Endocrynologie Flashcards
What is endocrinology?
- Coordination of physiological processes
ex: coorodinating mvt, respiration, circulation, digestion, excretion, metabolism all at once
endocrine system + CNS = major coordinating factors - Long distance communication
communicating between cells through chemical substances secreted by releasing cells and interact with specific receptors → specific physiological effects
What are the 2 type of signalling ?
Paracrine Signaling:
Very local, could be direct contact with target cell
Autocrine Signaling:
Cell releasing a hormone and has specific receptor on its surface (subcategory of paracrine but cell comunicates with itself)
What are the steps of hormone communication?
- Synthesis (of hormone by endocrine cell (or neutron in case of neurohormone)
- Release (of hormone …)
- Transport of hormone/neurhormone to target site by blood stream
- Detection of hormone/neurhormone by specific receptor protein on target cell
- Change in metabolism triggered by hormone
- Removal of the hormone (terminates the cellular response)
*Each step = potential source of signalling/response
How does the Hypothalamic-Pituitary signaling work?
Hypothalamic neurohormones released from hypothalamus (?) and inhibit/activates activity of 6 types of hormones-producing cells in the anterior pituitary
neurohormones are called releasing hormones/factors or inhibiting hormones/factor
What are the different classes of hormones and what are they base one?
Based on their structure
Glycoproteins (encoded by genes)
Polypeptides (encoded by genes)
Steroids (small molecules)
Amines (small molecules)
Ion Calcium (considered hormone bc calcium sensing receptors
How are hormones produced?
First produced as pre-hormones (synthesis on ribosomes)
prehormones → prohormones (Rough endoplasmic reticulum)
Hormones stored into vesicles with other peptides and are released from the cell
What are 4 important steroid hormones?
Cortisol
Aldosterone
Testosterone
Estradiol (Estrogene)
What is a unique feature of the Thyroid hormones?
They have Iodine in their structure
What are the properties of hormone receptors?
- Specificity: recognition of 1 single hormone/hormone family
- Affinity: Bonding hormone at its physiological concentration
- Should show saturability: finit # receptors
- Measureable biological effect: effect = response du to interaction of hormone with its receptor
What can be the issues in regulation of the receptors?
Upregulated → either by increasing their activity in response to hormone or their synthesis
Downregulated → either by decreasing their activity of their synthesis
What are the 3 mechanisms by which a hormone can exert effetc on a target cell?
- Direct effects on function at cell membrane
ex: insuline receptor activates glucose membrane carrier (to bring glucose into the cell) - intracellular effects mediated by second messenger systems
*First messenger = the hormone that binds to the receptor → ATP converted to cAMP - intracellular effects mediated by genomic of nuclear action
*Signaling by nuclear receptors including receptors for steroid hormones → steroid hormones have receptors inside the cytoplasm (not on cell surface), not at the surface and go into the nucleus to act on protein synthesis and alter functional response
By what mechanism is hormone secretion regulated?
Feedback mechanisms (negative most of the time, an excess of hormone leads to diminution of its sercretion)
How does the plasma Ca2+ regulation negative feeback loop work?
What organs are concerned by Ca2+?
Low plasma → ↑ stimulation of parathyroid gland → ↑ Synthesis/release of parathyroid hormone → ↑ PTH → Action on bond, kidney, gut → ↑ plasma Ca2+
Bond, kidney, gut!
*Negative feedback loop when Ca2+ plasma increases, decreases stimulation of parathyroid glands
What are the complete names of these acronymes ?
CRH
ACTH
CRH = corticotopin releasing hormone (secretion in hypothalamus)
ACTH = adrenocorticotopic hormone (secretion in anterior pituiraty gland)
cortisol (glucocorticoid) (secretion in adrenal cortex)
How does the regulation mechanism of stress work?
Stress or other inputs from other brain areas → INCREASE in CRH secretion (in Hypothalamus) → increase in plasma CRH → INCREASE in ACTH secretion (in anterior pituitary gland) → increase in plasma ACTH → INCREASE cortisol secretion (in adrenal cortex) → increase cortisol in plasma → target cell (of cortisol) responds to increase in cortisol
Résumé: CRH → ACTH → cortisol
Hypothalamus → anterior pituitary gland → adrenal cortex → target cell
*Negative feedback mechanism acts on hypothalamus secretion of CRH and anterior pituitary gland secretion of ACTH
What are the 2 parts of the pituitary gland?
Anterior pituitary gland → endocrine tissue
Posterior pituitary gland → neural tissue
Which important hormone is not encoded by genes?
Prolactin-inhibiting hormone
PIH, Dopamine
*but component necessary for dopamine synthesis are encoded by genes
What is the pathway of Oxytocin and Vasopressin?
Posterior Pituitary Gland does Neurohypohysis !!
Outgrowth of hypothalamus (connected to pituitary stalk)
Secretion of Oxytocin and Vasopressin (antidiuretic hormone - ADH)
Oxytocin and vasopressin synthesized in 2 hypothalamic nuclei (supra topic nucleus and paraventricular nucleus) *axons run down the pituitary stalk and terminate in posterior pituitary close to capillary blood vessels
*In axons, during transport, prohormones are processed in secretory granules (secretory granule travels the axon)
Mature hormone liberated from the Neurophysins I (for Oxytocin) and II (for vasopressin aka ADH)
Neurophysins = carrier molecules
ADH → Kidneys
Oxytocin → Uterus and Lactating mammary gland
*Circulating half-life of 1-3mins
What is the circulating half-time of oxytocin and vasopressin?
Why?
1-3 min to allow tight control
What are the roles of oxytocin ?
Females:
Parturition → uterus very sensitve to oxytocin at end of pregnancy, dilaiton uterine cervix causes oxytocin → uterine contraction
Milk ejection → response to stimulus of suckling, Causes milk filled ducts to contract and squeeze milk out
Behavioural effects → anxiety, enhances bonding, pro-social behaviour
Males:
Ejaculation → Oxytocin surge during sexual activity → epididimial passage of sperm and ejaculation
Behavioural effects → anxiety, enhances bonding, pro-social behaviour
What are characteristics of Colloid? Thyroglobulin? Thyroid Gland?
Colloid: major component = thyroglobulin, a large protein of 700,000 Da, Follicles in thyroid filled with colloid
Colloid contains thyroid hormone thyroxine (T4) and triiodothyronine (T3)
Thyroglobulin = protein your thyroid gland makes
Thyrglobulin = type of storage for T3, T4 before release
T3 and T4 are split off of it and enter blood where they bind to special plasma proteins
Synthesis of thyroglobulin under control of TSH of pituitary gland
Thyroid gland:
15 to 20 g (varies w/ diet, sex, etc.)
Larger in females than males
Only 3g of healthy thyroid needed to maintain euthyroid state (normal functional state)
What are the complete words for T3 and T4?
Thyroid hormone thyroxine
Triiodothyronine
What are the Tyroid hormones containing iodine (and their %?
What about the presence of iodine in the Thyroid hormones?
T4 = 90%
T3 = 9%
reverse T3 = 0.9%
-Availability of iodine limited in diet, etc.
- Cellular mechanisms developped for concentration, utilization of iodine in thyroid gland
- Thyroid follicular gland able to trap iodide and transport across the cell againsat chemical gradient (active transport)
How are the thyroid hormones synthesised?
- I- from plasma carried into thyroid follicular gland
- I- oxidized to Iodine (I2)
- I2 used of iodination of tyrosine residues of thyroglobulin (TGB) → forms monoiodotyrosine (MIT) + diiodotyrosine (DIT)
so I2 + TGB → MIT + DIT - Oxidative coupling of 2 DIT → Thyroxine (T4)
oxidative coupling of 1 MIT + 1 DIT → triiodothyronine (T3) - Hormones stored linked to thyroglobulin until go to plasma
*Rate of synthesis (all steps) ↑ by TSH
How is thyroid activity controlled?
TSH = thryoid stimulating hormone
interacts with specific receptors in follicular cells → increase production of T4 and T3
Without TSH, very low turnover of thyroid hormones
Synthesis + release of TSH controlled by hypothalamic TRH
TRH → TSH → specific receptors → increase in cAMP and Adenylyl cyclase → Thyroid hormones T3, T4
Negative feedback loop when T4 and T3 in blood increase at hypothalamic (TRH) and anterior pituitary (TSH) level
What are the complete names of TSH and TRH?
role in control of thyroid hormone release
TSH =Thyroid stimulating hormone
TRH = thyrotropin releasing hormone
What happens when there is iodine deficiency
Synthesis of thyroid hormones ↓ and T4 and T3 in circulation ↓
Release of TSH ↑ so thyroid folicular cells constantly stimulated
Thyroid enlarges (possibly → goiter)
Non-toxic goiter: bc enlarged, thyroid enable to synthesize biological active thyroid hormones due to the iodine deficiency,
What are the effects of Thyroid hormones?
Metabolism → increase CO, oxygenation of blood, rate of breathing, #RBC in circulation + carbs, lipids, proteins turnover
Growth → normal growth, stimulates growth hormone (GH) secretion
Neural development → neural branching, myelinization
What is the MOLECULAR mechanism of action of thyroid hormone? (on their target cells)
- Analogous to mechanism of action of steroid hormones: T3, T4 enter target cell nucleus → bind to their cognate nuclear receptor → alters transcription of specific genes → levels of encoded proteins
- Thyroid hormones may induce some effects by interactions with plasma membrane and mitochondria → specificT3/T4 receptor in mitochondiral membrane
- T3/T4 act directly at plasma membrane → increase uptake of amino acid (independent of protein synthesis) → linked with growth
What are the abnormalities of thyroid function?
Hypothyroidism → hypofunction of thyroid gland, low levels of thyroid hormones → weight gain, low metabolism
Hyperthyroidism → hyperfunction of thyroid gland, high levels of thyroid hormones → weight loss, higher body temp/heart rate, heat intolerance
*present at birth or occurs later in life
What is primary hypothyroidism? (Myxedema)
- At level of the thyroid
- inhability to synthesize active thyroid hormones
- More common in women than in man
- appears at about 40-60 years old
Causes:
1. Atrophy of thyroid (idiopathic atrophy = we don’t rlly know)
2. Autoimmune thyroiditis = Hashimoto’s disease = destruction by antibodies of cellular componenents of thyroid (more common in women) ( Hashimoto → genes recognize some part of thyroid as antigen)
3. Goitrous Hypothyroidism/Non-toxic Goitre = blockage in T3/T4 synthesis → Thyroid gland increases in size → goitre formation
What causes secondary hypothyroidism?
At the level of the pituitary
Synthesis of little/no TSH (Thyroid stimulating hormone)
What causes tertiary hypothyroidism?
At level of hypothalamus
Synthesis of little/no TRH (thyrotropin releasing hormone)
What causes infantile hypothyroidism?
- Absence of thyroid gland/ incomplete dev. (of thyroid gland) at birth
*fetus uses mother’s T3/T4, few months old, decrease in physical growth and mental dev.
Need early treatment bc can become irreversible
What is treatment for all types of Hypothyroidism?
Administration of thyroid hormones
What is primary hyperthyroidism?
At level of the thyroid gland
2 types:
- Toxic Diffuse Goiter (Graves Disease):
- Autoimmune disease characterized by presence of Long Acting Thyroid Stimulator (LATS) produced by Lymphocytes → it is an antibody that mimics TSH
- Constant stimulation by LATS increases mass of Thyroid → Toxic Goitre → bc synthesising biologically ACTIVE T4/T3 - Thyroid adenoma/thyroid cancer
- Synthesis of thyroid hormones independant of TSH
What causes secondary hyerthyroidism?
- level of anterior pituitary gland
- No negative feeback from increased levels of T3/T4 on the TSH
- Often due to PITUITARY TUMOR
What causes Tertiary Hyperthyroidism?
- At level of hypothalamus
- No negative feedback of high T3/T4 on synthesis of TRH
- often due to presence of HYPOTHALAMIC TUMOR
What are possible treatments for hyperthyroidism?
- Surgery + replacement therapy (administration of thyroid hormones)
- Administration of radioactive iodide (131I, 5mCi) → radioactive iodide concentrates in thyroid follicles → destroy them + replacement therapy if needed
- Administration of antithyroid drugs → propylthiouracil → blocks addition of iodine to thyroglobulin → careful not too much and cause hypothyroidism
