what substance stimulates renal hydroxylation in the process of producing vitamin d course hero

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Do vitamin D hydroxylases respond to endocrine modulators?

The activity of 1 alpha OHase is known to be under the control of a series of endocrine modulators, particularly parathyroid hormone (PTH) and estrogens. We report here our studies in humans concerning the behaviour of vitamin D hydroxylases in some pathological conditions.

How is vitamin D synthesized in the body?

Vitamin D is considered to be devoid of direct biological activity. It must be first hydroxylated in the liver by a 25-hydroxylase (25OHase), then in the kidney by a 1 alpha-hydroxylase (1 alpha OHase) which is responsible for the synthesis of the active metabolite, 1,25-dihydroxyvitamin D (1,25 (OH)2D).

Does vitamin D have to be hydroxylated?

Vitamin D and its metabolites, 25OHD and 1,25(OH)2D, can also be hydroxylated in the 24 position. In the absence of 25-hydroxylation this may serve to activate the metabolite or analog as 1,25(OH)2D and 1,24(OH)2D have similar biologic potency.

How does vitamin D affect 25-hydroxylation?

In general, 25-hydroxylation in the liver is little affected by vitamin D status. However, CYP27A1 expression in the intestine (31) and kidney (32) is reduced by 1,25(OH)2D. Not surprisingly bile acids decrease CYP27A1 expression (33) as does insulin (34) through an unknown mechanism.

Which cells are responsible for controlling renal blood flow, glomerular filtration, and renin secretion?

What hormones are produced when the heart dilates?

What is tubular reabsorption?

What causes arteriolar vasoconstriction?

What happens when the bladder accumulates 250 to 300 ml of urine?

What is the functional unit of the kidney?

Which organ contains all the glomeruli and portions of the tubules of the kidneys?

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Which cells are responsible for controlling renal blood flow, glomerular filtration, and renin secretion?

Control of renal blood flow, glomerular filtration, and renin secretion occur at the JGA. Together, the juxtaglomerular cells and macula densa cells form the JGA. The control of renal blood flow, glomerular filtration, and renin secretion is not directed by any of the other options.

What hormones are produced when the heart dilates?

Natriuretic peptides inhibit renin and aldosterone during heart failure when the heart dilates. These make up a group of peptide hormones, including atrial natriuretic peptide (ANP), secreted from myocardial cells in the atria and brain natriuretic peptide (BNP) secreted from myocardial cells in the cardiac ventricles. When the heart dilates during volume expansion or heart failure, ANP and BNP inhibit sodium and water absorption by kidney tubules, inhibit the secretion of renin and aldosterone, vasodilate the afferent arterioles, and constrict the efferent arterioles. The result is increased urine formation, leading to decreased blood volume and blood pressure.

What is tubular reabsorption?

Tubular reabsorption is the movement of fluids and solutes from the tubular lumen to the peritubular capillary plasma. This selection is the only option that correctly identifies the process.

What causes arteriolar vasoconstriction?

The blood vessels of the kidney are innervated by the sympathetic noradrenergic fibers that cause arteriolar vasoconstriction and reduce renal blood flow. The other options are not involved in this process.

What happens when the bladder accumulates 250 to 300 ml of urine?

When the bladder accumulates 250 to 300 ml of urine, it contracts and the internal urethral sphincter relaxes through activation of the spinal reflex arc (known as the micturition reflex).

What is the functional unit of the kidney?

The nephron is the functional unit of the kidney. Although the other options are also located in the kidney, they are not its functional units.

Which organ contains all the glomeruli and portions of the tubules of the kidneys?

The cortex contains all the glomeruli and portions of the tubules of the kidneys. Although the other options are also located in the kidney, they do not contain the glomeruli.

Which hormone is the major regulator of the renal 1-hydroxylase?

3. Parathyroid hormone, FGF23, calcium and phosphate are the major regulators of the renal 1-hydroxylase; regulation of the extra renal 1-hydroxylase differs from that in the kidney and involves cytokines.

How does vitamin D transcription work?

Vitamin D-initiated gene transcription. 1,25(OH)2D enters the target cell and binds to its receptor, VDR. The VDR then heterodimerizes with the retinoid X receptor (RXR). This increases the affinity of the VDR/RXR complex for the vitamin D response element (VDRE), a specific sequence of nucleotides in the promoter region of the vitamin D responsive gene. Binding of the VDR/RXR complex to the VDRE attracts a complex of proteins termed coactivators to the VDR/RXR complex. The DRIP (Mediator) coactivator complex spans the gap between the VDRE and RNA polymerase II and other proteins in the initiation complex centered at or around the TATA box (or other transcription regulatory elements). SRC coactivators recruit histone acetyl transferases (HAT) to the gene promoting the opening up of its structure to enable the transcription machinery to work. Transcription of the gene is initiated to produce the corresponding mRNA, which leaves the nucleus to be translated to the corresponding protein.

Where is vitamin D3 produced?

Vitamin D3is produced in the skin from 7-dehydrocholesterol by UV irradiation, which breaks the B ring to form pre-D3. Pre-D3isomerizes to D3or with continued UV irradiation to tachysterol and lumisterol. D3is preferentially removed from the skin, bound to DBP. The liver and other tissues metabolize vitamin D, whether from the skin or oral ingestion, to 25OHD, the principal circulating form of vitamin D. Several enzymes have 25-hydroxylase activity, but CYP2R1 is the most important. 25OHD is then further metabolized to 1,25(OH)2D principally in the kidney, by the enzyme CYP27B1, although other tissues including various epithelial cells, cells of the immune system, and the parathyroid gland contain this enzymatic activity. 1,25(OH)2D is the principal hormonal form of vitamin D, responsible for most of its biologic actions. The production of 1,25(OH)2D in the kidney is tightly controlled, being stimulated by parathyroid hormone, and inhibited by calcium, phosphate and FGF23. Extrarenal production of 1,25(OH)2D as in keratinocytes and macrophages is under different control, being stimulated primarily by cytokines such as tumor necrosis factor alfa (TNFa) and interferon gamma (IFNg). 1,25(OH)2D reduces 1,25(OH)2D levels in cells primarily by stimulating its catabolism through the induction of CYP24A1, the 24-hydroxylase. 25OHD and 1,25(OH)2D are hydroxylated in the 24 position by this enzyme to form 24,25(OH)2D and 1,24,25(OH)3D, respectively. This 24-hydroxylation is generally the first step in the catabolism of these active metabolites to the final end product of calcitroic acid, although 24,25(OH)2D and 1,24,25(OH)3D have their own biologic activities. CYP24A1 also has 23-hydroxylase activity that leads to a different end product. Different species differ in their ratio of 23-hydroxylase/24-hydroxyase activity in their CYP24A1 enzyme, but in humans the 24-hydroxyase activity predominates. CYP24A1 is induced by 1,25(OH)2D, which serves as an important feedback mechanism to avoid vitamin D toxicity. In macrophages, CYP24A1 is either missing or defective, so in situations such as granulomatous diseases like sarcoidosis in which macrophage production of 1,25(OH)2D is increased, hypercalcemia and hypercalciuria due to elevated 1,25(OH)2D can occur.

What is the role of 1,25(OH)2D in gene transcription?

VDR is a transcription factor that partners with other transcription factors such as retinoid X receptor that when bound to 1,25(OH)2D regulates gene transcription either positively or negatively depending on other cofactors to which it binds.

What is the role of 1,25(OH)2D in calcium homeostasis?

The classic target tissues—bone, gut, and kidney—are involved with calcium homeostasis. The mechanisms by which 1,25(OH)2D regulates transcellular calcium transport are best understood in the intestine.

Where are vitamin D metabolites transported?

The vitamin D metabolites are transported in blood bound to DBP and albumin. Very little circulates as the free form. The liver produces DBP and albumin, production that is decreased in liver disease, and these proteins may be lost in protein losing enteropathies or the nephrotic syndrome. Thus individuals with liver, intestinal or renal diseases which result in low levels of these transport proteins may have low total levels of the vitamin D metabolites without necessarily being vitamin D deficient as their free concentrations may be normal.

Which enzyme catabolizes 25(OH)D and 1,25(OH)2D?

The major enzyme that catabolizes 25(OH)D and 1,25(OH)2D is the 24-hydroxylase; like the 1-hydroxylase it is tightly controlled in the kidney in a manner opposite to that of the 1-hydroxylase, but like the 1-hydroxylase it is widespread in other tissues where its regulation is different from that of the kidney. 5.

Which cells are responsible for controlling renal blood flow, glomerular filtration, and renin secretion?

Control of renal blood flow, glomerular filtration, and renin secretion occur at the JGA. Together, the juxtaglomerular cells and macula densa cells form the JGA. The control of renal blood flow, glomerular filtration, and renin secretion is not directed by any of the other options.

What hormones are produced when the heart dilates?

Natriuretic peptides inhibit renin and aldosterone during heart failure when the heart dilates. These make up a group of peptide hormones, including atrial natriuretic peptide (ANP), secreted from myocardial cells in the atria and brain natriuretic peptide (BNP) secreted from myocardial cells in the cardiac ventricles. When the heart dilates during volume expansion or heart failure, ANP and BNP inhibit sodium and water absorption by kidney tubules, inhibit the secretion of renin and aldosterone, vasodilate the afferent arterioles, and constrict the efferent arterioles. The result is increased urine formation, leading to decreased blood volume and blood pressure.

What is tubular reabsorption?

Tubular reabsorption is the movement of fluids and solutes from the tubular lumen to the peritubular capillary plasma. This selection is the only option that correctly identifies the process.

What causes arteriolar vasoconstriction?

The blood vessels of the kidney are innervated by the sympathetic noradrenergic fibers that cause arteriolar vasoconstriction and reduce renal blood flow. The other options are not involved in this process.

What happens when the bladder accumulates 250 to 300 ml of urine?

When the bladder accumulates 250 to 300 ml of urine, it contracts and the internal urethral sphincter relaxes through activation of the spinal reflex arc (known as the micturition reflex).

What is the functional unit of the kidney?

The nephron is the functional unit of the kidney. Although the other options are also located in the kidney, they are not its functional units.

Which organ contains all the glomeruli and portions of the tubules of the kidneys?

The cortex contains all the glomeruli and portions of the tubules of the kidneys. Although the other options are also located in the kidney, they do not contain the glomeruli.