Endocrinology Flashcards
Why are hormones interesting?
Because hormones regulate many physiological and behavioural aspects, they are key mediaters of inner-tissue communication, and many diseases originate from dysregulation of hormones and their receptors.
How are hormones classified?
A substance that is produced in one tissue/organ and is released into the blood and carried to other organs, where it acts to produce a specific response
OBS, however the term is also often used to define chemical signals produced by cells affecting the same cell or near by cells
Describe the different kinds of endocrine signaling.
Autocrine: works on same cell
Paracrine: works on neighbouring cells
Endocrine: carried by blood to target cells far away
Intracrine: hormone works intracellularly (can both be producedin the same cell or not)
What are the seven classical endocrine glands?
Pituitary, thyroid, parathyroids, testes, ovary, adrenal, endocrine pancreas
What are the two other endocrine glands?
Pineal gland/body, thymus
What are the three hormone classes (chemical classification)?
Peptide-, amino acid-derived (amine)-, and steroid (cholestorol metabolites) hormones
Mention some peptide hormones.
Insulin, GH, TSH
Mention some amine hormones.
TH, dopamine, NE
Mention some steroid hormones.
Cortisol, estradiol, testosterone
What are the general rule about glandular cells and glands?
One glandular cell, one hormone (exceptions)
One gland, one or more hormones
What are some non-glandular endocrine tissues?
Liver, kidney, heart, skeletal muscle, adipose tissue, CNS, GIT and bone
What is a paraneoplastic syndrome?
Syndrome caused by cancer in the body, but not mediated by local cancer cells, but rather by hormones secreted by tumor cells or by an immuneresponse against a tumor
Which is most common, negative or positive feedback control?
Negative
Which are the two pathways for hormone secretion?
Constitutive: unregulated, vesicles filled with hormones and integral membrane proteins in trans part of golgi
Regulated: hormones stored in vesicles secreted upon stimulation, vesicles filled with hormones in cis part of golgi
How can hormones be transported?
Freely or bound to carrier proteins
What are the function of hormone binding proteins?
1) providing a reservoir of circulating hormones
2) restricting the “active” hormone level
3) extending the half-life or the hormone
4) delivering the hormone to target cells
What are some hormones that are both transported by hormone binding proteins and freely?
thyroid hormones, steroid hormones, IGF1+2, GH
What are some proteins that are freely transported in the blood?
Catecholamines, peptidehormones (except IGF1+2, GH)
What are the receptor types used for hormone signaling?
GPCRs, guanylyl cyclase receptors, RTKs, tyrosine kinase-associated receptors, and intracellular receptors (nuclear receptors)
Describe the signaling pathway mediated by guanylyl cyclase receptors, and the termination.
Signaling: Convert GTP –> cGMP –> cGMP activates PKG –> downstream signaling
Termination: PDEs degrade cGMP (PDE5 is a viagra target)
Describe the different G-proteins of GPCRs.
G_s + G_i: affecting AC activity
s = stimulating = [cAMP] increase
i = inhibiting = [cAMP] decrease
G_q: PLC activation = PIP2 –> IP3 + DAG –> [Ca2+] increase –> PKC activation
G_i + G_o: PLC_2 activation
Describe the signal transduction stimulated by RTKs.
Binding of ligand –> RTK autophosphorylation and phosphorylation of other RTK substrates.
Describe the signal transduction stimulated by tyrosine kinase-associated receptors.
Ligand binding –> bring JAKs in closer proximity –> JAKs crossphosphorylate each other and the receptor subunits –> activated JAKs phosphorylates downstream targets
Which receptor types do steroid and thyroid hormones bind to?
Intracellular receptors
Describe the properties posterior pituitary and the pathway of hormone secretion.
Hypothalamus lies above the pituitary glands.
No hormone producing cells.
Hormones are produced in the hypothalamus in large-bodied neurons of the paraventricular and supraoptic nuclei, and is transported through the pituitary stalk, and taken up by the capillary network from the posterior pituitary.
AVP (aka. ADH) and OT are released from here
Describe the properties anterior pituitary and the pathway of hormone secretion.
Hormones produced in small bodied-neurons of the hypothalamus –> released above the anterior pituitary in the median eminence –> taken up by the capillary network of the median eminence –> transported through the hypothalamo-hypophyseal portal vessles to AP –> stimulates hormone production in “troph” cells –> hormones picked up by the capillary network of AP
TSH, LH, and GH are produced in AP
–> stimulates hormone production elsewhere in the body
What does linear growth involve, and from where does it happen?
Lengthening of somatic tissue, e.g., bone, muscle, tendons, and skin
Happens from the epiphyseal (growth) plate, which closes at the end of puberty
Where are GH synthesized, stored, released from, controlled by, and what does it stimulate?
Synthesized in somatotrophs in AP, stored and released (regulated pathway) from AP, controlled by hypothalamus (positive and negative feedback), and it stimulates the liver production of IGF-1
Describe age-dependent effects of GH on growth.
GH must be present at early stage of life
What is acromegaly?
Disease caused by excess circulating GH after growth plate closure, usually due to benign pituitary adenoma, but can also be caused by a tumor
Phenotype: enlargement of hands, feet, nose, lips and ears, brow protrusion and tounge enlargement
Describe the secretory pathway of GH (positive regulation).
GHRH secreted from neurons in the arcuate nucleus (hypothalamus) –> stimulate GH production by somatothrops in AP and release of GH from AP
Describe how the GH secretion is negatively regulated by the hypothalamus.
Somatostatin secreted from neurons in the periventricular region –/ inhibits GH production and release
Which is more dominant, the positive or the negative regulation of GH secretion?
The positive
Describe the negative feedback mechanism of GH secretion.
1) GH secretion itself inhibits further production and secretion (somatotrophs)
2) IGF-1 inhibits production and secretion (somatotrophs)
3) IGF-1 stimulates somatosatin secretion (inhibits GH production and release)
4) IGF-1 inhibits GHRH secretion
How is GH secretion linked to the daily rythm?
Bursts of secretion during nighttime
Which receptor type does GH signal through?
Tyrosine kinase-associated receptor
How does GH promote linear growth?
Indirectly, as IGF-1/2 promotes linear growth
What are some key points about IGF?
High degree of simmilarity between IGF and proinsulin (C-peptide is not removed from IGF, + IGF contain a short D domain)
Most circulates bound to carriers
IGF-1 is much more dependent on GH than IGF-2
Which receptor types does IGF signal through?
RTKs.
When are human growth dependent on IGF-1?
Growth during puberty
How does GF effect metabolic properties?
Decrease glucose uptake, increase lipolysis and gluconeogenesis, and promotes insulin resistance
Which other hormones promote linear growth?
Thyroid hormone, sex steroids, glucocorticoids, insulin
What is a (rare) cause of obesity?
Leptin deficiency and deficiency in leptin receptor
What is leptin?
An appetite controler (appetite suppresion, increasing energy expenditure)
Which is the only visible gland common for both sexes?
The thyroid gland
Which hormones are the only ones that need an essential trace element for their synthesis?
Thyroid hormones, needs iodine
Where are thyroid hormones stored?
Extracellularly
Which receptor types does the thyroid hormones signal through?
Nuclear receptors
Where are the thyroid gland located, and what cells does it contain?
Around the trachea
Contains: follicular cells, parafollicular (C) cells, red blood cells. The follicular cells surrond the colloid
Describe the structure of thyroid hormones.
COOH-HCNH2-HCH-benzene + 1/2 iodine-O-benzene + 1/2 iodine-OH
T3: one iodine on the second benzene ring
rT3: one iodine on the first benzene ring
T4: 2xiodine on both benzene rings
Describe the synthesis of thyroid hormones.
- Follicular cells trap iodide (I-) from the blood
- The anion iodide exits the follicular cells through the pendrin and is released into the follicle lumen
- Follicular cells release vesicles containing Tg and TPO into the follicle lumen
- I- is oxidiced into iodine (I0) in the lumen by TPO
- Selected tyrosyl residues in Tg become iodinated
- An internal rearrangement of the iodinated Tg occurs, by which two iodinated tyrosyl residues become conjugated by en ether linkage catalyzed by TPO
- Follicular cells take up iodinated Tg by endocytosis
- The endocytic vesicles fuse with lysosomes, whereby iodinated Tg becomes hydrolyzed, releasing T3/T4 to the blood through the basolateral membrane by a not fulle characterized mechanism
What are the ratio of T3/T4 secreted?
App. 1:9
How much of the circulating T3 is made by deidodination of T4 in non-thyroidal tissue?
App. 75 %
How much of the circulating thyroid hormones are bound to carrier proteins, and which carrier proteins?
> 99.5 %, TBG and TTR
Which thyroid hormone is the most potent?
T3, app. 10 fold
What is T4 sometimes reffered to as?
A prohormone
How are T4 deiodinated to T3?
By iodothyronine deiodinases:
D1: targets both rings
D2: targets the outer ring
D3: targets the inner ring
What are the difference between D2 and D3 expressing cells?
D2: enhanced thyroid hormone signaling
D3: diminished thyroid hormone signaling
What are the general rule about thyroid hormone receptors (TRs)?
Unliganded TRs repress transcription of target genes through interactions with corepressor proteins
T3 binding to TR causes transcriptional activation of target genes through recruitment of coactivator proteins
OBS: exception to rule: binding of T3 to TR causes transcriptional repression
What does cold exposure stimulate in brown adipose tissue?
The deiodination of T4 –> T3 by D2
Local [T3] increase –> increased expression of thermogenic genes like UCP1
How is the metabolic rate affected by thyroid hormones?
Hypothyroid –> decreased basal metabolic rate + metabolism + protein/lipid metabolism , + thermogenesis
Hyperthyroid –> vice versa
What can prolonged hyperthyroid state lead to?
Graves disease
Nervousness, anxiety, irritability etc.
How does thyroid hormone deficiency during growth and development affect the patient?
Reduced height, bone growth, and mental age.
Replacement therapy can help with growth and height, but not mental age. To help the mental capacity, treatment must be initiated within days of birth.
Describe the thyroid hormone secreting pathway.
Neurons in hypothalamus secrete TRH –> thyrotrophs in AP secrete THS (thyrotropin) –> follicular cells in TG secrete T3/T4
Describe the thyroid hormone secreting pathway.
Neurons in hypothalamus secrete TRH –> thyrotrophs in AP secrete THS (thyrotropin) –> follicular cells in TG secrete T3/T4
Describe the negative feedback mechanism of T3/T4 release.
T3/T4 inhibits neurons in hypothalamus (release of TRH), and inhibits AP release of THS
What diseases can iodine deficiency lead to?
Goiter: caused by iodine deficiency later in life –> TSH release increased ad a compensatory mechanism –> enlarged thyroid gland as TSH promotes proliferation of follicular cells in TG
Critinism: caused by iodine deficiency during early life –> defective CNS development –> mental retardation
What diseases can hypothyroidism lead to?
Hashimoto thyroiditis: Autoimmune disease - anti-thyroid antibodies target follicular cells –> blockage/destruction of TG
Myxedema coma: Development of hypothermia and coma (rare condition in elderly patients)
What diseases can hyperthyroidism lead to?
Grave’s disease: autoimmune disease - anti-TSH receptor antibodies causing chronic TSH R activation –> boost most aspects of TH synthesis and secretion –> thyroid hyperplasia
What part of the pancreas covers the endocrine pancreas?
Islet of Langerhans with alpha-, beta-, delta- and F cells
What does the different cells in the Islet of Langerhans produce?
Alpha: glucagon
Beta: insulin
Delta: somatostatin
F: pancreatic polypeptide
Pancreas is innervated by para- and sympaticus. How does this two system affect the hormone secretion?
Para: increase insulin, small glucagon increase, PP increase
Sym: decrease insulin, increase glucagon and vasoconstriction
What else influences pancreatic hormone secretion?
A de-centralized system through glucose sensing
What else influences pancreatic hormone secretion?
A de-centralized system through glucose sensing
What are insulin involved in?
Glucose storage and oxidation (increase), protein synthesis (increase), and proteolysis (decrease)
Also activates glucose metabolism, glucogen synthesis and lipogenesis
What are glucagon involved in?
Signal to liver –> stimulates gluconeogenesis (glucogen –> glucose) by regulating the enzymes involved in this process
Also reduces the feeling of huger, increase ketone body production, and AA/lipid/glucose in liver breakdown
How is the endocrine pancreas a part of why we are such a succesful species?
Because it facillitates an adaptive system for fasting and feeding
Which of insulin/glucagon is an anabolic (feeding state) hormone and which is a catabolic (fasting state) hormone?
Insulin: anabolic
Glucagon: catabolic
True or flase? In diabetes both insulin, glucagon and somatostatin become dysregulated?
True
