E/G/R exam 3

true or false: glands and target tissues are all connected to each other through the circulatory system in the endocrine system

true

exocrine gland cells secrete compounds into _____

ducts

examples of exocrine glands

-sweat

-saliva

-pancreatic juices

endocrine glands can either store and secrete compounds or can continuously synthesize and release hormones into the ____

bloodstream

examples of compounds/hormones secreted by the endocrine glands

-growth hormone

-insulin

-estrogen

-cortisol

function of hormones

-regulation of energy production, utilization, and storage

-adaptation of growth and development

-control of reproductive system

hormone defintion

products of ductless glands (endocrine hormones)

chemical types of hormones

-steroids

-amino acid derivatives

-peptides

-proteins

example of a steroid hormone

estradiol

example of an amino acid derivative hormones

thyroxine

examples of a peptide hormone

glucagon

classification of a peptide

polypeptides with less than 50 AA

classification of proteins

polypeptides with more than 50 AA

example of protein hormone

chorionic gonadotropin

steps of hormonal communication

-synthesis

-release

-transport

-detection

-response

-removal

TSH _____ the hypothalamus

inhibits

thyroid hormones _____ the hypothalamus and anterior pituitary

inhibits

the hypothalamus releases TRH to _____ the anterior pituitary

stimulates

the anterior pituitary releases TSH to ____ the thyroid gland

stimulate

the thyroid gland releases thyroid hormones to _____ target cells

stimulate

molecular mechanisms of hormone signal transduction

-tyrosine kinase receptors

-G-protein coupled receptors

-nuclear receptors

what hormones bind to cell surface receptors and affect signaling inside the cell

peptide and protein

the hormone does or does not usually enter the cell to initiate cell signaling

does not

two type of cell surface receptors

-tyrosine kinases receptors

-G-protein coupled receptors

binding of the hormone to the to GPCR activated the Galpha-subunit activates enzymes that do what

change the concentrations of secondary messenger molecules

examples of secondary messenger molecules

cAMP, Ca, IP3, DAG, NO

result of GPCR signaling cascades

changes in the activity of enzymes/transporters/ion channel and changes in gene expression

what GPCR protein class activates PLC, increases IP3 and DAG, and increases Ca

Galpha(q) (Gq)

tyrosine kinase receptor signaling

1. Hormone binding activates the receptor

2. The receptor phosphorylates its partner or an associated substrate

3. The phosphorylated protein / receptor is recognized by adaptor proteins or other kinases

4. A sequential cascade of phosphorylation events leads to changes on gene expression

metabolism of non-peptide/protein hormones

CYPs in the liver

hormones show a concentration _____ activity

dependent

what gland produces and releases melatonin

pineal gland

melatonin secretion is controlled by _____ and maintain the ______

light, circadian rhythm

what does melatonin block the secretion of

gonadotropins from the anterior pituitary

what is the link between the nervous system and endocrine system

hypothalamus

what is the regulator of the pituitary gland

hypothalamus

neurons of the hypothalamus reach directly into what

the posterior pituitary gland, considered an extension of the hypothalamus

what hormones are produced by the hypothalamus and released into the portal vein to the anterior pituitary

-TRH

-CRH

-DA

-CnRH

-GHRH

-GHIH

TRH

thyrotropin releasing hormone

CRH

corticotropin releasing hormone

DA

dopamine

GnRH

gonadotropin releasing hormone

GHRH

growth hormone releasing hormone

GHIH

growth hormone inhibiting hormone

what hormones are produced by the hypothalamus and release from extended hypothalamic neurons in the posterior pituitary

-ADH

-oxytocin

what hormones are produced and released by endocrine cells in the anterior pituitary gland

-LH

-FSH

-PRL

-GH

-ACTH

-TSH

-MSH

LH

luteinizing hormone

FSH

follicle-stimulating hormone

PRL

prolactin

GH

growth hormone

ACTH

adrenocorticotropic hormone

TSH

thyroid stimulating hormone

MSH

melanocyte-stimulating hormone

what hormones are produced by neuronal cells in the hypothalamus but stored by and released from posterior pituitary gland

-ADH

-Oxytocin

what is growth hormone synthesized and secreted by

somatotropes

GH is a _____ hormone

protein

what is GH stimulated by

GHRH

GH release is inhibited by _____

somatostatin

GH is secreted in _____ but irregular pulses

discrete

what does GH stimulate the release of

IGF-1 from the liver

GH and IGF-1 form a _____ feedback loop to reduce GH production and release

negative

true or false: somatostatin does not downregulate GH release

false

excess production of GH is a result of

somatotrope adenoma

clinical manifestation of excess growth hormone

-gigantism in juveniles

-acromegaly in adults

pharmacological approaches to treat GH overproduction

-SST analogs

-SST receptor agonists

-GH receptor antagonists

how many somatostatin receptors are there

5 (SSTR1-5)

SST receptor agonist

-octreotide

-lanreotide

-pasireotide

Sandostatin

octreotide

indication of octreotide

treat carcinoid (metastatic neuroendocrine tumor) syndrome (flashing, diarrhea)

octreotide binds to what somatostatin receptors

SSTR2 and SSTR5

side effects of octreotide

-D/N

-abdominal pain

-can develop gallstones

-sinus bradycardia

-conduction disturbance

Somatuline LA

lanreotide, long acting octapeptide

Somatuline depot

Lanreotide in a supersaturated aqueous formulation autogel

Signifor LAR

Pasireotide, long acting cyclohexapeptide

what drug has high binding affinity to 4 of the 5 SSTRs

pasireotide

what drug is has pamoic acid as a counter ion, and is embedded into microspheres of poly(D,L-lactide-co-glycolide as a stabilizer

pasireotide

warnings and precautions of lanreotide, octreotide, and pasireotide

-gall stones

-hyper and hypoglycemia may occur

-bradycardia, arrhythmia

-hypothyroidism

drug interactions of lanreotide, octreotide, and pasireotide

-diabetes drugs

-cyclosporin

-beta blockers

-bromocriptine

Somavert

Pegvisomant

GH receptor antagonist

Pegvisomant

pegylated derivative of GH with amino acid substitutions in 9 positions

pegvisomant

what drug does not lead to signaling through JAK and blocks native GH from binding to the GHR (competitive agonist)

pegvisomant

warnings and precaution with pegvisomant

monitor liver function

drug interactions of pegvisomant

-diabetes drugs, may need reduction

-opioids, may need higher doses to achieve appropriate IGF-1 suppression

causes of GH deficiency

-genetic mutations in GHRH, GHRHR, GH, GHR

-damage to pituitary gland

consequences of GH deficiency

-slow growth and short stature of children

-hypoglycemia

-in adults: obesity, reduced muscle mass, asthenia, reduced cardiac output

primary therapeutic objective in pediatric patients with:

-GH deficiency

- Chronic renal failure

- Noonan syndrome

- Prader-Willi syndrome

- Short stature homeobox containing gene deficiency

- Turner syndrome

- Small for gestational age with failure to catch up by age 2 years

- Idiopathic short stature in pediatric patients

normalizing/augmenting growth and development

primary therapeutic objective of GH deficiency in adults

improved metabolic state, increased lean body mass, sense of well being

primary therapeutic objective of wasting in patients with HIV infection

increased lean body mass, weight, and physical endurance

primary therapeutic objective in patients with short bowel syndrome and are also receiving specialized nutritional support

improved GI function

GH preparations match what native GH (ex. SEROSTIM, GENOTROPIN, HUMATROPE, NUTROPIN, SAIZEN)

somatropin

GH with additional Met at N-terminus (PROTROPIN)

somatrem

SOGROYA generic approved in 2020 for use in adults, fatty acid conjugate

somapacitan-beco

SKYTROF 2021, approved in 2021 for pediatric use, PEG conjugate, prodrug

lonapegsomatropin-tcgd

contraindications of all GH drugs

-acute critical illness or malignancy

-diabetic retinopathy

warings and precautions for GH drugs

-continue HIV therapy

-monitor glucose levels

-monitor all patients with cancer history

-consider pancreatitis in patients with persistent severe abdominal pain

drug interactions of GH drugs

-Inhibition of a steroid synthesis enzyme, patients may need increased doses of glucocorticoids or oral estrogens

- Cytochrome P450 metabolized drugs: monitor carefully

what are some possible causes of GH deficiency that cannot be treated with GH therapy

-mutations in GH receptor that prevent GH action

-anti-GH antibodies

-mutations in IGF-1 gene or IGF-1 binding protein

therapeutic option for GH deficiency that cannot be treated with GH therapy

IGF-1 can be supplemented directly and has similar effects as GH therapy

Increlex generic

Mecasermin