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Corticoid Proteins

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Corticoid Proteins

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Corticoid Proteins Background

Corticoid, also called adrenocortical hormone,are hormones produced by the adrenal cortex, the outer region of the adrenal gland. These polycyclic steroid hormones have a range of roles that are important for the body’s response to stress (for example, the fight-or-flight response), and they can additionally regulate different functions in the body. Changes to homeostasis, such as injury, chemical imbalances, infection, or psychological stress, will initiate a stress response. Examples of adrenocortical hormones that are involved in the stress response are aldosterone and cortisol. These hormones additionally regulating the conservation of water by the kidneys and glucose metabolism, respectively.

Classification

Adrenocortical hormones have three categories divided by function: mineralocorticoids, glucocorticoids, and androgens. Mineralocorticoid hormones are synthesized within the outer outermost layer of the adrenal cortex referred to as the zona glomerulosa. Their function is to regulate the concentration of electrolytes circulating in the blood. For instance, aldosterone functions to raise blood sodium levels and lower blood potassium levels by targeting the kidneys. Specifically, it binds receptors of cells that comprise the distal tubules of the kidneys which then stimulate ion channels to conserve sodium and excrete potassium. In additions, the ion gradient initiates conservation of water. The glucocorticoid family of hormones is synthesized in the middle layer of the adrenal cortex referred to as the zona fasciculata. These hormones regulate the process of proteins, fats, and carbohydrates by the human body. In additions, they can function in maintaining a normal stress response cycle.

Androgens, or sex hormones, are synthesized within the innermost layer of the adrenal cortex known as the zona reticularis. These hormones, like estrogen in females and testosterone in males, are commonly well-known for promoting sexual characteristics and therefore the maturation of reproductive organs of the respective gender.

Structure

Adrenocortical hormones are thought of steroid hormones because of the shared characteristic of a cholesterol backbone. The structures of various steroids differ by the kinds and locations of extra atoms on a cholesterol backbone. The cholesterol backbone consists of four hydrocarbon rings, three cyclohexane rings and one cyclopentane, that contribute to its insolubility in liquid environments. However, the hydrophobic nature allows them to readily diffuse through the plasma membrane of cells. This is important to the function of steroid hormones as they rely on cellular response pathways to restore the homeostatic imbalance that initiated the hormone release.

Synthesis

The synthesis of adrenocortical steroid hormones involves a sequence of oxidation-reduction reactions catalyzed by various of enzymes. Synthesis begins with a molecule of cholesterol. Through shared intermediates and pathways branching off those shared intermediates, the various categories of steroids are synthesized. Steroids are synthesized from cholesterol in their specific regions of the adrenal cortex. This process is controlled by steroidogenic acute regulative protein (StAR) which sits in the mitochondrial membrane and regulates the passage of cholesterol. This is the rate-limiting step of steroid biosynthesis. Once StAR has transported cholesterol into the mitochondria, the cholesterol molecule undergoes a string of oxidation-reduction reactions catalyzed by a series of enzymes from the family of cytochrome P450 enzymes. A coenzyme system referred to as adrenodoxin reductase transfers electrons to the P450 enzyme that initiates the oxidation-reduction reactions that transform cholesterol into the steroid hormones. Although synthesis begins within the mitochondria, the precursor is shuttled into the endoplasmic reticulum for treatment by enzymes present in the endoplasmic reticulum. The precursor is shuttled back to the mitochondria of the adrenal cortex where synthesis begins initially and synthesis is complete there.

References:

1. Dorina K.; et al. Unbinding of retinoic acid from its receptor studied by steered molecular dynamics. Biophysical Journal. 1999,76:188-197.

2. Dorina K.; et al. Binding of the estrogen receptor to DNA: The role of waters. Biophysical Journal. 1999,73: 557-570.

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