Mechanism of steroid hormone action

overall Mechanism of steroid hormone action in endocrinolgy.

1. Presentation On Mechanism of Steroid Hormone Action Shashi Kant

2. Steroid Hormones Steroid Hormones are chemical messengers that transport signals from one cell to another. Are not packaged, but synthesized and immediately released . Are all derived from the same parent compound: c holesterol . Enzymes which produce steroid hormones from cholesterol are located in mitochondria and smooth ER . Steroids are lipid soluble and thus are freely permeable to membranes so are not stored in cells .

3. Steroid Hormones A re not water soluble so have to be carried in the blood complexed to specific binding globulins. Corticosteroid binding globulin carries cortisol . Sex steroid binding globulin carries testosterone and estradiol . In some cases a steroid is secreted by one cell and is converted to the active steroid by the target cell: ( androgen is secreted by the gonad and converted into estrogen in the brain ).

4. Steroid H ormones Steroid hormones play important roles in: - carbohydrate regulation (glucocorticoids) - mineral balance (mineralocorticoids) - reproductive functions (gonadal steroids) Steroids also play roles in inflammatory responses, stress responses, bone metabolism, cardiovascular fitness, behavior, cognition, and mood.

5. Steroids are lipophilic molecules. All steroids, except calcitriol , have cyclopentanoperhydrophenanthrene structure ( sterane ). Structure of Steroid Hormones The parental precursor of steroids - cholesterol

6. Itnracelluler receptor located inside target cell, in the cytoplasm or nucleus, and function as ligand dependent transcription factor. The HRC bind to promoter regions of responsive gene and stimulate or sometime inhibits transcription from those genes. The mechanism of action of steroid hormone is to modulate gene expression in target cells. By selectively affecting transcription from a battery of genes, the concentration of those respectively proteins are altered , which clearly can change the phenotype of the cell.

7. Structure of Intracellular Receptor Intracellular Receptor are composed of a single polypeptide chain that has, in the simplest analysis, three distinct domains: The amino-terminal : In most cases, this region is involve in activating or stimulating transcription by interacting with other components of the transcriptional machinery. The sequence is highly variable among different receptor. DNA binding domain: amino acid in this region are responsible for binding of the receptor to specific sequence of DNA. The carboxy-terminus or ligand-binding domain: this is the region that binds hormone.

8. Structure of Intracellular receptors Model of typical steroid hormone receptor Variable domain – interacts with other transcription factors DNA-binding domain – „zinc finger “ Hormone- binding domain 1 2 3 H 2 N- - COOH „zinc finger structure“

9. Hormone- receptor binding and interaction with DNA Steroid hormone enter the cell by simple diffusion across the plasma membrane the receptors exist either in the cytoplasm or nucleus, which is where they meet the hormone. when hormone bind to receptor, a characteristic series of events occurs: Receptor activation is the term used to describe conformational change in the receptor induced by hormone-binding. The major consequence of activation is that the receptor become competent to bind DNA. Activated receptor bind to “hormone response elements”. which are short specific sequence of DNA that are localized in promoter of hormone-responsive genes. In most cases, hormone-receptor complex bind DNA in pair. The hormone responsive elements are made-up of mostly inverted repeats or direct repeats or everted repeated at least three or 2-8 times respectively. Transcription from thus genes to which the receptor id bound is affected. Most commonly, receptor binding stimulates transcription. The hormone receptor complex thus function as a transcription factor.

10. Steroid Hormones: Molecular Action

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