The steroid hormones comprise a large and important family of cell regulators. These include sex hormones (estrogens, progestins, androgens), adrenal cortical hormones (glucocorticoids, mineralocorticoids), vitamin D, and insect hormones (ecdysteroids). As discussed in Sect. 3.1, these agents combine with intracellular receptor proteins, converting them to functional transcription factors, which then bind in the genome to influence the expression of specific genes. Thus, receptors for steroid hormones, as well as for thyroid hormones and retinoic acid, differ from the receptors described in previous chapters, which are located in the plasma membrane and utilize a signal transduction process (second messenger) to deliver the regulatory signal within the responsive cell.

Steroid Hormone Receptors

Publisher Summary This chapter discusses different aspects of steroid hormone receptors. Steroid hormones show different kinds of activities when examined at the physiological level. Differences may be also classified in terms of gross biological responses. Studies of the development of male secondary sex organs and hypothalamus in mammals, and of the oviduct in avians and batracians suggest that hormones such as estradiol or testosterone can promote the formation of morphologically and functionally stabilized new type of cells, enough to justify thinking in terms of differentiation processes. There are intracellular specific protein receptors for binding steroid hormones, all properties of which are compatible with the assumption that they are receptors. It is found that when estradiol, estrone, and estriol are compared, the rate of dissociation of uterine receptor steroid complexes is similar for the three steroids, but the rate of association is slower for the two lower affinity ones than for estradiol. The kinetic parameters of the binding reaction of the uterine receptor-estradiol are also studied.

Steroid hormone receptors

THE regulation of protein synthesis in the target tissue is undoubtedly the principal action of steroid hormones. The steroid molecule must be transported to the target tissue via the bloodstream and tissue fluids. It then penetrates the cell by simple or facilitated diffusion. On entry of the hormone into the cell, it is bound to a specific hormone receptor. This hormone-receptor complex is then transferred to the nucleus, in an "activated" form, where it is bound to the target-cell genome. Then, by a yet undefined process, the target cell responds by increased RNA synthesis followed by increased protein synthesis ( . . .

Mechanism of action of the sex steroid hormones (second of three parts).

I. A Contemporary Model for the Mechanism of Action of Androgens.- 1. Definitions.- 2. The Model for the Mechanism of Action of Androgens.- 3. Experimental Support for the Model.- a) Antiandrogens.- b) Experimental Testicular Feminisation Syndromes.- c) Specificity of Induction and Dose-Response Phenomena.- d) Temporal Integration of Steroid-Mediated Responses.- e) Tumours with Different Sensitivities to Androgens.- 4. Limitations of the Model of Androgen Action.- a) Fundamental Mechanisms of Hormone Action.- b) Redundant (Aberrant) Binding.- c) General Applicability of the Model.- d) Acute Tissue-Specificity of Androgenic Responses.- e) Androgen Responses Independent of the Receptor System.- f) Hormonal Synergism.- g) Responses Independent of Transcription.- 5. Conclusions.- II. The Metabolism of Androgens in Relation to Their Mechanism of Action.- 1. Relative Biological Activities of Testosterone and Its Metabolites.- 2. General Comments on the Metabolism of Androgens.- 3. Developmental Aspects of the Metabolism of Testosterone.- a) Foetal Development.- b) Neonatal Development.- c) Adult Development.- d) Fluctuations in the Circulating Concentrations of Androgens.- 4. Androgenic Responses Not Mediated by 5?-dihydrotestosterone.- 5. Interconversion of Steroid Hormones.- 6. Conclusions.- III. Initial Events in the Mechanism of Action of Androgens.- 1. The Uptake, Retention, and Release of Androgens: Studies on Rat Ventral Prostate Gland.- a) Transport of Testosterone and Related Steroids in Plasma.- b) Entry of Testosterone into Cells.- c) Cytoplasmic Receptors for Androgens.- d) Antiandrogens.- e) The Nuclear Binding of 5?-dihydrotestosterone.- f) Reconstituted, Cell-Free Systems for the Nuclear Transfer of 5?-dihydrotestosterone: the Acceptor Hypothesis.- g) The Structure of Chromatin and the Nature of Nuclear Acceptor Sites.- h) The Exit of 5?-dihydrotestosterone from the Prostate Gland: Receptor Cycling.- i) Binding of Steroids Other than 5?-dihydrotestosterone.- j) Purification of Receptor Proteins.- 2. The Binding of Androgens in Other Target Cells.- a) Distribution and Specificity of Receptors for Androgens and Related Steroids.- b) Physical Properties of Cytoplasmic and Nuclear Receptors.- c) Binding of Hormones Other than Androgens.- d) Specificity of Androgenic Responses.- 3. Initial Biochemical Events Stimulated by Androgens.- a) Protein Synthesis.- b) Activation of Protein Phosphokinases.- c) Stimulation of the Initiation Step of Protein Synthesis.- d) The Androgenic Regulation of RNA Synthesis: Receptor Effects in vitro.- 4. Conclusions.- IV.Early Events Stimulated by Androgens.- 1. Early Biochemical Changes Stimulated by Androgens.- 2. A More Detailed Enquiry into Enzyme Induction by Androgens: Aldolase in Rat Prostate.- 3. Experimental Models for Studying Tissue-Specific Responses.- a) Rat Seminal Vesicle.- b) Mouse Kidney.- 4. Morphologic Aspects of Androgenic Stimulation.- 5. Conclusions.- V.Late Events in the Mechanism of Action of Androgens.- 1. Cell Renewal and Morphologic Studies on the Mitogenic Activity of Testosterone and Its Metabolites.- 2. Biochemical Approaches to the Regulation of Mitosis in Rat Ventral Prostate Gland.- a) Enzymes Engaged in DNA Replication.- b) Proteins Regulating the Onset of Mitosis.- c) DNA-Unwinding Proteins.- d) Synthesis of Histones.- 3. Conclusions.- Overall Conclusions.- References.

The Mechanism of Action of Androgens

Publisher Summary This chapter discusses the cellular receptors and mechanisms of action of steroid hormones. The chapter covers those aspects related to the action of estrogens, androgens, progestins, glucocorticoids, and mineralocorticoids in vertebrates. The search for receptor proteins for these steroid hormones in most instances follows a unique pattern which includes (1) study of the uptake and retention of a radioactive hormone; (2) identification of the hormone presumed to be the active form; (3) detection and isolation of a specific protein that binds an active steroid but not an inactive steroid with a high affinity, and exists in larger amounts in target cells than in insensitive cells; and (4) demonstration that steroid antagonists can interfere with receptor binding of an active steroid. Studies on steroid receptors have been recently extended to several more biodynamic aspects such as qualitative and quantitative analysis of receptor proteins and their relation to biological responses of target cells and to some clinical situations. Concentrated efforts, however, are being made to discover the molecular mechanism whereby a steroid receptor complex may participate in the regulation of gene expression of the target cells. For this reason extensive studies have been carried out on the interaction of the steroid-receptor complex and the nuclear components of target cells. The chemical structures of many representative steroid hormones, natural or synthetic, and their antagonists are shown.

Samperez S

Papers

Testosterone "receptors" in purified nuclei of rat anterior hypophysis.

Binding and metabolism of (3H)-testosterone in the nuclei of rat pituitary in vivo.