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Flashcards in Intro to Endocrine Deck (25):
1

Hormones

secreted by endocrine glands and tissues
- effective at LOW [ ]
- autocrine, endocrine, and paracrine effects
- bind carrier proteins in serum

2

3 types of hormones

1. peptide-protein
2. Lipid
3. Nonpeptide AA based

3

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

4

Infundibulum

stalk that connects pituitary to brain

5

Posterior pituitary

extension of neural tissue --> controlled by hypothalamus and its hormones (ADH and oxytocin)
- hormones immediately enter circulation --> FAST response

6

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

7

Negative feedback regulation

most common mechanism
- limits amount of hormone release -> prevents snow-balling

8

Positive feedback regulation

Rare, reinforces snow-ball effect

9

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

10

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

11

Eicosanoids

biologically active lipid mediators
- signal through GPCR
- occur at low levels in tissues and are drugable targets

12

Hormones derived from arachdonic acid

1. COX-1,2 --> prostaglandins
2. 5-LO --> luekotrienes
3. 12LO --> 12-HETE
4. 15-LO --> 15-HETE
5. Cyt P450 --> HETEs and epoxides

13

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

14

Down-regulating hormone signaling

1. decreasing receptor #
2. increasing degradation of hormone cells

15

Up-regulating hormone signaling

1. increase receptor #
2. decreasing intracellular degradation of hormone

16

Protein/peptide hormones

bind to receptors of target cell-membrane (tyrosine kinase)
- secondary messengers (guanosine triphosphate, AC -> cAMP, PLC -> DAG & IP3 , Ca2+)

17

Most protein hormone receptors are coupled to Gsalpha

Gsalpha -> AC -> increase cAMP -> PKA -> phosphorylation

18

Steroid signaling (nuclear receptor superfamily)

Estrogens
Progesterones
Androgens
Glucocorticoids
Mineralocorticoids

19

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

20

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

21

Steroid signaling

1. Free hormone dissociates from carrier protein and enters cell
2. Hormone binds cytoplasmic receptor and translocates to nucleus
3. Dimers form and sit on steroid response element
4. Transcription
5. Translation
6. Hormone cellular response

22

Hormone Fates

Liver/Kidney metabolic degradation of circulating hormone
- carrier proteins extend half-life of hormones

23

Pulsatile secretion

hypothalamic and pituitary hormones are secreted in pulsatile pattern to prevent desensitization of downstream receptors

24

Continuous administration of hormones?

down regulates the hormone receptors and as a result the reduced hormone signaling ensues

25

Multiple Hormones?

can be additive, synergistic, permissive, antagonistic