Intro to Endocrine Flashcards
Hormones
secreted by endocrine glands and tissues
- effective at LOW [ ]
- autocrine, endocrine, and paracrine effects
- bind carrier proteins in serum
3 types of hormones
- peptide-protein
- Lipid
- Nonpeptide AA based
Bind to receptors on target cells
Free Hormone and Free Receptor form Hormone-Receptor complex
- reversible binding, saturable
- varying levels of specificity
- activates secondary messengers or transcription
Infundibulum
stalk that connects pituitary to brain
Posterior pituitary
extension of neural tissue –> controlled by hypothalamus and its hormones (ADH and oxytocin)
- hormones immediately enter circulation –> FAST response
Anterior pituitary
true endocrine gland of epithelial origin –> regulated by hormone secretion from hypothalamus (hypothalamo-pituitary endocrine axis)
- hypothalamic control is either releasing or inhibiting
- portal system
- may involve 3rd endocrine gland –> SLOW response
- hormone may act as (-) feedback regulator
Negative feedback regulation
most common mechanism
- limits amount of hormone release -> prevents snow-balling
Positive feedback regulation
Rare, reinforces snow-ball effect
Protein/peptide hormone synthesis
preprohormone synthesized and cleaved into prohormone in RER –> golgi further cleaves it into mature hormone –> packaged into secretory granules
- water soluble -> can be transported by carrier proteins but not required
Steroid hormone synthesis
derived from cholesterol -> converted to final product by enzymatic reaction (mito and smooth ER)
- produced and secreted without storage -> traverse cell membranes down [ ]
- not water soluble -> 99.9% bound to carrier proteins
Eicosanoids
biologically active lipid mediators
- signal through GPCR
- occur at low levels in tissues and are drugable targets
Hormones derived from arachdonic acid
- COX-1,2 –> prostaglandins
- 5-LO –> luekotrienes
- 12LO –> 12-HETE
- 15-LO –> 15-HETE
- Cyt P450 –> HETEs and epoxides
Amines
Catecholamines (tyrosine derived)
Thyroid Hormones -> act like steroids and bind receptors which also belong to nuclear receptor family
- production controlled by enzymes and iodine availability
Tryptophan hormones –> serotonin, melatonin
Down-regulating hormone signaling
- decreasing receptor #
2. increasing degradation of hormone cells
Up-regulating hormone signaling
- increase receptor #
2. decreasing intracellular degradation of hormone
Protein/peptide hormones
bind to receptors of target cell-membrane (tyrosine kinase)
- secondary messengers (guanosine triphosphate, AC -> cAMP, PLC -> DAG & IP3 , Ca2+)
Most protein hormone receptors are coupled to Gsalpha
Gsalpha -> AC -> increase cAMP -> PKA -> phosphorylation
Steroid signaling (nuclear receptor superfamily)
Estrogens Progesterones Androgens Glucocorticoids Mineralocorticoids
Unliganded RXR heterodimers with hormone
receptor complexes to activate transcription (transcription factor)
- thyroid hormones
- Vitamin D
- Eicosanoids, PGs, LTKs, FFAs
- FXR - bile acid receptor
- RAR - all trans retinoic acid
Ligand RXR homodimers
require hormone binding for transcriptional activation
- co-repressor is released with T3 binding
- co-activator binds to hormone/receptor complex
- transcription is modulated
Steroid signaling
- Free hormone dissociates from carrier protein and enters cell
- Hormone binds cytoplasmic receptor and translocates to nucleus
- Dimers form and sit on steroid response element
- Transcription
- Translation
- Hormone cellular response
Hormone Fates
Liver/Kidney metabolic degradation of circulating hormone
- carrier proteins extend half-life of hormones
Pulsatile secretion
hypothalamic and pituitary hormones are secreted in pulsatile pattern to prevent desensitization of downstream receptors
Continuous administration of hormones?
down regulates the hormone receptors and as a result the reduced hormone signaling ensues
Multiple Hormones?
can be additive, synergistic, permissive, antagonistic
