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Flashcards in Hormones and receptors Deck (12):
1

Paracrine vs autocrine effectors

paracrine acts on neighborin cells

autocrine acts on the same cell that secretes it

2

endocrine gland produces...

hormones

3

3 categories of hormones

1. derivatives of tyrosine (epi, norepi,dopamine, thyroxine)
2. derivatives of cholesterol (steroids): (testosterone, cortisol, estrogens, aldosterone, Vit D, progesterone)
3. peptides (oxytocin, vasopressin, angiotensin, TRH, GRH) and proteins (insulin, glucagon, GH, ACTH, prolactin, TSH)

4

Peptide and protein hormone secretion

-Synthesis as pre-prohormone on ribosomes
-then targeted to rough ER
-cleaved
-transported to Golgi: processed and packaged into secretory vesicles
-Ca dependent exocytosis (intracellular Ca rises, vesicles fuse to plasma membrane and release hormone)

Most transported in blood as free molecules (not GH, prolactin, or IGF). Half life limited by proteases

5

Classification by hormone function

1. regulation of water and mineral metabolism (Vit D, Aldosterone, Vasopressin)
2. regulation of energy metabolism (insulin, glucagon, cortisol)
3. regulation of reproduction (estrogen, testosterone , progesterone)
4. regulation of growth (GH, testosterone, estrogen)

6

Precursor for steroid hormones

cholesterol

7

Steroid hormone release

-synthesized and immediately released into blood stream (hydrophobic and lipophilic and thus membrane permeant)
-in blood: free (1-5%) vs bound form:
bound to HBG (hormone binding globulin)
-free form is biologically active (free level is regulated/sensed)
-bound form= reservoir (>90%)
-half lives on order of many hours to days (longer than protein/peptide)

8

2 major methods for measuring hormone levels

1. bioassays: measure hormone activity and in this case hormone function is measured by using an exogenous system e.g. cell lines, to measure hormone activity

2. immunoassays: Radio-immunoassays (RIA) and enzyme linked immunosorbent assays (ELISA) measure antibody binding to a specific region of the hormone. They might not be useful if an abnormal form of the hormone is being secreted by the patient.

Downside: don't know FUNCTIONAL amount (but in practice it works pretty well)

Common ELISA enzyme: alkaline phosphatase

9

What happens when protein and peptide hormones reach target? (hydrophilic hormone receptors)

Epi/norepi:
-activate G-protein coupled receptors
-results in changes in intracellular 2nd messengers (cAMP, diacylglycerol, inositol phosphates)
3 kinds of G proteins:
Gs (stimulatory; alpha subunit activates adenylate cyclase, increases cAMP)
Gi (inhibitory; counters actions of Gs; decreases adenylate cyclase and cAMP)
Gq (activates phospholipase C, then breaks down phosphatidyl inositol to generate IP3-- to mobilize Ca-- and DAG-- PKC)

GH/prolactin:
-receptors belong to JAK/STAT or "cytokine family" of receptors
-coupling and activation of tyrosine kinase (Janus kinase or JAK), which then causes phosphorylation of signal transducers and activators of transcription (STATs)

Insulin and IGF-1:
-EGF family
-tyrosine kinase receptors
-receptors are tyrosine kinases that are activated upon hormone binding.

10

Steroid receptors

Location of receptors: intracellular (nuclear)
-receptor-hormone complexes bind to specific hormone responsive elements (HRE) and activate transcription of specific genes.

11

Classes of feedback loops determining set points for hormone levels

1. Hormone level is regulated variable
Ex. thyroid hormone itself has negative feedback on hypothalamus
2. Plasma concentration of metabolite or mineral acts as regulated variable
Ex. Glucose kept b/t 80-100 mg/dL. Beta cells sense this and secrete insulin when too high or alpha cells secrete glucagon when glucose too low

Negative feedback loops common
Positive feedback loops rare (ex. production of oxytocin during birthing process)

12

Hormone levels

-pulsatile regulation over minutes
-circadian regulation throughout day
-downregulation of receptor can occur after binding