Progesterone in uterus and plasma. I. Binding in rat uterus 105,000 g supernatant.
TL;DR: The specific binding site concentration per uterus shows very marked variations with the endocrine status of the rat.
Abstract: In the rat uterus 105,000 g supernatant, progesterone is bound by a specific (high affinity, low capacity) component and also by nonspecific (low affinity, high capacity) component (s). The specific component has many features identical with those of plasma corticosteroid binding globulin (sedimentation coefficient, electrophoretic mobility on paper and polyacrylamide gel, chromatographic behavior through Sephadex G-200, thermolability, steroid specificity, association constant at 4 C and antigenicity). The specific binding site concentration per mg of protein in uterus supernatant is 70 % that of plasma in estradiol-primed castrated rat s, whereas it is very low in kidney or diaphragm supernatant. The specific binding site concentration per uterus shows very marked variations with the endocrine status of the rat. It is very low in prepuberal rats, 12 times higher in recently castrated adult rats, 30 times higher in estradiolprimed castrated rats and 100 times higher in normal adult rats (random as far as...
Citations
More filters
TL;DR: Progesterone effects on proliferation and decidualization in the uterus during the menstrual cycle, and effects on lactation and Bone VIII.
Abstract: I. Introduction II. Synthesis and Secretion of Progesterone III. The Progesterone Receptor A. PR expression and regulation IV. Progesterone Regulation of Gene Expression in the Uterus, Ovary, and Chick Oviduct A. Progesterone effects on proliferation and decidualization in the uterus during the menstrual cycle B. Progesterone regulation of insulin-like growth factor (IGF) pathways in the endometrium C. Control of ovulation D. Implantation, uterine proliferation, and early pregnancy E. Myometrial contractility F. Chick oviduct V. Progesterone Action in the Breast A. Effect of progesterone on proliferation of the normal breast B. Progesterone regulation of genes associated with cell cycle progression C. Progesterone regulation of growth factors and growth factor receptors in the breast D. Markers of progestin action in the breast E. Progesterone effects on lactation VI. Progesterone Effects in the Brain VII. Progesterone Effects on Bone VIII. Antiestrogen Action of Progesterone A. Inhibition of ER expressio...
962 citations
TL;DR: The data discussed herein demonstrate the great variation in target-tissue response that can occur after administration of steroid hormones, and direct quantitative evidence that sex steroids cause a net increase in the intracellular amounts of specific mRNA molecules in target tissues is provided.
Abstract: The data discussed herein demonstrate the great variation in target-tissue response that can occur after administration of steroid hormones. The female sex steroids can exert regulatory effects on the synthesis, activity, and possibly even the degradation of tissue enzymes and structural proteins. Each response, nevertheless, appears to be dependent on the synthesis of nuclear RNA. In many instances, the steroid actually promotes a qualitative change in the base composition and sequence of the RNA synthesized by the target cell, implying a specific effect on gene transcription. Most important is our direct quantitative evidence that sex steroids cause a net increase in the intracellular amounts of specific mRNA molecules in target tissues. It thus appears that we are discovering a pattern of steroid hormone action which includes (Fig. 1): (i) uptake of the hormone by the target cell and binding to a specific cytoplasmic receptor protein; (ii) transport of the steroid-receptor complex to the nucleus; (iii) binding of this "active" complex to specific "acceptor" sites on the genome (chromatin DNA and acidic protein); (iv) activation of the transcriptional apparatus resulting in the appearance of new RNA species which includes specific mRNA's; (v) transport of the hormone-induced RNA to the cytoplasm resulting in synthesis of new proteins on cytoplasmic ribosomes; and (vi) the occurrence of the specific steroid-mediated "functional response" characteristic of that particular target tissue. To elucidate fully the mechanism of steroid hormone action we must study the biochemistry of the process by which information held by the steroid hormone-receptor complex is transferred to the nuclear transcription apparatus. If our assumptions are correct, we should ultimately be able to discover how this hormone-receptor complex exerts a specific regulatory effect on nuclear RNA metabolism. Such regulation might be achieved (i) by direct effects on chromatin template leading to increased gene transcription and thus RNA synthesis; (ii) by activation of the polymerase complex itself; (iii) by inhibition of RNA breakdown; or (iv) by intranuclear processing of large precursor molecules so that smaller biologically active sequences are produced, and (v) by transport of RNA from the nucleus to the cytoplasmic sites of cellular protein synthesis.
866 citations
TL;DR: This chapter discusses the serum transport of steroid hormones, where the steroid-receptor complex apparently moves into the nucleus where it modifies the chromatin transcriptional activity which results in altered levels of protein synthesis.
Abstract: Publisher Summary This chapter discusses the serum transport of steroid hormones Steroid hormones are extensively bound to plasma proteins including albumin, corticosteroid binding globulin (CBG), and sex hormone binding globulin (SHBG) Because of its high concentration, albumin binding is important in determining the magnitude of the nonprotein bound or free fraction of a steroid in plasma The generally accepted model of steroid hormone action suggests that free steroid (in equilibrium with circulating binding proteins) diffuses passively through target cell membranes and binds to a soluble intracellular receptor The steroid-receptor complex apparently moves into the nucleus where it modifies the chromatin transcriptional activity which results in, among other things, altered levels of protein synthesis CBG has been differentiated from the intracellular glucocorticoid and progesterone receptors by its inability to bind synthetic glucocorticoids and progestins
766 citations
TL;DR: Literature on the hormonal control of ovoimplantation is reviewed and the recognition of ovarian hormones by endometrial cells and cell transcriptional events, and the mechanisms of the repression and activation of the blastocyst are reviewed.
Abstract: Publisher Summary This chapter discusses the hormonal control of ovoimplantation. The mammalian ovum undergoes several “trials” after its release from the ovarian follicule. The ovum must be fertilized as soon as possible after release otherwise it will degenerate within a few hours. It must then migrate or be transported through the oviduct within a definite interval, for if it arrives either too early or too late into the uterus it will encounter a hostile (toxic) environment. During the period of oviduct transit, the ovum must cleave and reach the morula stage of differentiation before it can coparticipate with the uterus in the initiation of implantation. Tubal or oviduct transit in most mammalian species occupies the first three–four days postfertilization. The interval between the arrival of the fertilized ovum into the uterus and the moment of its implantation is quite variable and depends on the species and on the physiological state of the female. The models of phases and states of uterine receptivity are also described in the chapter.
448 citations
01 Jan 1991
TL;DR: The dependence of human cancers on hormones, the detection and characterization of steroid receptor interactions, and the physiological and pharmacological implications of steroid hormone receptors are discussed.
Abstract: 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.
352 citations