Growth hormone insulin-like growth factor-1 prolactin dopamine≥/

hypothalamic-pituitary-growth hormone axis

what stimulates the release of growth hormone (GH)

hypothalamic secretion of growth hormone-releasing hormon (GHRH) or ghrelin

what inhibits the release of GH

somatostatin

what does GH stimulate

the liver to synthesize and secrete insulin-like growth factor-1

what does IGF-1 do

• promotes systemic growth

• inhibits GH release from the anterior pituitary gland

when is GH expressed at high concentrations

during puberty

in which manner is GH secreted

in a pulsatile manner (large pulses at night during sleep)

what are GH’s anabolic effects mediated by

Insulin like growth factors → IGF-1

what does GH promote

lipolysis, gluconeogenesis and protein synthesis

IGF-1 is released into the circulation by what

hepatocytes in response to stimulation by GH

what do both GH and IGF-1 promote

skeletal and soft tissue growth

what are GH and IGF-1 receptors similar in

structure and action

GH deficiency

cause of retarded growth or possibly dwarfism

• can be heritable or acquired

• can be: a hypothalamic defect (GHRH defect), a pituitary problem → tumor, trauma, infection

clinical manifestation of GH deficiency

• cardiovascular

• psychosocial problems

• decreased muscle and bone mass

• increased body fat (face)

• low energy and reduced strength 

• poor libido and sleep patterns

diagnosis of GH deficiency

• measurement of serum GH levels (basal and stimulated GH levels often needed)

dwarfism occurs when

an individual is short in stature resulting from a medical condition caused by slow growth

Disproportionate dwarfism is characterized by

one or more of the body parts being relatively large or small in comparison to those of an average size 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)

Therapy for GH deficiency

1. Recombinant human Gh (rhGH) such as somatropin (Accretropin) 

2. Mecasermin (rhIGF-1/rhIGFBP-3)

3. Sermorelin (synthetic form of GHRH)

recombinant human GH (rhGH) - somatotropin (Accretropin)

given SC in the evening (3-7X/week)

what is Somatropin given to children for

• deficiencies such as chronic renal disease (CRD)

• turner’s syndrome

these children would have their IGF-1 levels and their height monitored over time and therapy would be continues until the growth spurt has ceased

why would somatropin be given to adults

• GH deficiency

• AIDS wasting

• short bowel syndrome

• anti-aging

why has GH therapy been abused in athletes

due to its anabolic properties

when is Mecasermin used (rhIGF-1/rh;GFBP-3)

in children with 

• GH receptor defects 

• antibodies to GH

what is rhlGFBP

the binding protein responsible for maintaining IGF-1 half lfe

when is Sermorelin (synthetic form of GHRH) used

it is not useful if the deficiency occurs at the level of the pituitarygland but it can be used diagnostically to differentiate between hypothalamic and pituitary disease → if successful, would be @ the hypothalamic level, nt pituitary

GH excess

1. Gigantism

2. Acromegaly

gigantism

excessive linear growth when epiphyses of growth plates still unfused in young 

very rare condition - significantly shortened life

acromegaly

characterized by soft tissue swelling

GH excess in adulthood; uncommon

other conditions that might accompany acromegaly

• arthropathy (form of arthritis)

• visceromegaly (enlargement of abdominal organs)

• respiratory and cardiovascular problems

• gastrointestinal tumors

how is 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 also be applied

GH excess drug therapy

• Octreotide 

• Pegvisomant

Octreotide (generic, sandostatin, somatostatin analogue)

• inhibits Gh release

• longer halflife than SST 

• depot forms available

Pegvisomant (somavert; GH antagonist)

• decreases IGF-1

• Newly approved; alternative to somatostatin analogs

• dopamine agonist

prolactin

a peptide hormone produced in the anterior pituitary (lactotrophs)

what receptor is prolactin receptor similar to

GH receptor

what does prolactin do

causes breast development and milk production following birth

treatment for prolactin deficiency

there is no treatment for prolactin deficiency; prolactin excess does not always result in adverse symptoms

what may too much prolactin cause

too much prolactin (frequently bc of a prolactin secreting pituitary tumor) may cause inappropriate breast development and lactation (particularly problematic in med) as well as reproductive difficulties

what is dopamine normally released by and what does it do

dopamine normally released by the hypothalamus to decrease prolactin secretion from the pituitary, so dopamine-like drugs can be used to decrease prolactin

what is pituitary prolactin secretion regulated by

endocrine neurons in the hypothalamus → the neurosecretory tuberoinfundibulum (TIDA) neurons of the arcuate nucleus that secrete dopamine (aka prolactin inhibitory hormone)

what receptors does dopamine act on and what does it cause. what happens in the absence of dopamine?

dopamine acts on D2 receptors of lactotrophs, causing inhibition of prolactin secretion 

in absence of dopamine, prolactin cells secrete prolactin continuously

what effect does TRH have on prolactin release

TRH has a stimulatory effect on prolactin release, however, Prl is the only adenohypophyseal hormone whose principal control is inhibitory

prolactin and dopamine: drug therapy

dopamine-like drugs can be used to decrease prolactin

what are drugs used to decrease prolactin

Bromocriptine and cabergolide

what do bromocriptine and cabergolide do

• stimulate D2 dopamine receptors in the anterior pituitary to decrease prolactin secretion

• used if an individual is diagnosed with prolactin secreting tumour (prolactinoma)

• administration of dopamine analogues includes oral, intravaginal (reduces nausea observed with oral form) and subcutaneous deposits which are longer acting

acromegaly can also result following what

development of a pituitary tumor that may secrete GH and prolactin

growth hormone and prolactin -

related protein hormones released by anterior pituitary

GH stimulates

growth, directly and indirectly via IGF-1 synthesis in the liver

GH controlled by

somatostatin (-ve) and GH releasing hormone (+ve) from hypothalamus

GH deficiency

dwarfism in development; excess: gigantism in development, acromegaly in adulthood

prolactin stimulates what

lactation, controlled by hypothalamic dopamine (-ve), inhibits reproduction

prolactin excess (pituitary microadenoma, common in women)

stimulates breast, causes infertility

excess GH in acromegaly can be inhibited by what

somatostatin analogs, or dopamine D2 (pituitary dopamine receptor) agonists because of similarity between GH producing and prolactin producing cells

D2 agonists (many drugs, bromocriptine main example)

inhibit Gh and prolactin secretion

Main D2 drug uses:

suppression of prolactin from pituitary microadenoma, restoration of fertility in hyperprolactinemic pts