Growth Hormone Insulin-Like Growth Factor-1 (Prolactin and Dopamine) Flashcards
How is growth hormone (GH) released and what inhibits its release? What does GH stimulate and what is its effect?
- Hypothalamic secretion of growth hormone-releasing hormone (GHRH) or ghrelin stimulates release of growth hormone (GH)
- Somatostatin inhibits release of GH
- GH stimulates the liver to synthesize and secrete insulin-like growth factor 1 (IGF-1)
- IGF-1:
- promotes systemic growth
- inhibits GH release from the anterior pituitary gland
Growth hormone and IGF-1
What is GH and IGF-1?
GH
- is expressed at high concentrations during puberty
- is secreted in a pulsatile manner (large pulses at night during sleep)
- its anabolic effects are mediated by insulin-growth factors → IGF-1
- promotes lipolysis, gluconeogenesis and protein synthesis
IGF-1
- is released into the circulation by hepatocytes in response to stimulation by GH
- Both GH and IGF-1 promote skeletal and soft tissue growth
GH and IGF-1 Receptors
GH and IGF-1 receptors are similar in structure and action
What are GH deficiencies? Clinical manifestation? Diagnosis?
- Cause of retarded growth or possible dwarfism
- Can be:
- heritable or aquired
- a hypothalamic defect (GNRH defect)
- a pituitary problem → tumor, trauma, infection
Clinical manifestation: - Cardiovascular
- Psychosocial problems
- Decreased muscle and bone mass
- Increased body fat (face)
- Low energy and reduced strength
- Poor libido and sleep patterns
Diagnosis: - Measurement of serum GH levels (Basal and stimulated GH levels often needed)
GH Deficiency: Dwarfism
- Occurs when an individual organism is short in stature resulting from a medical condition caused by slow growth
- In humans dwarfism is less than 4ft 10in tall
- Disproportionate dwarfism is characterized by one or more body parts being relatively large or small in comparison to those of an average-sized adult, with growth variations in specific areas being apparent (Achondroplasia + GH deficiency)
- Proportionate dwarfism, the body appears normally proportioned, but is unusually small (GH deficiency)
What are the 3 therapy’s for Gh deficiencies?
- Recombinant human GH (rhGH) such as somatropin
- Mecasermin
- Sermorelin
GH Deficiency: Therapy - Recombinant human GH (rhGH) such as somatropin
- Recombinant human GH (rhGH) such as somatropin
- Given SC in the evening 3-7x/week
In children:
- Deficiencies such as chronic renal diseases (CRD)
- Turner’s syndrome
- These children would have their IGF-1 levels and their height monitored overtime and therapy would be continues until the growth spurt has ceased
In adults:
- GH deficiency
- AIDS wasting
- short bowel syndrome
- anti-aging
- GH therapy has shown to be abused in athletes due to its anabolic properties
GH Deficiency: Therapy - Mecasermin
- Mecasermin
- Used in children with:
- GH receptor defects
- antibodies to GH
- rhlGFBP → the binding protein responsible for maintaining IGF-1 half life
GH Deficiency: Therapy - Sermorelin
- Sermorelin - syntehtic form of GHRH
- it is not useful if the deficiency occurs at the level of the pituitary gland but it can be used diagnostically to differentiate between hypothalamic and pituitary disease
GH Excess causes what 2 things?
- Gigantism
- Acromegaly
- Diagnosed by elevated serum IGF-1 or GH and cause is usually associated with a tumor of the anterior pituitary
- Surgery successful if the tumor is microadenoma, otherwise radiation can be applied
GH Excess - Gigantism
- Gigantism
- Excessive linear growth when epiphyses of growth plates still unfused in young
- Very rare condition - significantly shortened life
GH Excess - Acromegaly
- Acromegaly (characterized by soft tissue swelling)
- GH excess in adulthood; uncommon
- Other conditions that might accompany:
- arthropathy (form of arthritis)
- visceromegaly (enlargement of abdominal organs)
- respiratory and cardiovascular problems
- gastrointestinal tumors
GH Excess: Drug Therapy
Octreotide (somatostatin analogue)
- inhibits GH release
- longer half-life than SST
- depot forms available
Pegvisomant (GH antagonist)
- decreases IGF-1
- newly approved; alternative to somatostatin analogs
- dopamine agonists
Prolactin and dopamine - what are they? receptors? release? effect?
- Prolactin is a peptide hormone produced in the anterior pituitary (lactotrophs)
- Prolactin receptor is similar to GH receptor struture
- Causes breast development and milk production following birth
- No treatment available for prolactin deficiencies; prolactin excess does not always result in adverse symptoms
- Too much prolactin (frequently because of a prolactin-secreting pituitary tumor) may cause inappropriate breast development and lactation (particularly problematic in men) as well as reproductive difficulties
- Dopamine is normally released by the hypothalamus to decrease prolactin secretion from the pituitary, so dopamine-like drugs can be used to decrease prolactin
- Pituitary prolactin secretion is regulated by endocrine neurons in the hypothalamus → the neurosecretory tuberoinfundibulum (TIDA) neurons of the arcuate nucleus that secrete dopamine (aka prolactin inhibitory hormone)
- Dopamine acts on the D2 receptors of lactotrophs, causing inhibition of prolactin secretion. In absence of dopamine, prolactin cells secrete prolactin continuously
- TRH has a stimulatory effect on prolactin release, however Prl is the only adenohypophyseal hormone whose principal control is inhibitory
