Nuclear receptor signaling — MCQs

10 questions

A 21-year-old woman presents with irregular menses, acne, and increased body hair growth. She says her average menstrual cycle lasts 36 days and states that she has heavy menstrual bleeding. She had her menarche at the age of 13 years. Her blood pressure is 125/80 mm Hg, heart rate is 79/min, respiratory rate is 14/min, and temperature is 36.7°C (98.1°F). Her body weight is 101.0 kg (222.7 lb) and height is 170 cm (5 ft 7 in). Physical examination shows papular acne on her forehead and cheeks. There are dark hairs present on her upper lip, periareolar region, linea alba, and hips, as well as darkening of the skin on the axilla and posterior neck. Which of the following endocrine abnormalities would also most likely be found in this patient?

A 55-year-old man comes to the physician with a 3-month history of headache, periodic loss of vision, and easy bruising. Physical examination shows splenomegaly. His hemoglobin concentration is 13.8 g/dL, leukocyte count is 8000/mm3, and platelet count is 995,000/mm3. Bone marrow biopsy shows markedly increased megakaryocytes with hyperlobulated nuclei. Genetic analysis shows upregulation of the JAK-STAT genes. The pathway encoded by these genes is also physiologically responsible for signal transmission of which of the following hormones?

A group of researchers is studying molecules and DNA segments that are critical for important cellular processes in eukaryotic cells. They have identified a region that is located about 28 bases upstream of the 5’ coding region. This region promotes the initiation of transcription by binding with transcription factors. Which of the following regions have these researchers most likely identified?

Researchers are experimenting with hormone levels in mice in fasting and fed states. To test hormone levels in the fed state, the mice are given an oral glucose load and various hormones are measured in a blood sample. Researchers are most interested in the hormone whose blood levels track evenly with C-peptide levels. The hormone the researchers are most interested in is responsible for which of the following actions in the body?

An investigator is studying the mechanism regulating pigment production in the skin. She has isolated a hormone produced by the anterior and intermediate lobe of the pituitary gland that stimulates neural crest-derived cells to produce pigments through the oxidation and polymerization of the amino acid tyrosine. This hormone is most likely cosecreted with a substance that acts on which of the following receptors?

A 65-year-old woman arrives for her annual physical. She has no specific complaints. She has seasonal allergies and takes loratadine. She had a cholecystectomy 15 years ago. Her last menstrual period was 9 years ago. Both her mother and her maternal aunt had breast cancer. A physical examination is unremarkable. The patient is given the pneumococcal conjugate vaccine and the shingles vaccine. A dual-energy x-ray absorptiometry (DEXA) scan is obtained. Her T-score is -2.6. She is prescribed a new medication. The next month the patient returns to her primary care physician complaining of hot flashes. Which of the following is the most likely medication the patient was prescribed?

A researcher is studying receptors that respond to epinephrine in the body and discovers a particular subset that is expressed in presynaptic adrenergic nerve terminals. She discovers that upon activation, these receptors will lead to decreased sympathetic nervous system activity. She then studies the intracellular second messenger changes that occur when this receptor is activated. She records these changes and begins searching for analogous receptor pathways. Which of the following receptors would cause the most similar set of intracellular second messenger changes?

A 16-year-old female presents to your clinic concerned that she has not had her menstrual cycle in 5 months. She has not been sexually active and her urine pregnancy test is negative. She states that she has been extremely stressed as she is in the middle of her gymnastics season and trying to get recruited for a college scholarship. Physical exam is remarkable for a BMI of 16, dorsal hand calluses, and fine hair over her cheeks. What other finding is likely in this patient?

A 66-year-old man comes to the physician because of a 3-month history of constipation and streaks of blood in his stool. He has had a 10-kg (22-lb) weight loss during this period. Colonoscopy shows an exophytic tumor in the sigmoid colon. A CT scan of the abdomen shows liver metastases and enlarged mesenteric and para-aortic lymph nodes. A diagnosis of stage IV colorectal cancer is made, and palliative chemotherapy is initiated. The chemotherapy regimen includes a monoclonal antibody that inhibits tumor growth by preventing ligand binding to a protein directly responsible for epithelial cell proliferation and organogenesis. Which of the following proteins is most likely inhibited by this drug?

Q10

An investigator is studying vitamin D metabolism in mice. He induces a gene mutation that interferes with the function of an enzyme in the renal proximal tubules that is required for vitamin D activation. He then measures serum levels of various metabolites. Production of which of the following will be impaired in this mouse?

Nuclear receptor signaling US Medical PG Practice Questions and MCQs

Question 1: A 21-year-old woman presents with irregular menses, acne, and increased body hair growth. She says her average menstrual cycle lasts 36 days and states that she has heavy menstrual bleeding. She had her menarche at the age of 13 years. Her blood pressure is 125/80 mm Hg, heart rate is 79/min, respiratory rate is 14/min, and temperature is 36.7°C (98.1°F). Her body weight is 101.0 kg (222.7 lb) and height is 170 cm (5 ft 7 in). Physical examination shows papular acne on her forehead and cheeks. There are dark hairs present on her upper lip, periareolar region, linea alba, and hips, as well as darkening of the skin on the axilla and posterior neck. Which of the following endocrine abnormalities would also most likely be found in this patient?

A. Aldosterone hyperproduction
B. Adrenaline hypersecretion
C. Hypothyroidism
D. Insulin resistance (Correct Answer)
E. Hypoestrogenism

Explanation: ***Insulin resistance*** - The patient exhibits several features suggestive of **Polycystic Ovary Syndrome (PCOS)**, including **irregular menses (oligomenorrhea)**, **acne**, **hirsutism** (increased body hair), and **obesity** (BMI 34.9 kg/m2). - Insulin resistance is a central pathophysiological feature of PCOS, leading to **hyperinsulinemia** which stimulates ovarian androgen production, exacerbating symptoms like hirsutism and acne. *Aldosterone hyperproduction* - **Aldosterone hyperproduction**, as seen in primary hyperaldosteronism, primarily causes **hypertension** and **hypokalemia**, none of which are explicitly indicated in this patient's presentation. - The patient's blood pressure is within a normal range, and there are no symptoms or signs pointing to electrolyte imbalances. *Adrenaline hypersecretion* - **Adrenaline hypersecretion** (e.g., in pheochromocytoma) typically presents with paroxysmal **hypertension**, **tachycardia**, palpitations, and anxiety. - These signs are absent in the patient, whose vital signs are stable and blood pressure is normal. *Hypothyroidism* - **Hypothyroidism** can cause irregular menses and weight gain, but it is typically associated with **cold intolerance**, fatigue, and dry skin, not acne or hirsutism. - The patient's presentation of androgen excess (acne, hirsutism) is inconsistent with hypothyroidism. *Hypoestrogenism* - **Hypoestrogenism** would typically present with symptoms such as **hot flashes**, vaginal dryness, and bone loss, and it would usually lead to oligomenorrhea or amenorrhea. - In PCOS, while estrogen levels can be dynamic, the primary issue is **androgen excess**, and estrogen levels are often normal or even elevated due to peripheral conversion of androgens.

Question 2: A 55-year-old man comes to the physician with a 3-month history of headache, periodic loss of vision, and easy bruising. Physical examination shows splenomegaly. His hemoglobin concentration is 13.8 g/dL, leukocyte count is 8000/mm3, and platelet count is 995,000/mm3. Bone marrow biopsy shows markedly increased megakaryocytes with hyperlobulated nuclei. Genetic analysis shows upregulation of the JAK-STAT genes. The pathway encoded by these genes is also physiologically responsible for signal transmission of which of the following hormones?

A. Oxytocin
B. Adrenocorticotropic hormone
C. Prolactin (Correct Answer)
D. Cortisol
E. Insulin

Explanation: ***Prolactin*** - Prolactin utilizes the **JAK-STAT signaling pathway** to exert its effects on target cells, particularly in the mammary glands. - The **JAK-STAT pathway** is crucial for cell growth, differentiation, and immune response, and its dysregulation is linked to myeloproliferative disorders like those involving megakaryocyte proliferation. *Oxytocin* - Oxytocin primarily acts through **G-protein coupled receptors** that activate the phospholipase C/inositol triphosphate pathway, not the JAK-STAT pathway. - Its main roles involve uterine contraction and milk ejection, which are distinct from the cellular proliferation regulated by JAK-STAT. *Adrenocorticotropic hormone* - ACTH binds to **G-protein coupled receptors** in the adrenal cortex, stimulating adenylyl cyclase and increasing cAMP levels. - This mechanism of action is distinct from the tyrosine kinase activity characteristic of the JAK-STAT pathway. *Cortisol* - Cortisol, a steroid hormone, primarily acts via **intracellular glucocorticoid receptors** that translocate to the nucleus to regulate gene transcription. - Its signaling mechanism involves direct gene regulation rather than a membrane-bound receptor-kinase cascade like JAK-STAT. *Insulin* - Insulin signals through a **receptor tyrosine kinase**, which, upon binding, autophosphorylates and initiates a cascade involving IRS proteins and the PI3K/Akt and MAPK pathways. - While it involves tyrosine phosphorylation, it is distinct from the JAK-STAT pathway, which is primarily activated by cytokine and growth hormone type I receptors.

Question 3: A group of researchers is studying molecules and DNA segments that are critical for important cellular processes in eukaryotic cells. They have identified a region that is located about 28 bases upstream of the 5’ coding region. This region promotes the initiation of transcription by binding with transcription factors. Which of the following regions have these researchers most likely identified?

A. TATA Box (Correct Answer)
B. RNA polymerase II
C. Small nuclear ribonucleoprotein (SnRNPs)
D. DNA methyltransferase
E. CAAT Box

Explanation: ***TATA Box*** - The **TATA box** is a core promoter element found in eukaryotic genes, typically located **25-35 base pairs upstream** of the transcription start site. - It plays a crucial role in initiating transcription by serving as a binding site for **transcription factors**, which in turn recruit **RNA polymerase II**. *RNA polymerase II* - **RNA polymerase II** is the enzyme responsible for transcribing protein-coding genes into mRNA. - While essential for transcription, it is an enzyme that binds to the promoter region (which includes the TATA box), rather than a regulatory DNA sequence itself. *Small nuclear ribonucleoprotein (SnRNPs)* - **SnRNPs** are components of the spliceosome, involved in the **splicing of pre-mRNA** to remove introns. - They are involved in post-transcriptional modification, not in the initiation of transcription. *DNA methyltransferase* - **DNA methyltransferase** is an enzyme involved in **DNA methylation**, a process that typically represses gene expression. - This enzyme modifies DNA, but it is not a DNA region that promotes transcription initiation. *CAAT Box* - The **CAAT box** is another common promoter element in eukaryotes, usually located further **upstream (70-80 base pairs)** from the transcription start site. - While it also binds transcription factors and influences transcription initiation, its location is generally *more distant* than the 28 bases upstream described, making the TATA box a more accurate fit for the given distance.

Question 4: Researchers are experimenting with hormone levels in mice in fasting and fed states. To test hormone levels in the fed state, the mice are given an oral glucose load and various hormones are measured in a blood sample. Researchers are most interested in the hormone whose blood levels track evenly with C-peptide levels. The hormone the researchers are most interested in is responsible for which of the following actions in the body?

A. Protein catabolism
B. Fatty acid breakdown
C. Fatty acid synthesis (Correct Answer)
D. Ketogenesis
E. Lipolysis

Explanation: ***Fatty acid synthesis*** - The hormone whose blood levels track evenly with **C-peptide** levels after a glucose load is **insulin**. - Insulin is a key anabolic hormone that promotes **fatty acid synthesis** from excess glucose in the fed state, particularly in the liver and adipose tissue. *Protein catabolism* - **Insulin** is an anabolic hormone that generally **inhibits protein catabolism** and promotes protein synthesis. - Conditions like **glucagon excess** or **cortisol excess** promote protein catabolism, not insulin. *Fatty acid breakdown* - **Insulin inhibits fatty acid breakdown** (beta-oxidation) by suppressing hormone-sensitive lipase. - **Glucagon** and **epinephrine** promote fatty acid breakdown, especially during fasting. *Ketogenesis* - **Insulin inhibits ketogenesis** by reducing the supply of fatty acids to the liver and inhibiting the enzymes involved in ketone body formation. - **Glucagon** and **low insulin levels** (as in uncontrolled diabetes or prolonged fasting) promote ketogenesis. *Lipolysis* - **Insulin is a potent inhibitor of lipolysis** (breakdown of triglycerides into fatty acids and glycerol) in adipose tissue. - **Glucagon**, **catecholamines**, and **growth hormone** stimulate lipolysis.

Question 5: An investigator is studying the mechanism regulating pigment production in the skin. She has isolated a hormone produced by the anterior and intermediate lobe of the pituitary gland that stimulates neural crest-derived cells to produce pigments through the oxidation and polymerization of the amino acid tyrosine. This hormone is most likely cosecreted with a substance that acts on which of the following receptors?

A. TSH receptor
B. Glucocorticoid receptor
C. Vasopressin receptor
D. Dopamine receptor
E. Mu receptor (Correct Answer)

Explanation: ***Mu receptor*** - The hormone described, which stimulates pigment production in neural crest-derived cells, is **melanocyte-stimulating hormone (MSH)**. - **MSH** is derived from the pro-opiomelanocortin (POMC) precursor, which also gives rise to **β-endorphin**, a potent opioid peptide that acts on **mu opioid receptors**. *TSH receptor* - The **TSH receptor** binds thyroid-stimulating hormone (TSH), which primarily regulates thyroid hormone production and is not directly related to pigment production or opioid co-secretion from POMC. - TSH is produced by the anterior pituitary but from a different lineage than POMC-derived hormones. *Glucocorticoid receptor* - The **glucocorticoid receptor** binds cortisol and other glucocorticoids, which are involved in stress response and metabolism. - While ACTH (also derived from POMC) can stimulate adrenal glucocorticoid release, the question specifically refers to a substance *cosecreted* with MSH, not one that is *regulated* by MSH or its derivatives. *Vasopressin receptor* - **Vasopressin receptors** bind antidiuretic hormone (ADH), which regulates water balance and blood pressure. - ADH is produced by the posterior pituitary (though synthesized in the hypothalamus) and is not cosecreted with MSH from the anterior/intermediate pituitary. *Dopamine receptor* - **Dopamine receptors** bind dopamine, a neurotransmitter involved in various functions, including the inhibition of prolactin release from the pituitary. - While dopamine can influence pituitary function, it is not cosecreted with MSH in the manner described, nor is it a direct product of POMC cleavage.

Question 6: A 65-year-old woman arrives for her annual physical. She has no specific complaints. She has seasonal allergies and takes loratadine. She had a cholecystectomy 15 years ago. Her last menstrual period was 9 years ago. Both her mother and her maternal aunt had breast cancer. A physical examination is unremarkable. The patient is given the pneumococcal conjugate vaccine and the shingles vaccine. A dual-energy x-ray absorptiometry (DEXA) scan is obtained. Her T-score is -2.6. She is prescribed a new medication. The next month the patient returns to her primary care physician complaining of hot flashes. Which of the following is the most likely medication the patient was prescribed?

A. Raloxifene (Correct Answer)
B. Denosumab
C. Teriparatide
D. Zoledronic acid
E. Alendronate

Explanation: ***Raloxifene*** - This patient has osteoporosis (T-score -2.6), increased **breast cancer risk** (family history), and postmenopausal status. **Raloxifene** is a **selective estrogen receptor modulator (SERM)** that treats osteoporosis and reduces breast cancer risk. - The medication's **estrogen-antagonist effect** in the hypothalamus can cause or worsen **hot flashes**, a known side effect that explains her new complaint. *Denosumab* - **Denosumab** is a **monoclonal antibody** that inhibits osteoclast function, effectively treating osteoporosis. - It works differently from SERMs and is **not associated with hot flashes** as a side effect. *Teriparatide* - **Teriparatide** is a **parathyroid hormone analog** that promotes bone formation, used for severe osteoporosis. - It is not a SERM and does **not cause hot flashes** as a typical side effect. *Zoledronic acid* - **Zoledronic acid** is a **bisphosphonate** that inhibits osteoclast activity, effectively treating osteoporosis. - While intravenous administration can cause flu-like symptoms, it is **not associated with hot flashes**. *Alendronate* - **Alendronate** is an **oral bisphosphonate** that reduces bone resorption in osteoporosis. - Its side effect profile mainly involves gastrointestinal issues and esophageal irritation, and it does **not cause hot flashes**.

Question 7: A researcher is studying receptors that respond to epinephrine in the body and discovers a particular subset that is expressed in presynaptic adrenergic nerve terminals. She discovers that upon activation, these receptors will lead to decreased sympathetic nervous system activity. She then studies the intracellular second messenger changes that occur when this receptor is activated. She records these changes and begins searching for analogous receptor pathways. Which of the following receptors would cause the most similar set of intracellular second messenger changes?

A. Muscarinic cholinoreceptors in the gastrointestinal tract
B. Growth hormone receptors in the musculoskeletal system
C. Vasopressin receptors in the kidney
D. Dopamine receptors in the brain (Correct Answer)
E. Aldosterone receptors in the kidney

Explanation: ***Dopamine receptors in the brain*** - The described presynaptic receptors for epinephrine that decrease sympathetic activity are **alpha-2 adrenergic receptors**, which are **G inhibitory protein (Gi)-coupled receptors**. - Gi-coupled receptors **inhibit adenylyl cyclase**, leading to a **decrease in intracellular cAMP**, a signaling pathway shared by **D2 dopamine receptors**. *Muscarinic cholinoreceptors in the gastrointestinal tract* - Most muscarinic receptors (M1 and M3) in the GI tract are **Gq-coupled**, leading to an **increase in phospholipase C (PLC) activity**, ultimately increasing intracellular **IP3 and DAG** and promoting smooth muscle contraction. - This mechanism is distinct from the **Gi-mediated inhibition of cAMP** described for the presynaptic adrenergic receptor. *Growth hormone receptors in the musculoskeletal system* - Growth hormone receptors are **tyrosine kinase-associated receptors** (specifically, they are linked to **JAK/STAT pathways**), not G protein-coupled receptors. - Their intracellular signaling involves **protein phosphorylation cascades**, which are fundamentally different from second messenger changes involving cAMP. *Vasopressin receptors in the kidney* - Vasopressin (ADH) acts on **V2 receptors** in the kidney, which are **G stimulatory protein (Gs)-coupled receptors**. - Activation of V2 receptors leads to an **increase in adenylyl cyclase activity** and thus an **increase in intracellular cAMP**, the opposite effect of the described Gi-coupled receptor. *Aldosterone receptors in the kidney* - Aldosterone receptors are **intracellular steroid hormone receptors** that directly bind to DNA and regulate gene transcription. - They do not engage in rapid intracellular second messenger changes like G protein-coupled receptors, but rather alter **protein synthesis** over hours to days.

Question 8: A 16-year-old female presents to your clinic concerned that she has not had her menstrual cycle in 5 months. She has not been sexually active and her urine pregnancy test is negative. She states that she has been extremely stressed as she is in the middle of her gymnastics season and trying to get recruited for a college scholarship. Physical exam is remarkable for a BMI of 16, dorsal hand calluses, and fine hair over her cheeks. What other finding is likely in this patient?

A. Normal menstrual cycles
B. Elevated estrogen levels
C. Low bone density (Correct Answer)
D. Polycythemia
E. Elevated TSH

Explanation: ***Low bone density*** - The patient's presentation suggests **anorexia nervosa** or **bulimia nervosa**, characterized by a low BMI, amenorrhea, and signs of purging (calluses from induced vomiting). - **Malnutrition**, particularly **estrogen deficiency** from amenorrhea, significantly impairs bone formation and increases bone resorption, leading to **osteopenia** or **osteoporosis**. *Normal menstrual cycles* - The patient has presented with **amenorrhea** (absence of menstrual cycles for 5 months), which is a key symptom indicating an underlying issue related to hormonal regulation due to stress and potential eating disorder. - Normal menstrual cycles would contradict the primary complaint and the clinical picture suggesting significant physiological stress. *Elevated estrogen levels* - **Amenorrhea** in this context is typically caused by **hypothalamic dysfunction** and **low gonadotropin-releasing hormone (GnRH)**, leading to reduced LH and FSH secretion, and subsequently **low estrogen levels**. - Elevated estrogen levels would likely result in regular menstrual cycles or other hormonal symptoms, which are not present here. *Polycythemia* - **Polycythemia** (an abnormally high concentration of hemoglobin in the blood) is not typically associated with eating disorders or amenorrhea. - While dehydration from purging could _transiently_ increase hematocrit, it does not lead to _true_ polycythemia, and sustained polycythemia is not a common complication of this presentation. *Elevated TSH* - **Elevated TSH** indicates **hypothyroidism**, which can cause weight gain, fatigue, and sometimes menstrual irregularities, but typically not such a low BMI or the specific physical exam findings like dorsal hand calluses and fine hair (lanugo-like hair, seen in eating disorders). - In eating disorders, the thyroid function is usually normal or shows **euthyroid sick syndrome** (low T3, normal TSH, normal T4), not primary hypothyroidism.

Question 9: A 66-year-old man comes to the physician because of a 3-month history of constipation and streaks of blood in his stool. He has had a 10-kg (22-lb) weight loss during this period. Colonoscopy shows an exophytic tumor in the sigmoid colon. A CT scan of the abdomen shows liver metastases and enlarged mesenteric and para-aortic lymph nodes. A diagnosis of stage IV colorectal cancer is made, and palliative chemotherapy is initiated. The chemotherapy regimen includes a monoclonal antibody that inhibits tumor growth by preventing ligand binding to a protein directly responsible for epithelial cell proliferation and organogenesis. Which of the following proteins is most likely inhibited by this drug?

A. VEGF
B. TNF-α
C. EGFR (Correct Answer)
D. ALK
E. CD52

Explanation: ***EGFR*** - The description of a monoclonal antibody preventing ligand binding to a protein responsible for **epithelial cell proliferation** and organogenesis strongly points to the **epidermal growth factor receptor (EGFR)**. - EGFR is highly expressed in many colorectal cancers and its activation by ligands like EGF promotes cell growth, survival, and metastasis. Inhibiting it reduces tumor progression. *VEGF* - **Vascular endothelial growth factor (VEGF)** is primarily involved in **angiogenesis**, the formation of new blood vessels. - While anti-VEGF therapies (e.g., bevacizumab) are used in colorectal cancer, their mechanism is inhibiting blood supply to the tumor, not directly blocking a receptor responsible for epithelial cell proliferation as described. *TNF-α* - **Tumor necrosis factor-alpha (TNF-α)** is a **cytokine** primarily involved in inflammation and immune responses. - Antibodies against TNF-α (e.g., infliximab) are used in inflammatory conditions like Crohn's disease, not typically as targeted therapy for colorectal cancer directly inhibiting epithelial proliferation. *ALK* - **Anaplastic lymphoma kinase (ALK)** is a **receptor tyrosine kinase** often implicated in lung cancer and lymphomas. - ALK rearrangements lead to oncogenic fusion proteins, but it is not a primary target for widespread epithelial cell proliferation in colorectal cancer. *CD52* - **CD52** is a glycoprotein found on the surface of various immune cells, including lymphocytes. - Antibodies targeting CD52 (e.g., alemtuzumab) are used in certain leukemias and lymphomas to deplete these cells, not for inhibiting epithelial cell proliferation in solid tumors.

Question 10: An investigator is studying vitamin D metabolism in mice. He induces a gene mutation that interferes with the function of an enzyme in the renal proximal tubules that is required for vitamin D activation. He then measures serum levels of various metabolites. Production of which of the following will be impaired in this mouse?

A. Ergocalciferol
B. Cholecalciferol
C. 7-dehydrocholesterol
D. 25-hydroxyvitamin D
E. 1,25-dihydroxyvitamin D (calcitriol) (Correct Answer)

Explanation: ***1,25-dihydroxyvitamin D (calcitriol)*** - This is the **biologically active form** of vitamin D, produced in the kidney by the **1α-hydroxylase enzyme** in the renal proximal tubules. - A mutation interfering with this enzyme would directly impair the conversion of 25-hydroxyvitamin D to **1,25-dihydroxyvitamin D**, the active form. - This enzyme adds the second hydroxyl group at position 1, creating the dihydroxy form (calcitriol). *Ergocalciferol* - This is **vitamin D2**, obtained from dietary sources (plants, supplements) and is not produced endogenously in the body. - Its production would not be directly affected by a renal tubular enzyme defect. *Cholecalciferol* - This is **vitamin D3**, primarily synthesized in the skin upon exposure to sunlight or obtained from animal-based dietary sources. - Its production occurs before any renal activation steps, so it would not be impaired. *7-dehydrocholesterol* - This is a **precursor molecule** in the skin that is converted to cholecalciferol (vitamin D3) upon UV radiation. - Its levels would not be directly affected by a defect in renal vitamin D activation. *25-hydroxyvitamin D* - This is the **storage form** of vitamin D, produced in the liver from cholecalciferol or ergocalciferol by the 25-hydroxylase enzyme. - Its production occurs prior to the renal activation step and would therefore not be impaired by a defect in the renal tubules.

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