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Zorluk: OrtaEndocrine and Metabolic Mechanisms

A 42-year-old man presents to the outpatient clinic with a 2-year history of worsening joint pain, excessive sweating, and an increase in his shoe size. On physical examination, he has a prominent brow, macroglossia, and enlarged, doughy hands. Visual field testing is normal. Laboratory evaluation reveals a markedly elevated serum insulin-like growth factor-1 (IGF-1) concentration. Following administration of a 75-gram oral glucose load, serum growth hormone (GH) levels remain elevated. The hormone directly responsible for the peripheral somatic changes observed in this patient exerts its cellular effects via which of the following intracellular signaling mechanisms?

  1. A
    Dimerization of receptors and recruitment of cytoplasmic Janus kinases
  2. B
    Activation of phospholipase C and generation of inositol trisphosphate
  3. Autophosphorylation of intrinsic receptor tyrosine kinase residuesCevap
  4. D
    Ligand binding to a cytosolic receptor with subsequent nuclear translocation
  5. E
    Activation of a stimulatory G-protein and adenylyl cyclase

Cevap

The correct answer is autophosphorylation of intrinsic receptor tyrosine kinase residues.
This patient presents with classic signs of acromegaly, a condition typically caused by a growth hormone (GH)-secreting anterior pituitary adenoma. The excess GH stimulates the liver to synthesize and release insulin-like growth factor-1 (IGF-1). While GH has direct metabolic actions (e.g., insulin resistance, lipolysis), IGF-1 is the hormone directly responsible for the peripheral somatic manifestations of acromegaly, such as skeletal overgrowth, macroglossia, and soft tissue enlargement. The IGF-1 receptor is a receptor tyrosine kinase that is structurally highly homologous to the insulin receptor. When IGF-1 binds to its cell membrane receptor, it induces a conformational change that leads to the autophosphorylation of intrinsic intracellular tyrosine residues. This initiates a complex intracellular signaling cascade, primarily involving the PI3K/AKT and MAPK pathways, which promotes cellular growth, proliferation, and survival.

Adım Adım Çözüm

1
Diagnose the clinical condition.
The clinical presentation (somatic overgrowth, macroglossia) and lab findings (elevated IGF-1, failure of GH to suppress with glucose) are classic for acromegaly.
Establishing the diagnosis identifies the primary pathophysiological axis (GH/IGF-1 axis).
2
Identify the specific hormone asked about in the question.
The question asks for the signaling mechanism of the hormone directly responsible for the peripheral somatic changes, which is insulin-like growth factor-1 (IGF-1), not growth hormone (GH).
While GH is secreted by the pituitary adenoma, it acts primarily on the liver to stimulate the production of IGF-1. IGF-1 mediates the vast majority of the peripheral tissue growth seen in acromegaly.
3
Determine the intracellular signaling pathway of the identified hormone.
IGF-1 binds to the IGF-1 receptor, which is a receptor tyrosine kinase structurally homologous to the insulin receptor. Ligand binding induces autophosphorylation of intrinsic tyrosine residues.
Knowing specific hormone receptor classes is essential for foundational science applications in endocrinology.

Anahtar Kavram

Insulin-like growth factor-1 (IGF-1) mediates the peripheral somatic changes of acromegaly by binding to a receptor tyrosine kinase, leading to intrinsic autophosphorylation.
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Endocrine and Metabolic Mechanisms

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