Pituitary Hormone Function Flashcards

1
Q

What is the process of creation and storage of growth hormone?

A

Similar to many other hormones, GH is synthesized as part of a prohormone. Once the signal peptide is cleaved, GH is stored in secretory granules of somatotrophs of the adenohypophysis. The synthesis of GH is evidently a major activity of the anterior pituitary, since 10% of the dry weight of the anterior pituitary is contributed by GH.

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2
Q

What controls the release of growth hormone?

A

Secretion of GH is under the influence of the hypothalamic hormones GHRH and somatostatin. GHRH and somatostatin stimulation of somatotrophs have opposing actions on cAMP levels; GHRH stimulation increases them, whereas somatostatin decreases them. Increased cAMP leads to the secretion of GH.

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3
Q

What receptors does growth hormone interact with?

A

At a cellular level, GH interacts with GH receptors in the plasma membrane of target cells. Both GH receptors and their signaling mechanisms are similar to that of PRL. Prolactin receptors are members of the growth hormone/cytokine receptor families. The long form of PRL receptors and the growth factor receptors are about 620 amino acids in length. They are single chain proteins crossing the membrane only once. Upon ligand binding, receptors dimerize, leading to the activation of the JAK/STAT pathway. Just as prolactin and growth hormone share structural homology, so do their receptors. Human PRL receptors are well stimulated by GH.

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4
Q

On what tissues does growth hormone have a direct action?

A

Adipose tissue
Muscle
Liver

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5
Q

What is the effect of growth hormone on adipose tissue?

A

The net effect is to increase lipolysis and lead to mobilization of lipid and thus an increase in plasma free fatty acids (FFAs). Eventually, the effect of GH on fat metabolism will be evidenced by a loss in subcutaneous fat. In this action GH antagonizes the action of insulin.

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6
Q

What is the effect of growth hormone on muscle tissue?

A

GH has a strong anabolic action on muscle. Amino acid transport is increased, and protein synthesis is increased.

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7
Q

What is the effect of growth hormone on the liver?

A

Increased RNA, protein and glucose synthesis. Further, IGF-I will be secreted, which mediates the indirect effects. The increase in glucose levels is mainly due to an increase in gluconeogenesis and not due to glycogenolysis.

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8
Q

What are the “large picture” general effects of growth hormone across all systems?

A

GH’s effects are anti-insulin like, i.e. glucose uptake will be decreased and plasma glucose levels will rise. The increased plasma FFA provides an alternate energy source and the increased plasma glucose is reserved for the CNS. Importantly, protein is spared. This contrasts with the actions of cortisol.

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9
Q

What are the indirect actions of growth hormone?

A

GH also has effects on muscle and skeletal growth mediated by another hormone-the Insulin-like growth factor (IGF). There are two forms of IGF that have been shown to exist (IGF-I and IGF-II). Of these, IGF-I is the predominant form in postnatal tissues. The production of IGF requires both GH and insulin and occurs in a number of tissues (e.g. liver, bone marrow).

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10
Q

What is the general structure and function of IGF-1?

A

IGF-I is structurally related to proinsulin (hence its name) and has many insulin like actions (especially in adipose tissue and muscle). IGF-I is a powerful mitogen and growth-promoting agent.

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11
Q

What type of receptors does IGF-1 bind to and what are their second messenger pathways?

A

IGF receptors belong to the EGF/ Insulin receptor family. These receptors contain an inherent tyrosine kinase activity and upon ligand binding can readily phosphorylate themselves (auto phosphorylation) and other proteins of the signal transduction pathway. The major pathway activated by IGF receptors is initiated by the binding of Insulin Receptor Associated proteins 1 and 2 (IRS I&II). IRS in turn can bind to other molecules to activate either the MAP kinase pathway or transduction mediated by PI-3 kinase.

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12
Q

What tissues does IGF-1 act upon?

A

Bone/Cartilage
Muscle
Adipose Tissue

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13
Q

What are IGF-1’s actions on bone/cartilage?

A

Long bone growth is promoted by the stimulated proliferation of epiphyseal cartilage. After puberty, the epiphyses seal and IGF-I no longer has this effect on linear growth.

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14
Q

What are IGF-1’s actions on muscle?

A

Stimulates proliferation, differentiation and protein synthesis

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15
Q

What are IGF-1’s actions on adipose tissue?

A

Stimulates uptake of glucose and inhibits lipolysis. This action of IGF is insulin like and antagonizes that of GH.

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16
Q

What are the control points in the growth hormone pathway?

A

Brain:
Circadian rhythms, stress

Hypothalamus:
GHRH (++++) Somatostatin (—)

Anterior Pituitary:
Growth hormone (negative feedback to pituitary, causes increased Somatostatin release)

Target Organs:
e.g. Liver: IGF-1 (negative feedback to hypothalamus to increase Somatostatin release and by inhibiting GHRH at the anterior pituitary)

17
Q

What other states, metabolites, drugs, or hormones stimulate growth hormone secretion?

A

Hypoglycemia, amino acids (arginine), low free fatty acid levels, α-adrenergic agonists (clonidine), β-adrenergic antagonists (propranolol) and estrogens.

18
Q

What other states, metabolites, drugs, or hormones inhibit growth hormone secretion?

A

Hyperglycemia, high free fatty acid levels, obesity, α-adrenergic antagonists, β-adrenergic agonists as well as pharmacological doses of corticosteroids inhibit GH secretion.

19
Q

How are levels of growth hormone assessed in a patient?

A

In assessing GH levels and secretion, it is important to obtain measurements several times over the course of a day. Stimulation of GH secretion by exercise or high doses of arginine is often used to assess GH status. In addition, measurement of IGF-I levels is very helpful, especially since its levels are subject to less diurnal variation.