Endocrine Systems & Receptors Flashcards
Hypothalamus + pituitary gland are secreted by
Peptide
thyroid + parathyroid glands are secreted by
Peptide and amine hormone secretion
adrenal glands are secreted by
Steroid and amine secretion
pancreas secreted by
peptide
ovaries + testes are secreted by
steriod
The Endocrine System
Classically consists of ductless endocrine glands
(c.f. exocrine glands)
The Endocrine System- communication
Communication between glands and other tissues, often at a distance, occurs by the secretion of a hormone into the bloodstream and bulk transport to a target site
The Endocrine System- signalling (3)
Specificity of signalling is achieved by:
(i) chemically distinct hormones
(ii) specific receptors for each hormone
(iii) distinct distribution of receptors across target cells
Examples of chemical signalling (3)
Autocrine-Cell signals to itself
Paracrine-Cell signals to its close neighbours
Endocrine-Cell signals via molecules transported by the blood to target distant cells
Hormone Synthesis, Storage, Release and Transport 1-(4)
Amines:
-are hydrophilic+ are transported mainly ‘free’ in plasma
-pre-synthesised, stored in vesicles
-released in response to stimuli by Ca2+-dependent exocytosis
Hormone Synthesis, Storage, Release and Transport 2- (4)
Peptides:
-are hydrophilic + are transported mainly ‘free’ in plasma
-pre-synthesised usually from a longer precursor, stored in vesicles
-released in response to stimuli by Ca2+-dependent exocytosis
Hormone Synthesis, Storage, Release and Transport
3- (7)
Steriods:
-hydrophobic + are transported in plasma mainly bound (~90%) to plasma proteins – only ‘free’ is biologically active
-synthesised and secreted upon demand
-stimuli increase=
(i)cellular uptake and availability of cholesterol
(ii) rate of conversion of cholesterol to pregnenolone (rate limiting step)
Carrier proteins 1- (3)
-increase amount transported in blood
-provide a reservoir of hormone
-extend half-life of the hormone in the circulation (contributing to a long duration of action)
Important carrier proteins include- specific (3)
cortisol-binding globulin (CBG) – binds cortisol in a selective manner (also some aldosterone)
thyroxine-binding globulin (TBG) – binds thyroxine (T4) selectively [also some triiodothyronine (T3)]
sex steroid-binding globulin (SSBG) – binds mainly testosterone and oestradiol
Important carrier proteins include- general (2)
albumin – binds many steroids and thyroxine
transthyretin – binds thyroxine and some steroids
Carrier proteins 2- (4)
a buffer and reservoir that helps to maintain relatively constant concentrations of free lipophilic hormone in the blood – free and bound hormone are in equilibrium
only free hormone can cross the capillary wall to activate receptors in target tissues (i.e. the biophase)
surges in hormone secretion are buffered by binding to carriers – free concentration does not rise abruptly
free hormone removed from plasma by elimination is replaced by bound hormone dissociating from carrier protein
HPA axis is the classic example control hormonal levels (6)
- Hypothalamus
- secretes corticotrophin releasing factor (CRF)
- anterior Pituitary
- secretes adrenocorticotrophic hormone (ACTH)
- Adrenal cortex
- secretes cortisol
Rate of elimination contributes to plasma concentration (7)
elimination occurs by several routes, but generally metabolism locally, by the liver and excretion by the kidney are most important
plasma concentration of hormone = rate of secretion – rate of elimination)
-amines e.g. adrenaline - t½ ~ seconds
-proteins and peptides - t½ ~ minutes
-steroids and thyroid hormones - t½ ~ hours to days due to extensive protein binding that suppresses elimination
hormone receptors - cell surface receptors (3)
ligand is hydrophillic
G-protein coupled (GPCR) – activated by amines and some proteins/peptides. Major signalling pathways involve coupling to Gs, Gi, or Gq
Receptor kinases – activated by some proteins/peptides
hormone receptors- Intracellular receptors (5)
ligand is lipophillic
Nuclear receptors – that can subdivided into class 1, class 2 and a hybrid class
class 1 - activated by many steroid hormones – in the absence of activating ligand these are mainly located in the cytoplasm bound to inhibitory heat shock proteins HSP) – move to the nucleus when activated
class 2 - activated mostly by lipids – constitutively present in the nucleus
hybrid class – activated by thyroid hormone (T3) and other substances – similar in function to class 1
Peptide Hormone Structure (Insulin) (4)
- Mature mRNA is translated into preproinsulin containing a ‘leader’ sequence followed by A, B and C domains.
- The leader sequence is cleaved in the ER lumen resulting in proinsulin.
- Proteases cleave the proinsulin at 2 sites removing the C peptide. The A and B chains remain connected by disulfide bonds.
- Mature insulin is stored in secretory vesicles until released following a signalling response. Release by exocytosis is dependent upon increasing intracellular Ca2+ concentrations.
Cellular Energy Status is Linked to Insulin Secretion in the Pancreatic B-cell
