Hypothalamus and Pitutary Flashcards
1
Q
Pitutary function is regulated by —– produced in the —–
A
- neurohormones
- hypothalamus (neuronal system)
2
Q
In hypothalamus there are many clusters of neurons known as (3):
+ such as + what they do
A
- Hypothalamic nuclei
- Such as Supraoptic, paraventricular, preoptic nuclei
- They are clusters of neurosecretory neurons that produce hormones that control pitutary function
3
Q
The anterior pitutary, posterior pituitary, intermediate lobe derivation (3):
A
- AP: Embryologically derived from dorsal outgrowth of the buccal cavity (roof of the mouth) cells come from non-neurological origin from epithelia cell
- PP: Embryologically derived from the brain (outgrowth from the brain)
- IL: Region in between anterior and posterior pituitary associated with adenohypophysis. Not present in some mammals, birds, hagfish and lamprey
4
Q
Adenohypophysis contains (3):
A
- Pars tuberalis (tuberal lobe)
- Pars intermedia (intermediate lobe)
- Pars distalis (anterior lobe)
5
Q
Neurohypophysis (2)
A
- Infundibulum (neural lobe)
- Pars Nervosa (neural lobe/posterior putuitary)
6
Q
Neurophypophysis hormone synthesis (2):
A
- Secretory cells that produce hormones secreted from PP is synthesized in hypothalamus (supraoptic + paraventricular) and travel down axon (hypothalamic-posterior pituitary stalk)and terminate in neural lobe. The hormones remain in terminal nerve until stimulated then it is secreted in blood vessels in PP.
- There are no secretatory cells in the posterior lobe
7
Q
Adenohypophysis hormone synthesis (4):
+detection
A
- All hormones are produced and secreted in anterior pitutary
- Neurohormones are produced by hypothalamus and terminates at median eminenance above the AP. It then enter protal system (hypothalamic-hypophyseal portal system)
- Release of hormone in the anterior pitutary and these hormone target tissue that are cells in anterior pituitary to release hormones.
- Neurohormones released by hypothalamus cannot be detected in bood but the anterior pituitary hormones released by target cells in anterior pituitary are released in blood.
8
Q
Hormones of posterior pituitary (4):
+ details/structure
A
- Vassopressin (AVP, Arginine vassopressin; Arg at position 8)
- Oxytocin (OX)
- Each contains 9 amino acids ( 9 diff ones but 2 of cys) and is a nano-peptide
- 2 cys forms di-sulfide bonds making them cyclic and also the cyclic structure allows it to stabilize conformation of the hormones to activate receptors
9
Q
Hormones of posterior pituitary
There are other structurally different neurohypophysial hormones found within mammalian and nonmammalian vertebrates:
A
Due to evolution. 8-9 variation of peptide in species
10
Q
Synthesis of Vasopressin (ADH) and oxytocin (3):
what + signal + neurons
A
- They are synthesized within the cell bodies of the neurons located in the supraoptic and paraventricular nuclei (DNA synthesis occurs, precursor are cleaved to nanopeptide) of the hypothalamus and then transported to terminals in the posterior pituitary.
- When signals come, 2 things happen:
1. Stimulate of instant release of hormones to blood
2. Stimulate neuralsecretatory cells to start protein synthesis - The neurons either produce oxytocin or vasopression, neither are in the same neuron. Control of secretion are different: secretion of oxytocin has no effect on vasopressin.
11
Q
Arginine vasopressin (AVP) is also known as:
A
Antidiuretic hormone (ADH)
12
Q
Effects of AVP
AVP acts through 2 types of membrane receptors (2):
A
V1: The V1 receptor mediates vascular smooth muscle contraction such as blood vessels (increases blood pressure)
V2: The V2 receptors produces the renal action of AVP (AVP increases water reabsorption and you pee less when AVP increases)
13
Q
AVP also acts to facilitate:
A
- Memory consolidation
- AVP treatment improves short- term memory in aged humans
14
Q
AVP is a neuron endocrine and also acts as a:
A
neurocrine (neurotransmitter)
15
Q
AVP secretion are affected by 2 factors:
A
- Blood pressure
Baroroeceptors controls production of the hormone by detection in blood pressure changes.
Decreased blood pressure -> activation of baroreceptors-> increase AVP secretion -> results in increase water updatke (V2); constriction of arterioles (V1)-> Increase blood pressure
- Water retenstion
The amount of salt (NA+ concentration in circulation) allows osmoreceptors to detect and control AVP.
Increased blood osmolality/ Na+ (eat lots of salt) -> activation of osmoreceptors in CNS-> increased AVP secrection -> increased water retention (V2)/Na+ secrection (V2) ->Increase in urine concentration/urine osmolality and decrease in urine volue
16
Q
Relationship between plasma AVP, plasma osmolality and plasma AVP:
A
Increase plasma osmolality means more plasma AVP (more AVP released) and more plasma AVP means more urine osmolality because all the water is being reabsorbed and the urine is highly concentrated.
17
Q
Change in blood pressure and production of AVP has a —- relationship
A
- direct
18
Q
When AVP goes down, there is a —- in blood pressure
A
decrease
19
Q
The AVP response to plasma osmolality is very:
A
sensitive (1% change activates AVP release)
20
Q
Summary of the regulation of AVP release:
Simulation
A
21
Q
Summary of the regulation of AVP release:
Inhibition
A
- cold weather pee more
22
Q
What does oxytocin do in terms of milk? (2)
What + how
A
- It stimulates milk ejection by contacting the myoepithelial cells in the mammary gland (smooth muscles)
- Suckling stimulates sensory nerves in the areolae and nipples of the breast (Sends signal to brain causeing afferent bervous pathway). This causes increase in firing of neurons and stimulates part of the brain that sends signal to secretory cells in hypothalamus (supraoptic + para) which produce oxytocin directly and start secreting
milk secretion not production
23
Q
Effect of oxytocin is most …
A
- prominent after parturition because hormones involved in pregnancy and parturition increase in receptor density in nipples
24
Q
What does oxytocin do in terms of parturition? (2)
+ cycle
A
- ## Oxytocin stimulates contraction of myometrium (smooth muscle) which facilitates labor. It does not initiate labour bur produces more and more so that it is important for birth
25
Hypothalamus, pituitary and target cell relationship diagram:
26
Anterior Lobe contains a variety of cell types which secrete hormones (5):
27
WHat are the 3 different familes of peptide hormones of Adenohypophysis:
1. Family 1: Growth hormones (GH) and prolactin (PRL) *Produced in Ant Pit*
2. Family 2: Glycoprotein Hormones *Produced in Ant Pit*
3. Family 3: Hormones derived from Pro-opiomelanocortin (POMC) *Produced in Ant Pit and Int lobe*
28
# Peptide hormones of Adenohypophysis
Family I (2)
| Includes + structure
- Includes somatotropin or Growth Hormones (GH) and prolactin (PRL)
- Both GH and PRL consist of approximately 200 amino acids (single chain protein/linear) as they have same ancestor gene
29
# Peptide hormones of Adenohypophysis
Family II (2)
| The types + **produced**
Glycoproteins hormones that include:
1. **Thyroid stimulating Hormone (TSH)**
2. **Gonadotropin Hormones**
- Follicle-stimulating hormone (FSH) *Produced in Ant Pit*
- Luteinizing hormone (LH) *Produced in Ant Pit*
- Chorionic gonadotropin (Produced in placenta, the chrion; LH-like)
30
# Peptide hormones of Adenohypophysis
Family II (4)
| Structure
- Each is composed of two subunits; alpha and beta (noncovalently linked) and does not have strong association
- Seperated subunits have no biological activity (needs to be associated)
- The alpha subunit is the same for all glycoprotein hormones (TSH, LH, FSH)
- The B- subunit are different - confer special functional property
31
Chorionic gonadotropin (2)
| produce + measure
- Present only in pregnancy as it is produced in placenta by chrion
- You measure this on pregnancy test
32
# Peptide hormones of Adenohypophysis
Family 3 (5)
| Includes + all have + where they are produced
- Hormones derived from Pro-opipmelanocortin (POMC) includes:
1. Adrenocorticotropin Hormone (ACTH) **Produced in Anti Pit**
2. Melanocyte-stimulating hormone (a-MSH, B- MSH) *Target skin pigmentation* **Produced in Intermediate Lobe**
3. B- endorphin *endogenous opioid* **Produced in Intermediate Lobe**
4. B-Lipotropic hormone (B-LPH) *Important for lipid metabolism* **Produced in Intermediate Lobe**
**They all have the same precursor in different cells**
33
Where is a-MSH produced?
Intermediate lobe
| Some exceptions in Anterior Pituitary
34
Endogenous opioid
Endogenous opioids are peptide hormones produced in the neuron system and involved in various physiological processes such as pain regulation
35
How are hormones derived from Pro-opiomelanocortin (POMC) precursors?
- POMC gene is expressed in different cell types producing ACTH, MSH, B-endorphin and B-LPH *Gene is in all the different cell type and can produce all these hormones*
- POMC derived peptides are cleaved specifically by a family of prohormone convertase expressed diferentially in various cell types *Cleave precursor in different places*
36
a-MSH (3)
| structure + secreted + what it does
- a 13 amino acid peptide derived from the precursor POMC
- Secreted from melanotropes in pars intermedia or intermediate lobe
- a-MSH acts on melanocytes and stimulates dispersion of melanin granules within these cells, resulting in darkening of the skin (dispersed = skin darker = more melanin present)
37
Intermediate lobe/ Pars intermedia
Infants do have intermediate lobe in humans and in age 2-3 they start to disappear by fusing with posterior pituitary and everything produced in intermediate lobe in adult human moves into anterior pituitary.
Adult humans, whale, dophins and birds do not have intermediate lobes.
38
Animals that camoflage appear to
have large intermediate lobe
39
Prolactin (2)
| Unique + specialize
- Only pituitary hormone where we do not have a strong stimulator
- Prolactin appears to not specialize early in vertebrate evolution and instead is used by different species to control a wide variety of functions such as reproduction, osmoregulation, growth and development *Many of these effects are species-specific*
40
Factors effecting PRL release from pituitary (2):
- Dopamine (DA): Strong inhibitor
Main controller for prolactin production by secreting inhibitory hormone. Dopaminergic input in pituitary inhibits the production of prolactin
- Cholecytokinin (CCK)
Reduce dopaminergic secretion in pituitary so prolactin levels go up. Weak stimulator
41
# Reproductive actions of prolactin:
Prolactin in male (2)
- Increase and maintain LH receptors in testis (LH helps signal the testicles to make testosterone)
- Increase sperm motility by stimulating Ca2+ in testis
42
# Reproductive actions of prolactin:
Prolactin in females (5)
- Prolactin stimulates lactation: It stimulates synthesis of casein (a major milk protein) and fatty acids in milk
- Increases progesterone synthesis (reproduction in females)
- Prolactin stimulates the migration of IgA lymphoblasts (antibody) to the mammary gland (passed on during nursing to provide passive immunity)
- Prolactin has an osmoregulatory function in the uterus (aminotic fluid, baby doesnt shrink/swell)
- High prolactin level observed during lactation reduces gonadotropin production (inhibits LH to reduce pregancy while nursing), suppress sexual activity.
43
Growth hormone are also known as ---- as they -----
- somatotropin
- stimulate somatic growth
44
The main action of GH is:
The stimulation of somatic growth (skeletal and soft tissues)
45
GH exerts it action both:
Directly at the target cell or indirectly through production of growth factors (e.g., IGF-I and IGF-II)
46
GHRH (44aa) (2)
- Released on median emmince portal system in anterior pituitary. It acts on somatotropes to release/syntheize GH.
- Main stimulation of GH produced in hypothalamas
47
Somatostatin (~28 aa)
Peptide that prevents production of GH
48
IGF-I and GH
- GH produced act on a number of target tissue and in the liver which is the main site of IGF production
- IGF-1 that is synthesized in the liver and secreted into the blood is under the control of GH. It causes negative feedback at brain/pituitary to maintain constant GH level.
49
GH and Hypoglycemia
Low blood sugar causes higher GH
50
High protein meal ---- GH
stimulates
51
Fatty acids and GH
GH needs energy in addition to producing IGF. Lipids and fat undergo lipolysis to release fatty acids. High fat levels provide negative feedback.
GH promotes lipolysis, the breakdown of stored triglycerides in adipose tissue, to release free fatty acids (FFAs) and glycerol into the bloodstream. These FFAs serve as an energy source for many tissues, particularly during fasting or energy-demanding periods.
Negative Feedback from High Fat Levels: Elevated levels of circulating FFAs can exert negative feedback on GH secretion. This mechanism likely helps maintain balance, preventing excessive breakdown of fat and conserving energy stores.
52
Physiological actions of GH (2)
53
GH/Growth rate and age
54
Too much GH before puberty can cause:
Gigantism
- produces disproportionately long arms and legs
| Usually pituitary tumor that cause very tall abnormal arm and leg length
55
Too much GH produced after puberty can cause (3):
| What/why + symptoms + treatment
Acromegaly deformatities
There is no linear growth. The epiphyseal plate is a thin layer of cartilage located at the ends of long bones. It's responsible for producing new cartilage cells (chondrocytes), which later ossify (turn into bone), leading to linear growth during childhood and adolescence. As a person reaches late adolescence or early adulthood, hormonal changes (particularly the rise in estrogen) lead to the ossification of the epiphyseal cartilage. When the cartilage is fully replaced by bone, the growth plates "fuse," and no further longitudinal bone growth is possible. During this process, the chondrocytes (cartilage-producing cells) stop dividing and are gradually replaced by bone tissue. This marks the end of linear growth.
- Enlargment of skull, facial bones, jaw, hands, feet, soft tissue and organs, diabetes, hypertension, muscle weakness, arthritis, gonadal dysfunction, cardiovascular disease.
- Treatment: Tumor removal (usually caused by Pit. tumor) or somatostatin analogs
56
Too Little GH can cause:
Dwarfism
57
Two result of GH deficiency (2)
- Dwarfism if occurs early in life
- If occur in adults can cause weakness, fine wrinkling and pale skin, loss of sex drive, genital atrophy, menstrual cycle cessation
| You cannot correct this after puberty
58
GH receptor deficiency (5)
| cause + what + cannot correct with +correct with + puberty
- A rare condition causing dwarfism
- Genectic disorder
- Cannot correct with more GH
- Crisper Cas 9/Gene therapy to correct deficiency
- Correcting after puberty has no affect
59
Thyroid hormones and normal growth function (3):
| Relationship + 2 examples
Thyroid hormones are not a growth hormone by itself however, there is a synergism (the interaction or cooperation of two or more organizations, substances, or other agents to produce a combined effect) between the two.
- Hypophysectomy (removal of pituitary gland) totally abolishes the growth
- Low thyroid level in children or young animals leads to abnormal growth and development
60
61
Describe the graph of hypothyroidism and height:
62
Thyroid hormone production (2)
- Thyroid hormones are produced in thyroid follicules that are lined with secretatory cells. The inside is filled with a fluid called "colloid"
- There are also blood vessels that take away secreted thyroid hormones produced by the cell
63
Thyroid Stimulating hormone (TSH) (3)
| structure + produced/what
- A glycoprotein consisting of two subunits, a and b
- a-subunit contains 89 amino acid, B-subunit contains 112 amino acids
- Produced in the anterior pituitary and controls thyroid hormone production
64
Factors effecting TSH release (2):
2: What
| 1: what + produced where +size + cannot be
**TRH (Glu-His-Pro-NH2): **
- Stimulator of TSH
- Produced in hypothalamus nuclei by supraoptic, paraventicular and goes to anterior pituitary to release TSH. TSH then go in blood and act on thyroid secreting cells (follicles) to release thyroid hormones
- Smallest peptide hormone (3 peptide)
- Cannot be measured in the blood, levels are low, function only to control levels of TSH in anterior pituitary.
** T3, T4:** Increased thyroid hormone levels inhibit (negative feedback) TSH
65
Thyroid stimulating hormone stimulates ----- synthesis in -----
- thyroglobulin (Tg)/ Thyroid hormone: Triiodothyronine T3/ Tetraiodothyronine T4
- follicular cells
66
Chronic increase in TSH leads to (2):
| What + causes...bc
- Hypertrophy (increase in size of the cell) and hyperplasia (increase in number/division of cells) of thyroid follicles
- Causes tumor like structure in thyroid: too much TSH mostly due to thyroid hormone being deficient for - feedback
67
Goiter (2)
| TH + TSH + cell
- Occurs with low T3, T4 and high TSH
- Increase in hyperplasia and hypertrophy
68
Edemic goiter (2)
| Due to...
- Due to iodine deficiency (important for synthesis of thyroid hormone) causing decreased synthesis of T3 and T4
- Increased TSH causes enlargemnet (hyperplasia) of the gland
69
Thyroid hormones synthesis from scratch (11):
1. Supraoptic, paraventicular stimulates release of TRH from hypothalamus to thyrotrope cells in anterior pituitary.
2. Thyrotrope cells produce TSH which travels in bloodstream and binds to receptor in thyroid follicule cells.
3. This activates a G-protein that activates anylcyclase to convert ATP to CAMP
4. CAMP activates Protein kinase A which phosphorylates transcription factors allowing the transcription/translation of thyrogobulin
5. Thyrogobulin has tyrosine attached as residues
6. Iodide is present in bloodstream as I-. Active transport stimulated by TSH. TSH acts on membrane associated receptors: G-protein and increase CAMP and PK which phosphorylates transporter molecules increasing iodide transport I-. Coupled with Na+ to cross into thryoid follicules.
7. Iodide oxidation.
Pentosephosphate pathway is mediated by perioxidase which produces hydrogen peroxide. H2O2 is the most potent oxidizing agent and causes oxidation of iodide I- molecule into iodine I2. Release into Lumen.
8. Inodination of tyrosyl residue:
I- Is a free radical so it can form reaction and attach to tyrosine residue to make monoiodothyronine or diiodothyronine in lumen.
10. Thyrogobulin colloid gets endocytosed intp follicular cell and lysosome fuses with the vesicles and cuts: two diiodothyronine detach from thyrogobulin and form oxidative coupling. They bind together and become 2 tyrosine residues (T4). A monoiodothyronine and diiodothyronine forms T3. We have isolated T3 and T4 from thyrogobulin colloid via lysosomal enzymes.
11. T4 and T3 fuse with secretatory cell membrane and gets released to bloodstream via exocytosis. Lone iodotyrosines get deiodinased into iodide and recycled.
70
T3 vs T4 (5)
| Diff + longetivity + relation + normal condions
- T3 has a higher affinity for receptor due to it's conformation and is the main ligand/ active hormone in metabolic regulation like growth.
- T3 is destroyed quickly
- T4 is the precursor to T3
- T4 has Longer half-life
- T4 is produced under normal conditions because you have enough iodide being ingested. Enough iodide means more dioidothyronine and defiency in iodide means more monoiodothyronine.
71
Synthesis of thyroid hormones summarized in 4 steps:
1. Iodide trapping by active transport mechanism
2. Oxidation: Iodide (I-) is oxidized to iodine (I2) mediated by iodide peroxidase and H2O2
3. Iodination of tyrosyl residues of thyrogobulin molecules (~ 600,000) to form MIT and DIT
4. Oxidative coupling of tyrosine causes formation of mostly tetraiodothyronine (T4) and smaller amounts of T3 stored in colloid space
72
Coupling of DIT- DIT:
T4
73
Coupling of DIT-MIT:
T3
74
How is T3 produced from T4?
Most of T3 is produced from deiodination of T4 mediated by deiodinases in the tissues outside of the thyroid gland including liver, kidneys and brown fat.
75
Function of thyroid hormones: Metamorphosis (3)
| What + Ex
- Thyroid hormones stimulate metamorphosis in amphibian larvae
- Thyroidectomized tadpoles remain as tadpoles (Chemical that prevents thyroid hormones prevents metamorphosis)
- Treatment with the tyroid hormone reverses this effect (lose gill, develope lungs)
76
Function of thyroid hormones: Growth (3)
| birds/mammals + rats + humans
- In birds and mammals, thyroidectomy results in growth retardation
- Thyroidectomy in new born rats (abnormality due to hypothyrodism) results in bone malformation of skull, delayed ossification (cartilaginous tissue transform to bone) of long bones
- Thyroid hormone therapy begining before 15 days of age in humans corrects these abnormalities. After this age, hormone treatment is relatively ineffective (mentally handicapped).
77
Thyroid hormones and teeth:
Growth and eruption of teeth are influenced and controlled by thyroid hormones. In hypothyroid children, the eruption of permanent teeth is greatly delayed.
78
Thyroid hormones and nervous system:
Thyroidectomy in young rats or treatment with anti-thyroid drugs results in smaller than normal brain, reduction of the number of axons in the cerebral cortex.
| decrease cognition
79
Congential hypothyroidism if not treated can cause mental retardation, treatment includes (3):
| + time frame
- Thyroid replacement
- If begun prior to 6 weeks potential for normal IQ
- If delayed to 6 months average IQ is 55
| **Cannot be reversed**
80
Metabolic functions and thyroid hormones (2):
| maintain + in birds and mammals
- Thyroid hormones maintain BMR (can be measured by O2 level)
- In birds and mammals (endothermic= maintain constant temp) thyroid increases O2 consumption and heat production (calorgenesis)
81
Metabolic effect for mammals in prolonged cold:
82
Thyroid hormones at physiological concentrations increase (3) ....
and favours (1)
- protein synthesis, growth rate and results in positive nitrogen balance meaning you retain nitrogen more than excreting it
- It also favours lipolysis and raising of free fatty acid in the blood inorder to mobilize energy for use in metabolism
## Footnote
Nitrogen balance is the difference between the amount of nitrogen a person consumes and the amount they excrete. It's a key indicator of protein metabolism and is important for growth, metabolic stability, and physical decline. Positive NB means there is an increase in total body protein. This is the normal state in growth (including pregnancy), and in an adult recoveing from a loss of body protein in response to trauma or undernutrition.
83
Anabolic
| What
Inhance growth
building
84
Catabolic (2)
| What/increase + NB
- Breakdown of protein (increase proteolosis)
- Negative nitrogen balance, youe excrete more than take in
## Footnote
Nitrogen balance is the difference between the amount of nitrogen a person consumes and the amount they excrete. It's a key indicator of protein metabolism and is important for growth, metabolic stability, and physical decline. Negative NB means there is a nett loss of body protein. This is never normal, but reflects either a response to trauma or infection, or an intake that is inadequate to meet the need to replace tissue proteins that are turning over.
