Pharmacology of adrenal corticosteroids Flashcards
Briefly describe the synthesis of adrenal steroid hormones and the factors which control it
Cholesterol is converted to pregnenolone by the enzyme cholesterol side-chain cleavage enzyme (CYP11A1) in the adrenal cortex.
Pregnenolone is then converted to other steroid hormones, including cortisol, aldosterone, and androgens, through a series of enzymatic reactions.
The synthesis of adrenal steroid hormones is regulated by the hypothalamic-pituitary-adrenal (HPA) axis. The hypothalamus secretes corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH) into the bloodstream.
ACTH then stimulates the adrenal cortex to synthesize and release cortisol.
Cortisol exerts negative feedback on the HPA axis, inhibiting the secretion of CRH and ACTH. This feedback loop helps to maintain the appropriate levels of cortisol in the body.
The synthesis of aldosterone is regulated by the renin-angiotensin-aldosterone system (RAAS). This system is activated in response to low blood pressure or low blood volume.
Renin, an enzyme produced by the kidneys, converts angiotensinogen to angiotensin I, which is then converted to angiotensin II by the enzyme angiotensin-converting enzyme (ACE).
Angiotensin II stimulates the adrenal cortex to synthesize and release aldosterone, which helps to increase blood volume and blood pressure.
Overall, the synthesis of adrenal steroid hormones is tightly regulated by a complex system of hormonal feedback loops involving the HPA axis and the RAAS.
Outline the process involved in the release and plasma transport of adrenal steroid hormones
Stimulation: Adrenal steroid hormone release is regulated by a complex system of signals involving the hypothalamus, pituitary gland, and adrenal glands. In response to stress or other stimuli, the hypothalamus secretes corticotropin-releasing hormone (CRH), which signals the pituitary gland to release adrenocorticotropic hormone (ACTH).
Synthesis: ACTH then travels through the bloodstream to the adrenal glands, where it binds to receptors on the outer layer of the gland, called the adrenal cortex. This triggers the synthesis and release of adrenal steroid hormones, including cortisol (a glucocorticoid) and aldosterone (a mineralocorticoid).
Plasma transport: Once released, adrenal steroid hormones bind to transport proteins in the bloodstream, which help to protect the hormones from degradation and control their distribution throughout the body. The transport proteins for cortisol include cortisol-binding globulin (CBG) and albumin, while aldosterone is primarily transported by a protein called corticosteroid-binding globulin (CBG).
Tissue uptake: Adrenal steroid hormones are taken up by target tissues throughout the body, where they bind to specific receptors and exert their effects. For example, cortisol binds to receptors in cells involved in glucose metabolism, immune function, and stress response, while aldosterone binds to receptors in the kidney and other tissues involved in electrolyte balance.
Feedback regulation: Adrenal steroid hormone production is regulated by a negative feedback system, where elevated levels of cortisol and aldosterone in the bloodstream signal the hypothalamus and pituitary gland to reduce the production of CRH and ACTH, respectively. This helps to maintain normal hormone levels and prevent overproduction of adrenal steroid hormones.
Outline the physiological actions of the adrenal steroid hormones
Glucocorticoids, such as cortisol, have a wide range of physiological actions, including:
Regulation of metabolism: Cortisol helps to regulate glucose metabolism by increasing the breakdown of glycogen into glucose and promoting gluconeogenesis (the production of glucose from non-carbohydrate sources such as amino acids). Cortisol also increases the breakdown of fats into fatty acids, which can be used as an energy source.
Immune function: Cortisol has anti-inflammatory and immunosuppressive effects, which can help to reduce inflammation and limit the immune response. This can be beneficial in the short term, but chronic exposure to high levels of cortisol can impair immune function and increase the risk of infections.
Stress response: Cortisol is often referred to as the “stress hormone” because it is released in response to stress and helps the body to cope with stressors. Cortisol can increase heart rate and blood pressure, and mobilize energy stores to provide the body with the energy it needs to respond to the stressor.
Mineralocorticoids, such as aldosterone, have a more specific role in regulating electrolyte balance and blood pressure. The physiological actions of mineralocorticoids include:
Sodium and potassium balance: Aldosterone promotes the reabsorption of sodium ions and the excretion of potassium ions in the kidney, which helps to maintain normal electrolyte balance.
Water balance: Because sodium is the main electrolyte in the extracellular fluid, aldosterone also indirectly regulates water balance by controlling sodium reabsorption. By increasing the reabsorption of sodium, aldosterone increases the osmotic pressure of the extracellular fluid, which leads to water reabsorption and an increase in blood volume.
Blood pressure regulation: The increase in blood volume and sodium reabsorption caused by aldosterone also leads to an increase in blood pressure, making it an important hormone in the regulation of blood pressure.
Discuss the physiological basis for the symptoms in Cushing’s disease and Addison’s disease
Cushing’s disease is caused by a benign tumor in the pituitary gland that produces excessive amounts of adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce cortisol. The excess cortisol in the body can cause a variety of symptoms, including:
Weight gain, especially around the face, neck, and abdomen
Thinning skin that bruises easily
Acne or other skin problems
Muscle weakness and wasting
High blood pressure
Diabetes or high blood sugar
Mood changes, such as anxiety and depression
Irregular menstrual periods in women
The physiological basis for these symptoms is that cortisol is a hormone that regulates a variety of physiological processes, including metabolism, immune function, and stress response. Excess cortisol can interfere with these processes and lead to the symptoms described above.
Addison’s disease, on the other hand, is caused by a deficiency in cortisol production due to damage to the adrenal glands. The symptoms of Addison’s disease are the opposite of those seen in Cushing’s disease, and include:
Weight loss and decreased appetite
Fatigue and weakness
Low blood pressure
Darkening of the skin
Nausea and vomiting
Salt cravings
Muscle and joint pain
Depression and anxiety
