of ovarian membrane receptor for 17, 20β-dihydroxy-4-pregnen-3-one, a maturationinducing hormone in yellowtail, Seriola quinqueradiata. Gen Comp Endocrinol. 127: 71–79.

    Google Scholar 

  • Revelli, A., Massobrio, M. and Tesarik, J. 1998. Nongenomic actions of steroid hormones in reproductive tissues. Endocr. Rev. 19: 3–17.

    Google Scholar 

  • Ruehlmann, D.O., Steinert, J.R., Valverde, M.A., Jacob, R., and Mann, G.E. 1998. Environmental estrogenic pollutants induce acute vascular relaxation by inhibiting L-Type Ca2 channels in smooth muscle cells. FASEB Journal. 12: 613–619.

    Google Scholar 

  • Thomas, P. 1994. Hormonal control of final oocyte maturation in sciaenid fishes. In: K.G., Davey., R.E. Peter, S.S. Tobe, editors. Pp. 619–625. Perspectives in Comparative Endocrinology, Ottawa National Research Council of Canada.

  • Thomas, P. 2000a. Nuclear and membrane steroid receptors and their functions in teleost gonads. In: Proceedings of the Sixth International symposium on the Reproductive Physiology of Fish, Pp. 149–156. Edited by B. Norberg, O.S. Kjesbu, G.L.Taranger, E. Andersson and S.O. Stefansson, Institute of Marine Research and University of Bergen, Bergen, Norway.

    Google Scholar 

  • Thomas, P. 2000b. Chemical interference with the genomic and nongenomic actions of steroids in fishes: role of receptor binding. Mar. Environ. Res. 50: 127–134.

    Google Scholar 

  • Thomas P., Breckenridge-Miller, D. and Detweiler, C. 1997 Binding characteristics and regulation of the 17β, 20β, 21-trihydroxy-4-pregen-3-one (20β-S) receptor on testicular and sperm membranes of spotted seatrout (Cynocscion nebulosus). Fish Physiol. Biochem. 17: 109–117.

    Google Scholar 

  • Thomas, P., Breckenridge-Miller, D. and Detweiler, C. 1998. The teleost sperm membrane progestogen receptor: interactions with xenoestrogens. Marine Environmental Research 46: 163–167.

    Google Scholar 

  • Thomas, P., Pinter, J. and Das, S. 2001 Upregulation of the maturation-inducing steroid membrane receptor in spotted seatrout ovaries by gonadotropin during oocyte maturation and its physiological significance. Biol. Reprod. 64: 21–29.

    Google Scholar 

  • Thomas, P. and Das, S. 1997. Correlation between binding affinities of C21 steroids for the maturation-inducing steroid membrane receptor in spotted seatrout ovaries and their agonist and antagonist activities in an oocyte maturation bioassay. Biol. Reprod. 57: 999–1007.

    Google Scholar 

  • Thomas, P. and Patiño, R. 1991. Changes in 17α, 20β, 21-trihydroxy-4-pregnen-3-one membrane receptor concentrations in ovaries of spotted seatrout during final oocyte maturation. In: A.P. Scott, J. Sumpter, D. Kime, M.S. Rolge, editors. Proceedings of the Fourth International Symposium on the Reproductive Physiology of Fish. Pp. 122–124. Sheffield, UK: University of East Anglia.

    Google Scholar 

  • Thomas, P., Zhu, Y. and Pace, M. 2002. Progestin membrane receptors involved in the meiotic maturation of teleost oocytes: a review with some new findings. Steroids 67: 511–517.

    Google Scholar 

  • Thomas, P., Zhu, Y. and Pang, Y.F. 2003. Current knowledge of the nature of progestin and estrogen membrane receptors in fish gonads. In: Identities of Steroid Membrane Receptors, pp. 131–138. Edited by C.S.Watson. Kluwer Academic Publishers, Boston.

    Google Scholar 

  • Watson, C.S. and Gametchu, B. 1999. Membrane-initiated steroid actions and the proteins that mediate them. Proc. Soc. Exp. Biol. Med. 220: 9–19.

    Google Scholar 

  • Yoshikuni M., Shibata N. and Nagahama Y. 1993 Specific binding of [3H]17α, 20β-dihydroxy-4-pregnen-3-one to oocyte cortices of rainbow trout (Oncorhynchus mykiss). Fish Physiol. Biochem. 1993; 11: 15–24.

    Google Scholar 

  • Yoshikuni, M. and Nagahama, Y. 1994. Involvement of an inhibitory G-protein in the signal transduction pathway of maturationinducing hormone (17α, 20β, 21-dihydroxy-4-pregnen-3-one) action in rainbow trout (Oncorhynchus mykiss) oocytes. Dev. Biol. 16: 615–622.

    Google Scholar 

  • Zhu, Y., Rice, C.D., Pang, Y., Pace, M. and Thomas, P. 2003a. Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes. Proc. Natl. Acad. Sci. USA 100: 2231–2236.

    Google Scholar 

  • Zhu, Y, Bond, J. and Thomas, P. 2003b. Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor. Proc. Natl. Acad. Sci. USA 100: 2237–2242.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Thomas, P. Rapid, nongenomic steroid actions initiated at the cell surface: lessons from studies with fish. Fish Physiology and Biochemistry 28, 3–12 (2003). https://doi.org/10.1023/B:FISH.0000030461.35242.57

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:FISH.0000030461.35242.57

  • steroid membrane receptors
  • nongenomic steroid actions
  • oocyte maturation
  • sperm motility
  • progestin membrane receptors
  • hormonal regulation steroid membrane receptors
  • endocrine disruption