Do steroid hormones function via multiple signaling pathways? (original) (raw)
Related papers
Rapid, Nongenomic Steroid Actions: A New Age?
Frontiers in Neuroendocrinology, 2000
In the traditional theory of steroid action, steroids bind to intracellular receptors and modulate nuclear transcription after translocation of steroid-receptor complexes into the nucleus. Due to similarities of molecular structure, specific receptors for steroids, vitamin D(3) derivatives, and thyroid hormone are considered to represent a superfamily of steroid receptors. While genomic steroid effects characterized by their delayed onset of action and their sensitivity to blockers of transcription and protein synthesis have been known for several decades, rapid actions of steroids have been more widely recognized and characterized in detail only recently. Rapid effects of steroids, thyroid hormones, and the steroid hormone metabolite of vitamin D(3), 1alpha, 25-dihydroxyvitamin D(3), on cellular signaling and function may be transmitted by specific membrane receptors. Binding sites in membranes have been characterized, exposing binding features compatible with an involvement in rapid steroid signaling. Characteristics of putative membrane receptors are completely distinct from intracellular steroid receptors, a fact which is further supported by the inability of classic steroid receptor antagonists to block nongenomic steroid actions. A putative progesterone membrane receptor has been cloned and functionally expressed with regard to progesterone binding. Development of drugs that specifically affect nongenomic action alone or even both modes of action may find applications in various, areas such as in the cardiovascular and central nervous systems and treatment of preterm labor, infertility, and electrolyte abnormalities.
Vitamin D: a steroid hormone with progesterone-like activity
European review for medical and pharmacological sciences, 2018
This review is aimed at demonstrating the progesterone-like activity exerted by the active form of vitamin D, or calcitriol (1,25(OH)2D). To achieve this outcome, we compared the effects in vivo and in vitro exerted by progesterone and vitamin D, with a special focus on the female reproductive system and pregnancy. This is a literature review of the most important articles published in English on vitamin D as a hormone, mainly found by MEDLINE. Furthermore, a section of our review contains some unpublished data, concerning the analysis in silico of the similarities between the steric structure of progesterone and calcitriol, based on the availability of the experimental structures of progesterone and vitamin D3 receptors in complex with their physiological ligands in the RCSB Protein Data Bank. Vitamin D was shown to exert many physiological activities during the very early stages of gestation in perfect synchrony with progesterone. Both the molecules mutually help and reinforce the...
Steroids: genomic and non-genomic actions (Atena Editora)
Steroids: genomic and non-genomic actions (Atena Editora), 2023
Steroid hormones are important maintainers of human body homeostasis, in addition to having important roles in the development and maturation of fetal organs and controlling male and female reproductive cycles. Human steroids are produced from a common precursor, cholesterol, in specialized endocrine cells such as the testes, ovaries, and adrenal glands. Testosterone, estrogen, cortisol and aldosterone are some examples of the best-known steroid hormones. The common mechanism of action of steroids is genomic, which occurs through the binding of these hormones with intracellular receptors, which are ligand-dependent transcription factors, affecting the cell's gene transcription. However, some rapid physiological effects cannot be explained by the traditional model of action, as changes in the gene transcription process take a certain time to take effect. Thus, the non-genomic effects of steroids are currently being studied, which include actions on the cell membrane, where they alter the opening of ion channels and their cardiovascular effects. The article in question also addresses the two-step action model of steroid hormones, focusing on reproductive hormones and vitamin D.
1,25-Dihydroxyvitamin D3 Regulates Estrogen Metabolism in Cultured Keratinocytes*
Endocrinology, 1997
Local estrogen metabolism may play an important role in modulating cell development in peripheral tissues such as breast, adipose, and bone. C 19 androgens are converted to C 18 estrogens by the enzyme aromatase, overexpression of which is associated with breast cancer. Interconversion of active estradiol (E 2) to inactive estrone is controlled by various isoforms of the enzyme 17-hydroxysteroid dehydrogenase (17HSD). We have studied the expression of these two enzymes in human keratinocytes and report rapid changes in 17HSD activity in response to treatment with 1,25-dihydroxyvitamin D 3 [1,25-(OH) 2 D 3 ]. Keratinocytes cultured in serum-free medium showed aromatase activity of 2.5 fmol/h⅐mg cell protein, which was unaffected by any culture treatment. A much higher level of 17HSD activity was observed in the keratinocytes, predominantly conversion of E 2 to estrone (ϳ120 pmol/h⅐mg cell protein). This inactivation of E 2 increased in a dose-dependent fashion after treatment of the cells with antiproliferative doses of 1,25-(OH) 2 D 3 (0.1-200 nM). The effect of 1,25-(OH) 2 D 3 on 17HSD activity was enhanced by simultaneous treatment with dexamethasone, which also increased the antiproliferative action of 1,25-(OH) 2 D 3. Reverse transcription-PCR and Northern analysis showed that keratinocytes expressed messenger RNA for three 17HSD isoenzymes (types I, II, and IV). Treatment with 1,25-(OH) 2 D 3 (10 nM for 20 h) resulted in the up-regulation of messenger RNA levels for type 2 17HSD. Further RNA studies combined with E 2 binding experiments demonstrated the presence of estrogen receptors in the cultured keratinocytes. These data indicate that keratinocytes are potential targets for systemically or locally produced estrogens, which may, in turn, play a key role in the development of normal skin. In particular, we propose that 17HSD isoenzymes are key target genes for 1,25-(OH) 2 D 3 in keratinocytes and may be an important feature of the antipsoriatic effects of vitamin D and its analogs.
Circulation, 2005
Background— 1,25(OH) 2 vitamin D 3 exerts multiple effects in human vascular smooth muscle cells (VSMCs). We therefore tested the possibility that VSMCs possess an endogenous 25-hydroxyvitamin D 3 -1α-hydroxylase system, the final enzyme in the biosynthetic pathway of 1,25(OH) 2 D 3 . Methods and Results— We assessed the expression and activity of 25-hydroxyvitamin D 3 -1α-hydroxylase by real-time polymerase chain reaction and the conversion of 25(OH)D 3 into 1,25(OH) 2 D 3 . First, 25-hydroxyvitamin D 3 -1α-hydroxylase mRNA was identified in cultured VSMCs by real-time polymerase chain reaction. Second, in cells treated daily (3 days) with parathyroid hormone (66 nmol/L), estradiol-17β (30 nmol/L), raloxifene (3 μmol/L), and the phytoestrogens genistein (3 μmol/L), biochainin A (3 μmol/L), and 6-carboxy biochainin A (30 nmol/L), 25-hydroxyvitamin D 3 -1α-hydroxylase mRNA increased by 43±13%, ( P <0.05) 7±24% ( P =NS), 176±28% ( P <0.01), 65±11% ( P <0.05), 152±24% ( P <...
Steroid Chemistry and Steroid Hormone Action
The first chapter includes an overview of steroid hormone structure, nomenclature, and action. This introductory chapter contains biochemical language we will need to understand the more physiological concepts in the later chapters.