Endocrine Systems & Receptors

Question 1

Hypothalamus + pituitary gland are secreted by

Answer 1

Peptide

Question 2

thyroid + parathyroid glands are secreted by

Answer 2

Peptide and amine hormone secretion

Question 3

adrenal glands are secreted by

Answer 3

Steroid and amine secretion

Question 4

pancreas secreted by

Answer 4

peptide

Question 5

ovaries + testes are secreted by

Answer 5

steriod

Question 6

The Endocrine System

Answer 6

Classically consists of ductless endocrine glands
(c.f. exocrine glands)

Question 7

The Endocrine System- communication

Answer 7

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

Question 8

The Endocrine System- signalling (3)

Answer 8

Specificity of signalling is achieved by:

(i) chemically distinct hormones

(ii) specific receptors for each hormone

(iii) distinct distribution of receptors across target cells

Question 9

Examples of chemical signalling (3)

Answer 9

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

Question 10

Hormone Synthesis, Storage, Release and Transport 1-(4)

Answer 10

Amines:
-are hydrophilic+ are transported mainly ‘free’ in plasma
-pre-synthesised, stored in vesicles
-released in response to stimuli by Ca2+-dependent exocytosis

Question 11

Hormone Synthesis, Storage, Release and Transport 2- (4)

Answer 11

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

Question 12

Hormone Synthesis, Storage, Release and Transport
3- (7)

Answer 12

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)

Question 13

Carrier proteins 1- (3)

Answer 13

-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)

Question 14

Important carrier proteins include- specific (3)

Answer 14

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

Question 15

Important carrier proteins include- general (2)

Answer 15

albumin – binds many steroids and thyroxine

transthyretin – binds thyroxine and some steroids

Question 16

Carrier proteins 2- (4)

Answer 16

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

Question 17

HPA axis is the classic example control hormonal levels (6)

Answer 17

1. Hypothalamus
2. secretes corticotrophin releasing factor (CRF)
3. anterior Pituitary
4. secretes adrenocorticotrophic hormone (ACTH)
5. Adrenal cortex
6. secretes cortisol

Question 18

Rate of elimination contributes to plasma concentration (7)

Answer 18

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

Question 19

hormone receptors - cell surface receptors (3)

Answer 19

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

Question 20

hormone receptors- Intracellular receptors (5)

Answer 20

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

Question 21

Peptide Hormone Structure (Insulin) (4)

Answer 21

1. Mature mRNA is translated into preproinsulin containing a ‘leader’ sequence followed by A, B and C domains.
2. The leader sequence is cleaved in the ER lumen resulting in proinsulin.
3. Proteases cleave the proinsulin at 2 sites removing the C peptide. The A and B chains remain connected by disulfide bonds.
4. Mature insulin is stored in secretory vesicles until released following a signalling response. Release by exocytosis is dependent upon increasing intracellular Ca2+ concentrations.

Question 22

Cellular Energy Status is Linked to Insulin Secretion in the Pancreatic B-cell