Summary
Events related to the very early steps of steroid hormone action are reviewed, after a brief exposé of the methods used for the measurement and calculation of protein-steroid interactions.
A list of steroid binding plasma proteins is given, and their physiological variations and possible role(s) are discussed. The mechanism of entry of steroids into target cells is then considered, especially the possibility of a protein mediated step. The metabolism of steroid hormone in target cells and its physiological significance are discussed, especially with reference to androgens in prostate, levator ani muscle and hypothalamus.
No receptor of steroid hormone has yet been discovered if defined as the last entity with which the active steroid interacts before action is initiated. However, in the target tissues of steroid hormones, specific proteins have been detected (termedreceptors) with properties that are compatible with an essential if not an obligatory role in steroid action. The properties ascribed to the cytosolreceptors of different steroid hormones in various tissues, their binding properties, and their quantitative variations are reported. The transformation or activation ofreceptor after binding of the hormone is related to its transfer to the nucleus. The question posed by the recent observations on Non Histone Chromatin estrogen binding protein and of the “insoluble” nuclearreceptor are discussed.
Finally, a series of experiments are reviewed, dealing more specifically with the increase of protein and RNA synthesis in tissues in which steroids promote growth (i.e. estradiol in uterus). The concept of a cascade phenomenon is reported, including the early synthesis of KIP (Key Intermediary Protein(s)) which would be responsible for the secondary amplification of the response. It is discussed in connection with the present (and insufficient) knowledge ofreceptors and transcription machinery.
Similar content being viewed by others
References
Baulieu, E. E., Alberga, A., Jung, I., Lebeau, M. C., Mercier-Bodard, C., Milgrom, E., Raynaud, J. P., Raynaud-Jammet, C., Rochefort, H., Truong, H. and Robel, P., Metabolism and protein binding of sex steroids in target organs: An approach to the mechanism of hormone action. Rec. Progr. in Horm. Res., 27, 351–419 (1971).
Baulieu, E. E., Raynaud, J. P. and Milgrom, E., Measurement of steroid binding proteins. Acta Endocr., suppl. 147, 64, 104–121 (1970).
Truong, H. and Baulieu, E. E., Interaction of uterus cytosol receptor with estradiol. Equilibrium and kinetic studies. Biochim. Biophys. Acta 237, 167–172 (1971).
Westphal, U., Steroid Protein Interactions, Monographs on Endocrinology 4, (1971) Springer Verlag, Berlin, Heidelberg, New York.
Mercier-Bodard, C., Alfsen, A. and Baulieu, E. E., Sex steroid binding plasma protein (SBP). Acta Endocrinol., suppl. 147, 64, 204–224 (1970).
Raynaud, J. P., Mercier-Bodard, C. and Baulieu, E. E., Rat estradiol binding plasma protein (EBP). Steroids, 18, 767–788 (1971).
Mahoudeau, J. A. and Corvol, P., Rabbit testosterone-binding globulin. I. Physico-chemical properties. Endocrinology 92, 1113–1119 (1973).
Milgrom, E., Allouch, P., Atger, M. and Baulieu, E. E., Progesterone-binding plasma protein of pregnant guinea pig. Purification and characterization. J. Biol. Chem. 248, 1106–1114 (1973).
French, F. S. and Ritzen, E. M., A high-affinity-androgen-binding protein (ABP) in rat testis: evidence for secretion into efferent duct fluid and absorption by epididymis. Endocrinology, 93, 88–95 (1973).
Milgrom, E. and Baulieu, E. E. Progesterone in uterus and plasma. I. Binding in rat uterus 105,000 g supernatant. Endocrinology 87, 276–287 (1970).
Hellman, L., Nakada, F. M., Curti, J., Weitzman, E. D., Kream, J., Roffwarg, H., Ellman, S., Fukushima, D. K. and Gallagher, T. F., Cortisol is secreted episodically by normal man. J. Clin. Endocr. Metab. 30, 411–422 (1970).
Milgrom, E., Atger, M. and Baulieu, E. E., Studies on estrogen entry into uterine cells and on estradiol-receptor complex attachment to the nucleus. Is the entry of estrogen into uterine cells a protein-mediated process? Biochim. Biophys. Acta 320, 267–283 (1973).
Jensen, E. V. and Jacobson, H. I., Basic guides to the mechanism of estrogen action. Rec. Progr. Horm. Res. 18, 387–414 (1962).
Talalay, P. and Williams-Ashman, H. G., I. Mechanisms of hormone action. Participation of steroid hormone in the enzymatic transfer of hydrogen. Rec. Progr. Horm. Res. 16, 1–47 (1960).
Ofner, P., Effects and metabolism of hormones in normal and neoplastic prostate tissue. Vitamins and Hormones 26, 237–291 (1968).
Baulieu, E. E. and Mauvais-Jarvis, P., Studies on testosterone metabolism. I. Conversion of testosterone-17α-3H to 5α- and 5β-androstane-3α, 17β-diol-17α-3H: a new 17β-hydroxyl pathway. J. Biol. Chem., 239, 1569–1577 (1964).
Bruchovski, N. and Wilson, J. D., The conversion of testosterone to 5α-androstan-17β-ol-3-one by rat prostatein vivo andin vitro. J. Biol. Chem. 243, 2012–2021 (1968).
Wilson, J. D. and Gloyna, R. E., The intranuclear metabolism of testosterone in the accessory organs of reproduction. Rec. Progr. Horm. Res. 26, 309–336 (1970).
Anderson, K. M. and Liao, S., Selective retention of dihydrotestosterone by prostatic nuclei. Nature 219, 277–279 (1968).
Baulieu, E. E., Lasnitzki, I. and Robel, P., Metabolism of testosterone and action of metabolites on prostate glands grown in organ culture. Nature, 219, 1155–1156 (1968).
Robel, P. and Baulieu, E. E., Irrigation continue appliquée á la culture organotypique C.R. Acad. Sci. Paris 274, 3295–3298 (1972).
Moore, R. J. and Wilson, J. D., Localization of the reduced-nicotinamide adenine dinucleotide phosphate: Δ4-3-testosteroid 5α-oxydoreductase in the nuclear membrane of the rat ventral prostate. J. Biol. Chem. 247, 958–967 (1972).
Roy, A. B., The steroid 5α-reductase activity of rat liver and prostate. Biochimie 53, 1031–1040 (1971).
Robel, P., Lasnitzki, I. and Baulieu, E. E., Hormone metabolism and action: testosterone and metabolites in prostate organ culture. Biochimie 53, 81–96 (1971).
Baulieu, E. E., Corpéchot, C., Dray, F., Emiliozzi, R., Lebeau, M. C., Mauvais-Jarvis, P. and Robel, P., An adrenal-secreted “Androgen”: Dehydroisoandrosterone sulfate. Its metabolism and a tentative generalization on the metabolism of other steroid conjugates in man. Rec. Progr. in Horm. Res. 21, 411–500 (1965).
VandeWiele, R., MacDonald, P., Gurpide, E. and Lieberman, S., Studies on secretion and interconversion of the androgens. Rec. Progr. Horm. Res. 19, 275–310 (1963).
Bullock, L. P., Bardin, C. W. and Ohno, S. The androgen insensitive mouse: absence of intramolecular androgen retention in the kidney. Biochem. Biophys. Res. Commun. 44, 1537–1543 (1971).
Naftolin, F., Ryan, K. V. and Petro, Z., Aromatization of androstenedione by the diencephalon. J. Clin. Endocr. 33, 368–370 (1971).
Zanisi, M., Motta, M. and Martini, L., Inhibitory effects of 5α-reduced metabolites of testosterone on gonadotrophin secretion. J. Endocr. 56, 315–316 (1973).
Talwar, G. P., Segal, S. J., Evans, A. and Davidson, O. W., The binding of the estradiol in the uterus: a mechanism for derepression of RNA synthesis. Proc. Natl. Acad. Sci. U.S. 52, 1059–1066 (1964).
Toft, D. and Gorski, J., A receptor molecule for oestrogen isolation from the rat uterus and preliminary characterization. Proc. Natl. Acad. Sci. U.S. 55, 1574–1581 (1966).
Raspé, G. (ed.): Steroid Hormone Receptors Advances in the Biosciences 7, Pergamon Press-Vieweg, Oxford (1971).
Sica, V., Nola, E. Parikh, I., Puca, G. A. and Cuatrecasas, P., Affinity chromatography and the purification of estrogen receptors. J. Biol. Chem. 248, 6543–6558 (1973).
Truong, H., Geynet, C., Millet, C., Soulignac, O., Bucourt, R., Vignau, M., Torelli, V. and Baulieu, E. E., Purification of oestradiolreceptor by affinity chromatography. Representative experiments. FEBS Letters 35, 289–294 (1973).
Milgrom, E., Luu Thi and Baulieu, E. E., Control mechanisms of steroid hormonereceptors in the reproductive tract. Acta Endocrinol. suppl. 180, 380–403 (3) (1973).
Mester, I., Martel, D., Psychoyos, A. and Baulieu, E. E., Hormonal control of oestrogen receptor in the uterus and receptivity for ovo-implantation in the rat. Nature. 250, 776–778 (1974).
Baulieu, E. E., Antiprogesterone effect and mid-cycle (periovulatory) contraception. European Abst. 944 in press (1974).
Geynet, C., Millet, C., Truong, H. and Baulieu, E. E., Estrogens and antiestrogens. Gyn. Invest. P. O. Hubinont, S. M. Hendeles, P. Preumont, Ed., (S. Karger, Basel), 3, 2–29 (1972).
Fanestil, D. D. and Edelman, I. S., Characteristics of the renal nuclear receptors for aldosterone. Proc. Natl. Acad. Sci. U.S. 56, 872–879 (1966).
Brecher, P. I., Vigersky, R., Wotiz, H. S. and Wotiz, H. H., Anin vitro system for the binding of oestradiol to rat uterine nuclei. Steroids 10, 635–651 (1967).
Jensen, E. V., Suzuki, T., Kawashima, T., Stumpf, W. E., Jungblut, P. W. and DeSombre, E. E., A two-step mechanism for the interaction of estradiol with rat uterus. Proc. Natl. Acad. Sci. U.S. 59, 632–638 (1968).
Gorski, J., Toft, D., Shyamala, G., Smith, D. and Notides, A., Hormone receptors: studies on the interaction of estrogen with the uterus. Rec. Progr. Horm. Res. 24, 45–80 (1968).
Milgrom, E., Atger, M. and Baulieu, E. E., Acidophilic activation of steroid hormone receptors. Biochemistry 12, 5198–5205 (1973).
Higgins, S. J., Rousseau, G. G., Baxter, J. and Tomkins, G. M., Early events in glucocorticoid action. J. Biol. Chem. 248, 5866–5872 (1973).
O'Malley, B. W., Spelsberg, T. C., Schrader, W. T., Chytil, F. and Steggles, A. W., Mechanism of interaction of a hormone receptor complex with the genome of an eukaryotic target cell. Nature 235, 141–144 (1972).
Raynaud-Jammet, C. and Baulieu, E. E., Action de l'oestradiolin vitro: augmentation de la biosynthèse d'ARN dans les noyaux utérins; C.R. Acad. Sci. Paris 268, 3211–3214 (1969).
Arnaud, M., Beziat, Y., Guilleux, J. C., Hough, A. and Mousseron-Canet, M., Les récepteurs de l'oestradiol dans l'utérus de génisse. Stimulation de la biosynthèse de RNAin vitro. Biochim. Biophys. Acta, 232, 117–131 (1971).
Mohla, S., DeSombre, E. R. and Jensen, E. V., Tissue specific stimulation of RNA synthesis by transformed estradiol-receptor complex. Biochem. Biophys. Res. Com. 42, 661–667 (1972).
Alberga, A., Massol, N., Raynaud, J. P. and Baulieu, E. E., Estradiol binding of exceptionally high affinity by a non histone chromatin protein fraction. Biochemistry, 10, 3835–3843 (1971).
Lebeau, M. C., Massol, N. and Baulieu, E. E., An insoluble receptor for oestrogens in the “residual” nuclear proteins of chick liver. Eur. J. Biochem. 36, 294–300 (1973).
Mueller, G. C., Herranen, A. M. and Jervell, K. F., Studies on the mechanism of action of estrogens. Rec. Progr. Horm. Res. 14, 95–140 (1958).
Gorski, J., Early estrogen effects on the activity of uterine ribonucleic acid polymerase. J. Biol. Chem., 239, 889–892 (1964).
Gorski, J., Noteboom, W. D. and Nicolette, J. A., Estrogen control of the synthesis of RNA and protein in the uterus. J. Cell. Comp. Physiol. suppl. 1, vol. 66, 91–98 (1965).
Baulieu, E. E., Alberga, A., Raynaud-Jammet, C. and Wira, C., New look at the very early steps of oestrogen action in uterus. Nature New Biol. 236, 236–239 (1972).
Tomkins, G. M., Gelehrter, T. D., Granner, D., Martin, D. Jr., Samuels, H. and Thompson, E. B., Control of specific gene expression in higher organisms. Science 166, 1474–1480 (1969).
Nicolette, J. A. and Mueller, G. C.,In vitro regulation of RNA polymerase in estrogen-treated uteri. Biochem. Biophys. Res. Com. 24, 851–857 (1966).
Raynaud-Jammet, C., Catelli, M. G. and Baulieu, E. E., Inhibition byα-amanitin of the estradiol-induced increase inα-amanitin insensitive RNA polymerase in immature rat uterus. FEBS Letters, 22, 93–96 (1972).
Mueller, G. C., Vonderhaar, B., Kim, U. H. and Le Mahieu, M., Estrogen action: an inroad to cell biology. Rec. Progr. Horm. Res. 28, 1–49 (1972).
Notides, A. and Gorski, J., Estrogen-induced synthesis of a specific uterine protein. Proc. Natl. Acad. Sci. U.S. 56, 230–235 (1966).
Wira, C. R. and Baulieu, E. E., Synthèse protéique stimuléein vitro par l'oestradiol dans l'utérus de ratte. C. R. Acad. Sci. Paris 273, 218–221 (1971).
Katzenellenbogen, B. S. and Gorski, J., Estrogen actionin vitro. J. Biol. Chem. 247, 1299–1305 (1972).
Wira, C. R. and Baulieu, E. E., Réponse ribonucléique précoce de l'utérus à l'oestradiol,in vivo etin vitro. C. R. Acad. Sci. Paris 274, 73–76 (1972).
Tomkins, G. M. and Maxwell, E. S., Some aspects of steroid hormone action. Annual Rev. Biochem. 32, 677–708 (1963).
Munck, A., Glucocorticoid inhibition of glucose uptake by peripheral tissues: old and new evidence, molecular and physiological significance. Perspectives Biol. Med. 14, 265–273 (1971).
Lee, K. L., Reel, J. R. and Kenney, F. T., Regulation of tyrosineα-ketoglutarate transaminase in rat liver. J. Biol. Chem. 245, 5806–5812 (1970).
Rochefort, H. and Baulieu, E. E., Effect of KCl, CaCl2, temperature and oestradiol on the uterine cytosolreceptor of oestradiol. Biochimie 53, 893–907 (1971).
Author information
Authors and Affiliations
Additional information
An invited article
Lab Hormones, 94270-BICETRE, France
Rights and permissions
About this article
Cite this article
Baulieu, EE. Some aspects of the mechanism of action of steroid hormones. Mol Cell Biochem 7, 157–174 (1975). https://doi.org/10.1007/BF01731406
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01731406