Ch 11: Endocrine System

Ch 11: Endocrine System

Ch 11: Endocrine System SLOs Describe the chemical nature of hormones and define the terms pro- and preprohormone. Explain mechanism of action of steroid and thyroid hormones Create chart to distinguish the the different classes of hormones (steroids, amines, poly peptides, and proteins and glycoproteins) according to how they are synthesized, stored, released, transported in blood, and cellular mechanisms of action. Predict the classification of an unknown hormone from knowledge of its synthesis, storage and release, transport in the blood, and cellular mechanism of action. Differentiate between anterior pituitary and posterior pituitary. List (full spellings and abbreviations) the hormones secreted by the anterior and posterior pituitary and identify the ones that have trophic effects.

Explain how the hypothalamus regulates the anterior and posterior pituitary glands. Describe negative feedback inhibition in the regulation of hypothalamic and anterior pituitary hormones Diagnose primary and secondary endocrine pathologies Review endocrine pathologies of Cushings disease, Gigantism, Graves disease, endemic goiter, Hashimotos thyroiditis. Apply knowledge of feedback loops and hormone hyper/hyposecretion, and abnormal tissue responsiveness. Endocrine Glands and Hormones Review anatomy of ES / Major endocrine glands? What is a hormone? What is a neurohormone? __________________: Study of hormones, their receptors, intracellular signaling pathways they invoke, diseases

and conditions associated with them. Compare to Fig 11-1 Physiological processes controlled by hormones? Chemical Classification of Hormones 3 main types: Steroids derived from __________ __________, __________, __________, __________ Secreted by __________ and __________ Amines, derived from tyrosine and tryptophan _____________________, T3 and T4, melatonin Polypeptides, Proteins and Glycoproteins ADH, insulin, GH, FSH and LH

Where synthesized? Lipophilic or phobic? Where stored? How transported in blood? Different classes of hormones differ on basis of synthesis, storage, release, transport and cellular mechanism of action Polar vs. non-polar Lipo______ vs. lipo______ Biosynthetic Pathway for Steroid Hormones All derived from _______________ C A D Spermatic

cord B HO C O C O O Androstenedione Testosterone

? Progesterone na re ad Ovary C ls HO

Corpus luteum O OH Estradiol-17 O ? OH Ovary

Cortisol (hydrocortisone) ? Adrenal cortex Fig 11-2 ov ar ie s HO

CH2OH In ? In In O O te st

es CH3 Pregnenolone Testis Seminiferous tubules CH3 HO OH

O Cholesterol Interstitial (Leydig) cells Follicles in ovary Tyrosine Derivatives I I

I I I I I Compare to Fig 7-6 Pro-, Pre-, and Preprohormones Some hormones are 1st produced as precursor molecules. They must be

cut and sometimes spliced together to be active. E.g.: Insulin Common Aspects of Neural & Endocrine Regulation Many similarities: Hormones and NTs both interact with specific _________ Leads to change within cell Signal molecule is either removed or inactivated Multiple hormones can affect a single target simultaneously Three types of hormone interactions: Synergism Permissiveness

Antagonism Synergism Combined action of hormones may be more than just additive! 2 or more hormones work together to produce a particular effect Effects may be additive, as when E and NE each affect the heart in the same way. Effects may be complementary, as when each hormone contributes a different piece of an overall outcome.

Permissiveness One hormone makes target cell more responsive to a second hormone E.g.: Exposure to estrogen uterus more responsive to progesterone. Antagonism Insulin and glucagon both affect adipose tissue. 1)Insulin stimulates fat storage 2)Glucagon stimulates fat breakdown. Hormone Antagonists and Cancer: Tamoxifen as an exmaple of a SERM (see Clinical App, p. 325) Effects of hormone concentrations on tissue response Hormone half-life Time for plasma concentration of a given amount of hormone to

be reduced by half (mins to days) Liver removes most hormones from blood conversion to less active products Pharmacological hormone levels (?) binding to receptors of related hormones widespread side effects. E.g.: Steroid abuse Upregulation of receptors leads to priming effect Downregulation of receptors due to prolonged exposure to high concentrations of hormone. Desensitization can be avoided by releasing hormones in spurts = pulsatile secretion MECHANISMS OF HORMONE ACTION Hormones bind to _________on or in _____cells. Binding is highly specific

Hormone has high affinity Saturation occurs Location of hormone receptors? What is determining factor? Nuclear Hormone Receptors for Steroid and Thyroid hormones Two regions on the receptor: 1)Ligand-binding domain for the hormone 2)DNA-binding domain for DNA These hormones act as transcription factors

Fig11.4 Steroid hormone Steroid Hormone Receptors H Receptor protein for steroid hormone Ligand-binding domain DNA-binding

domain Half-sites DNA (a) Hormoneresponse element Target gene Dimerization of receptor Steroid hormone

H H Steroid hormone DNA Fig. 11.5 Genetic transcription (b) mRNA Compare to

Fig11.4 There is also nongenomic action involving 2nd messenger systems Which reaction is faster ? Coactivator and Corepressor... ....molecules often used in addition to the steroid hormone. They bind to nuclear receptor proteins at specific regions different effects of a given hormone in different cells Cytoplasm Nucleus

Thyroid Hormone Action DNA 4 Receptor protein T3 T4

Carrier protein (TBG) 1 T3 3 mRNA 6 Protein synthesis T3

Binding protein T3 2 T4 Fig. 11.6 Blood 5 mRNA

T4 Target cell 7 Thyroid hormone response Hormones That Use 2nd Messengers Catecholamines, polypeptides, proteins, and glycoproteins Cannot cross plasma membrane (?) bind to cell surface receptors Activate intracellular mediators called 2nd messenger via __________

Know adenylate (adenyl) cyclase / cAMP pathway only Adenylate Cyclase (cAMP) System E and NE Fig. 11.8 PITUITARY GLAND Other name? Hypothalamus Optic chiasma

Infundibulum Anterior lobe (__________________) Posterior lobe (________________) Fig. 11.12 Neurohormones of Posterior Pituitary 2 neurohormones (?) Both are peptides (9 aa) transported in secretory vesicles via axonal

transport Compare to Fig 11.13 Hormones of Anterior Pituitary 6 Hormones (names?) A Trophic hormone controls the secretion of another hormone. Target gland hypertrophies in response to trophic hormone. Hypothalamic trophic hormones and the hypothalamo-hypophyseal _________system Review Table 11.6 and compare to Fig. 11.14 Feedback Control of Anterior Pituitary

Final product regulates secretion of pituitary hormones: negative feedback inhibition Hypothalamus anterior pituitary target tissue axis Inhibition at pituitary level, inhibiting response to hypothalamic hormones. at hypothalamus level, inhibiting secretion of releasing hormones. Negative Feedback Loops in Complex Endocrine Pathways

Compare to Fig 11.16/17 Hypothalamus IC1 Ant. pituitary IC2 Endocrine gland IC3 Target tissue Hormones serve as negative feedback signals:

Short-loop vs. long-loop negative feedback. Feedback patterns are important in diagnosis of ES pathologies Higher Brain Controls Since hypothalamus receives input from higher brain regions, emotions can alter hormone secretion! Pituitary-gonad axis: At least 26 brain regions and olfactory neurons send axons to the GnRH-producing neurons. Pituitary-adrenal axis: Psychological stress influences CRH production Hot field:

neuropsychophysiology 11.4 Adrenal Glands Hormones? Clinical Application: Cushings syndrome Addisons disease Primary adrenal insufficiency Secondary adrenal insufficiency Clinical Application Exogenous glucocorticoids: Prednisone etc. What happens to

adrenal cortex ?? Not in book Endocrine Pathologies Unbalance leads to disease Due to: 1. Hypersecretion (excess) 2. Hyposecretion (deficiency) 3. Abnormal target tissue response 1. Hypersecretion Due to ? __________________ Iatrogenic ( gland atrophy)

Normal effects of hormone exagerated Symptoms accordingly Examples: Cushings Syndrome Gigantism Graves disease Gigantism According to GWR: The tallest man living is Sultan Ksen (Turkey, born: December 10, 1982) Measured in at 251 cm (8 ft 3

in) in Ankara, Turkey, on 08 February 2011. Hyperthyroidism Thyroid hormone? Most common cause: Graves' disease see CLINICAL APPLICATION Autoantibodies (TSI) bind to TSH receptor and stimulate thyroid hormone production Activation by TSI is not subject to normal negative feedback loop. Left exophthalmus in Graves disease 2. Hyposecretion: Normal effects of hormone diminished or absent

Symptoms accordingly Primary hyposecretion. Due to ? Secondary hyposecretion. Due to ? Examples: Addisons disease Dwarfism Hypothyroidism Hypothyroidism Most common cause in US: Hashimoto's thyroiditis = Chronic thyroiditis Chronic autoimmune disease

Hypothyroidism Other causes surgical removal of thyroid gland radioactive iodine treatment external radiation deficiency in dietary iodide consumption: Endemic or iodinedeficiency goiter Fig. 11.25 3. Abnormal Tissue Responsiveness

Hormone levels normal, target unresponsive Due to: Abnormal hormone / receptor interaction Abnormal signal transduction Diagnosis of Endocrine Pathologies Primary Pathology Defect arises in last integration center in the reflex Examples? Secondary Pathology Defect arises in one of the trophic integration centers Examples? Which of the following cortisol hypersecretion scenarios

points to an example of a 1 endocrine disorder? A. Decreased CRH, followed by increased ACTH, leading to increased cortisol. B. Increased TRH, leading to increased TSH, leading to increased thyroid hormone. C. Decreased CRH, leading to decreased ACTH, followed by increase in cortisol. D. Increased CRH, leading to increased ACTH, leading to increased cortisol. Which of the sets of lab values below would indicate Graves disease? Explain. Patient Serum T4

Serum TSH A 6 g/dl 1.5 U/ml B 14 g/dl .25 U/ml C

2.5 g/dl 20 U/ml D 16 g/dl 10 U/ml Normal 4.6-12 g/dl 0.5 - 6 U/ml

The End

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