Endocrine 1: basics Flashcards
Characterize a classical endocrine organ.
- ductless
- secretes hormones directly into bloodstream (highly vascularized)
- entire organ is primarily dedicated to endocrine functions
List the classical organs.
- pineal
- pituitary
- thyroid
- parathyroid
- adrenal
- ovary/testes
- pancreas endocrine portion
What is unique about classical endocrine organs?
because of their ductless features, you can place them anywhere in the body and they would still function, provided they have enough vasculature
List the non-classical endocrine organs.
- brain, hypothalamus
- kidney: renin, EPO, vitamin D
- heart: ANP
- liver: IGF1
- GI: serotonin, ghrelin
- adipose: leptin
Define hypersensitivity.
- overproduction of a hormone leads to hypersensitivity to its effect (increased receptors)
Define hyposensitivity.
- decreased production of a hormone and decreased receptors leads
Describe the importance of the target receptor.
- it is the activity of the receptor that carries out endocrine function, not the hormone itself
- wherever there is a receptor, that hormone will have an effect
- in the presence of molecules that are structurally similar to the receptor’s hormone => will cause the effect in the right conditions
- target cell response depends on the ratio of hormone to receptor
How is the endocrine system integrated into the immune system?
- all hormones effect the thymus
- immune cells have receptors for hormones
Characterize endocrine pathologies.
- defect in endocrine organs (primary = classical organ; secondary/tertiary = downstream organs)
- hormone imbalance (hyper or hyposecretion)
- vague symptoms
- long time to develop
Differentiate between congenital and genetic.
- genetic: inherited
- congenital: present at birth, not necessarily inherited
Describe cretinism.
- congenital
- iodine deficiency during development
- leads to thyroid deficiency
- symptoms = short stature, mental retardation, impaired bone formation, delayed motor development
- tx = iodine supplementation
Describe Multiple Endocrine Neoplasia (MEN).
- genetic
- 2-3 tumors in multiple endocrine glands
- inherited through MEN1 gene
Why are tumors prevalent in endocrine pathology?
- highly vascularized organs
- high rates of turnover
Why is small cell lung carcinoma considered an endocrine pathology?
- lung is not an endocrine organ
- tumor secretes endocrine hormones and leads to endocrine pathological symptoms
Describe Sheehan’s Syndrome.
- stress related
- during pregnancy, pituitary increases in size
- during childbirth, shock and hemorrhage lead to pituitary cell death
List etiologies of endocrine pathologies.
- congenital
- genetic
- stress/trauma
- tumors
- infections/autoimmune
- environmental factors
- surgical
- therapeutic
What is the most common endocrine pathology?
Type 2 Diabetes Mellitus
Define the 3 mechanisms of hormone action.
- endocrine: blood => downstream tissue
- paracrine: ISF => nearby cells
- autocrine: ISF => same cell
Describe the regulation of endocrine pathway signaling.
- organ synthesizes and secretes non-specific hormone
- travels in bloodstream to the entire body (dilution becomes a factor)
- If it comes in contact with non-target organs, it becomes metabolized
- if it comes in contact with target organs, the receptor lends specificity and determines downstream effects and intensity
Why do endocrine organs release a large amount of hormone?
- dilution in the bloodstream
- must beat metabolism of hormone at non-target organs
What are the 2 states in which hormones are found in the blood?
- free (not bound to protein; or bound to albumin)
- bound (not biologically active)
What is the purpose of the hormone binding proteins?
- facilitate transport
- increase half-life by slowly releasing the hormone
- mainly for steroids and other lipophilic hormones
List some specific hormone binding proteins.
- Sex Hormone Binding Globulin (SHBG) binds to estrogen/testosterone
- Corticotropin Binding Globulin (CBG) binds to cortisol/corticosterone
- Thyroid Binding Globulin (TBG) and TransThyRetin (TTR) bind to thyroid hormone
What are the 2 ways hormones are delivered to target cells?
Scenario 1
- free hormone released at the cell membrane
- diffuses into the cell
- find intracellular targets
Scenario 2
- hormone/protein complex binds to megalin protein receptor on the cell surface
- endocytosis of complex
- hormone released from the vesicle at intracellular target
What do hormone receptors determine?
- specificity
- duration of hormone activity (internalization of cell surface receptors, ubiquitinization of intracellular receptors)
- no receptor = no action
- autoregulation by ligand
.Distinguish between specificity and affinity.
specificity - ability to distinguish between similar substances
affinity - ability to hold on to it
Define Kd and Ki.
Kd = determines affinity; ligand concentration needed to fill up 50% of the receptor binding sites
- the higher Kd, lower affinity
- the lower Kd, higher affinity
Ki = determines specificity; determines ability of a ligand to displace an existing bound ligand
- the higher the Ki, lower specificity
- the lower the Ki, higher specificity
Characterize lipophobic hormone receptors.
- cell surface
- second messenger pathways (cAMP, GPC)
- rapid internalization or degradation
List examples of lipophobic hormone receptors.
- GPC for most protein hormones
- receptor linked kinases for GH, prolaction, and EPO
- receptor kinases for insulin, ANP
Characterize lipophilic hormone receptors.
- intracellular
- bound to heat shock chaperone proteins in the cytoplasm
- slow response b/c requires transcription and translation
- act as transcription factors that activate or repress
Provide an example of a lipophilic hormone receptor.
Thyroid Hormone Receptor
- hormone binds to nuclear receptor
- in the absence of ligand = transcription repressed
- in the presence of ligand = transcription activated
List factors affecting hormone bioavailability.
- hormone transport (free vs bound; kinetics of half-life)
- target tissue (receptors, heat shock proteins)
- hormone synthesis/release (enzymes, processing)
- regulatory mechanisms (feedback, rhythms, aging, metabolism)
