| Title | Intracrinology and hormone-dependent cancers | |
| Authors | Van Luu-The, Jacques Simard, Claude Labrie, Alain Bélanger and Fernand Labrie
MRC Group in Molecular Endocrinology, CHUL Research Center and Laval University, Quebec, Canada G1V 4G2 |
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| Citation | Luu-The, V., Simard, J., Labrie, C., Bélanger, A., Labrie, F.: Intracrinology and hormone-dependent cancers, Epitheorese Klin. Farmakol. Farmakokinet. 11(1): 18-26 (1997) | |
| Publication Date | Accepted for publication: 15 April 1997 | |
| Full Text Language | English | |
| Order – Buy | pharmakonpress[at]pharmakonpress[.]gr | |
| Keywords | Cancer, hormone-dependent, intracrinology. | |
| Other Terms | review article | |
| Summary | Sex steroid hormones are produced by two main sources, the gonads and the peripheral tissues. Although the ovaries and testis are the exclusive sources of androgens and estrogens in small mammals, in higher primates and humans they are also produced in large amounts locally in the peripheral tissues via the adrenal precursors DHEA, its sulfate (DHEAS) and 4-androstenedione (4-dione), and could thus exert their action in the same cells that they are produced. A decade ago, our group has used the term intracrinology to describe this new mode of steroid hormone formation and action, which is specific to nuclear receptor-mediated action and represents an economical system that requires minimal amounts of hormone to exert maximal function. Such system also provides autonomous control to target tissues. The production of sex steroids in peripheral tissues via adrenal precursors is particularly important in postmenauposal women or elderly men in whom the ability of the ovaries and testis to produce estrogen and androgen, respectively, are dramatically decreased. Intracrinology is, thus, crucial for the breast and prostate cancers, the sex steroid-dependent diseases that appear more frequently in the advancing age. To better understand the role of intracrinology, in the last few years, our laboratory has focused in elucidating the pathway leading to the formation and degradation of sex steroid hormones in peripheral target tissues. We and others have demonstrated the existence of multiple genes encoding various steroidogenic enzymes, namely 3β-hydroxysteroid dehydrogenases (3β-HSD), 17β-hydroxysteroid dehydrogenases (17β-HSD), and 5α-reductases. These genes are expressed in a tissue-specific manner, and they are also differentially regulated. It is noteworthy that the mutation of only one form is responsible for the congenital disease. Since the hormones provided by the other isoenzymes are not sufficient to cover the need of a specific organ, the general concept that most of the sex hormones are provided by gonads and distributed to different tissues by systemic circulation need thus to be revised. Recently, we find that cytokines regulate markedly the 3β– and 17β-HSD gene expression. We have also shown that over production of steroidogenic enzymes modulate potently the receptor activity. The results thus strengthen the crucial role of intracrine hormones, especially in androgen- and estrogen-dependent diseases, such as the prostate and breast cancers, respectively. | |
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