Glucocorticoid Receptors and Steroid Sensitivity in Normal and Neoplastic Human Lymphoid Tissues: A Review Françoise Homo-Delarche Cancer Res 1984;44:431-437. Published online February 1, 1984.
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[CANCER RESEARCH 44, 431-437,
February 1984]
Glucocorticoid Receptors and Steroid Sensitivity in Normal and Neoplastia Human Lymphoid Tissues: A Review1 FrançoiseHomo-Delarche INSERM U7, Physiology and Pharmacology, Hôpital Necker, 161 rue de Sèvres, 75015 Paris, France
This paper presents a critical review of GR2 determination as
Abstract The determination of estrogen and progesterone receptors in breast cancer has been shown to be useful in predicting the response to endocrine therapy. Given their well-known inhibitory effects on lymphoid tissue, glucocorticoids have been used widely in the treatment of leukemia. Given these facts, over the last 10 years, several investigators have measured the number of glucocorticoid receptors in normal and neoplastic lymphoid tissue to see whether their number correlated with glucocorticoid responsiveness in vitro or in vivo. No clear correlation could be established between the level of glucocorticoid receptor and the in vitro action of steroids in normal and neoplastic lymphoid tissue. In contrast, attempts to correlate glucocorticoid receptor levels in acute lymphocytic leukemia to in vivo steroid respon siveness and immunological type using the whole-cell-binding assay for receptor determination and selecting the patients ac cording to age and immunological criteria have been more suc cessful.
Introduction It has been known for a long time that glucocorticoids exert many physiological and pharmacological effects on mammalian lymphoid tissues. In vivo administration of corticosteroids or adrenalectomy has been shown to induce marked changes in the size of lymphoid organs as well as in lymphocyte circulation and to alter many immunological reactions (11 ). In vitro, gluco corticoids are generally considered as catabolic agents that induce an inhibition of membrane transport and macromolecular synthesis leading to an arrest of cell growth, sometimes accom panied by cell lysis (54). These compounds are also able to modify several immunological functions in vitro (1). These widespread effects on lymphoid cell metabolism and function constitute the basis for the use of glucocorticoid hor mones in the treatment of a wide variety of immunological and inflammatory diseases as well as in the treatment of lymphoid cell neoplasias. According to the classical mechanism of steroid hormone action, which includes a preliminary step of interaction of the steroid with cytoplasmic receptors (53), numerous studies have been devoted to the question of whether or not the receptor content of lymphoid cells may be representative of the in vitro or in vivo sensitivity. The different methods used to measure steroid receptor levels as well as in vitro and in vivo sensitivity are listed in Table 1. 1Part of this work was supported by Grant 76-7-1669 from DGRST, by Grant 58-78-90 from INSERM, and by the National Cancer Institute-INSERM Collaborative Agreement on Hormonal Regulation and Cancer (1976/1977). Received May 5,1983; accepted October 6.1983.
FEBRUARY
an index of steroid sensitivity in normal and leukemic human lymphoid tissue. Normal human lymphoid cells Although many studies have attempted to determine the ef fects of glucocorticoids on leukemic lymphoid tissues, only a few have actually related the extent of steroid action in normal human lymphoid cells to the level of GR. As shown in Table 2, the number of GR was determined by whole-cell assay in children's thymocytes and bone marrow as well as in adult blood and lymph node lymphocytes in a number of studies (5,13,31,32,36,43,46, 56,58,63,70). It is apparent that the number of binding sites found in blood lymphocytes is very similar in the various reports and ranged from 3 to 7000 sites per cell with a «
