Endocrine System Chapter 7 15
Endocrine Endocrine System: System Cont. collection of structures (glands,cells) which secrete hormones directly into the Chapter 7 circulation to affect metabolism, reproduction, growth, etc. 2
Hormones can travel long distances via circulatory system Endocrine Cell Target Cell Hormones: Released into the blood by endocrine Response glands/cells to affect distant targets 3
Different Hormone Classes Definition of Hormones Hormones Lots of ways are: to define a hormone: secreted Where is by it made? a cell or group of cells secreted What target into cell(s) the blood does it act on? can Does be it transported bind to a GPCR, to a distant tyrosine target kinase, or intracellular receptor? exert their effects at very low concentrations What is the molecule made out of? 6
All hormones are derived from one of three molecules Hormone Derived from Protein Amino Acid Cholesterol 7
When released, peptide hormones act by binding to cell-surface receptors Peptide hormone Peptide hormone receptor Extracellular Intracellular 8
When released, peptide hormones act extracellularly Peptide hormones are lipophobic (don t like lipids in cell membrane), water soluble, and dissolve in plasma Must bind to receptors on the cell surface (because they CANNOT cross cell membrane) Many work through camp second messenger systems Some through tyrosine kinase receptors 10
All hormones are derived from one of three molecules Hormone Derived from Protein Amino Acid Cholesterol 11
Cellular membranes are made up of lipids (and cholesterol) Cholesterol derived hormones can cross membrane 12
When released, steroid hormones act intracellularly Peptide hormone Steroid hormone Extracellular Intracellular 13
Figure 7.5b ESSENTIALS Steroid Hormones Steroid hormones bind to their receptors inside the cell Blood vessel Steroid hormone Cell surface receptor Most hydrophobic steroids are bound to plasma protein carriers. Only unbound hormones can diffuse into the target cell. Rapid responses Protein carrier Nucleus Steroid hormone receptors are in the cytoplasm or nucleus. Cytoplasmic receptor Nuclear receptor DNA Some steroid hormones also bind to membrane receptors that use second messenger systems to create rapid cellular responses. Interstitial fluid The receptor-hormone complex binds to DNA and activates or represses one or more genes. Cell membrane Endoplasmic reticulum Transcription produces mrna Activated genes create new mrna that moves back to the cytoplasm. New proteins Translation Translation produces new proteins for cell processes. Typically work to activate transcription of new proteins 15 2013 Pearson Education, Inc.
Figure 7.3 ESSENTIALS Peptide Hormone Synthesis and Processing Slide 6 Peptide Processed mrna Preprohormone Ribosome Endoplasmic reticulum (ER) Messenger RNA on the ribosomes binds amino acids into a peptide chain called a preprohormone. The chain is directed into the ER lumen by a signal sequence of amino acids. Signal sequence Prohormone Transport vesicle Enzymes in the ER chop off the signal sequence, creating an inactive prohormone. Packaged Processed Steroid hormones cannot be packaged into secretory vesicles. They Golgi complex can t be stored. Why? Cytoplasm Secretory vesicle Active hormone Peptide fragment The prohormone passes from the ER through the Golgi complex. Secretory vesicles containing enzymes and prohormone bud off the Golgi. The enzymes chop the prohormone into one or more active peptides plus additional peptide fragments. Stored ECF Release signal The secretory vesicle releases its contents by exocytosis into the extracellular space. Plasma Capillary endothelium To target The hormone moves into the circulation for transport to its target. 14 2013 Pearson Education, Inc.
All hormones are derived from one of three molecules Hormone Derived from Protein Amino Acid Cholesterol 17
Figure 7.6 Most amine hormones are derived from the amino acid tyrosine. Tyrosine is the parent amino acid for catecholamines and thyroid hormones. Catecholamines are made by modifying the side groups of tyrosine. Thyroid hormones are synthesized from two tyrosines and iodine (I) atoms. Dopamine Thyroxine (Tetraiodothyronine, T 4 ) Norepinephrine Epinephrine Neurohormones w/ extracell. receptors Triiodothyronine (T 3 ) 19 Intracell. receptors just like steroids do
Another defining characteristic of different hormones: half-life 20
Hormones can also be classified based on half-life Starting amounts of green dots. Time = 0 After 1 half-life. Time = 10 min. After 2 half-lives. Time = 20 min. Half-life = amount of time for half of the remaining molecule to decay. More stable molecules have a longer half-life 21
Hormones can also be classified based on half-life Starting amounts of green dots. Time = 0 After 1 half-life. Time = 10 min. After 2 half-lives. Time = 20 min. Half-life = amount of time for half of the remaining molecule to decay. More stable molecules have a longer half-life 22
Hormones can also be classified based on half-life Starting amounts of green dots. Time = 0 After 1 half-life. Time = 10 min. After 2 half-lives. Time = 20 min. Half-life = amount of time for half of the remaining molecule to decay. More stable molecules have a longer half-life 23
Figure 7.5b ESSENTIALS Steroid Hormones Protein carriers help protect hormones from degradation in the blood Blood vessel Steroid hormone Cell surface receptor Most hydrophobic steroids are bound to plasma protein carriers. Only unbound hormones can diffuse into the target cell. Rapid responses Protein carrier Nucleus Steroid hormone receptors are in the cytoplasm or nucleus. Cytoplasmic receptor Nuclear receptor DNA Some steroid hormones also bind to membrane receptors that use second messenger systems to create rapid cellular responses. Interstitial fluid The receptor-hormone complex binds to DNA and activates or represses one or more genes. Cell membrane Endoplasmic reticulum Transcription produces mrna Activated genes create new mrna that moves back to the cytoplasm. New proteins Translation Translation produces new proteins for cell processes. Steroid hormones have a longer half-life. 2013 Pearson Education, Inc. 24
All hormone properties can be predicted by one fact: is the hormone hydrophobic or hydrophilic? 25
I bet you can predict all the properties of a given hormone if 26 you only know whether it is lipophilic or lipophobic
Steroid Hormones Steroid hormones are lipophilic (they like the lipids in the cell membrane) Are not very soluble in plasma (because they are hydrophobic), so travel bound to protein carrier. Typically bind intracellular receptors (because they CAN cross membrane due to being lipophilic) Typically have genomic effects (affect DNA transcription) 16
Goals for today: Hormone properties-what distinguishes them from one another? Hydrophobic/hydrophilic property determines all others. Hypothalamus-pituitary pathway Pituitary is a dual structure, part endocrine part neural. But both release hormones, some tropic. Endocrine pathologies-thyroid and adrenal cortex hormones 16
Text Patient: Edna So this is how we secrete hormones from the Age: 67 pituitary. How do we regulate this secretion? Swollen, Body Does a Great Job of Shutting enlarged Off Signals When They re Not Needed thyroid gland Anymore Via Negative Feedback (goiter) Let s look at a couple of examples of this Let s remind negative feedback: thyroid hormone and ourselves of cortisol production the pathway... 17
Thyroid Hormone: -Increases basal metabolic rate -Increased production of heat -Breakdown of proteins/fats -Increased O2 consumption -Increased ATP consumption -Increased activity/expression of Na+/K+ pump activity. 18
Figure 7.6 Most amine hormones are derived from the amino acid tyrosine. Tyrosine is the parent amino acid for catecholamines and thyroid hormones. Catecholamines are made by modifying the side groups of tyrosine. Thyroid hormones are synthesized from two tyrosines and iodine (I) atoms. Dopamine Thyroxine (Tetraiodothyronine, T 4 ) Norepinephrine Epinephrine Triiodothyronine (T 3 ) 19
Patient: Edna Age: 67 Text So this is how we secrete hormones from the pituitary. How do we regulate this secretion? Iodine deficiency = No T3 Body Does a Great Job of Shutting Off Signals When They re Not Needed No T3 = No neg. Anymore Via Negative Feedback feedback No neg. feedback = Increased TSH Let s look at a couple of examples of this negative feedback: thyroid hormone and Increased TSH cortisol production Goiter overstimulates thyroid growth 20
Kyle, Age 7 Kyle, Age 5 21
Cortisol is the stress hormone 22
Control Pathway for Cortisol Secretion Cortisol is a steroid hormone secreted by the adrenal cortex. ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone. Hypothalamus CRH Anterior pituitary Short-loop negative feedback Short-loop feedback: Tropic hormones produced negatively regulate themselves. ACTH Adrenal cortex To target tissue FIGURE QUESTION Draw in the short-loop negative feedback Cortisol Target tissue Response Long-loop negative feedback Long-loop feedback: Final hormone produced negatively regulates 23 hormone secretion upstream
Cortisol stimulates fat breakdown, glycogen breakdown, protein breakdown... 24
So does Kyle likely have too much or too little cortisol? 25
Cushing s syndrome: HYPERcortisolism Fat stretch marks 26 Fat
How can we diagnose lack of negative feedback? Where in the pathway is the problem? 27
Figure 7.14 Primary and secondary hypersecretion of cortisol Primary Hypersecretion Due to Problem with Adrenal Cortex Secondary Hypersecretion Due to Pituitary Problem Secondary Hypersecretion Due to Hypothalamic Problem Hypothalamus CRH HYPERSECRETING Hypothalamus CRH TUMOR IN CRH HYPOTHALAMUS Anterior pituitary ACTH TUMOR IN ANT. PITUITARY, EXCESS ACTH ACTH Anterior pituitary ACTH TUMOR IN ADR. CORTEX, EXCESS CORTISOL Cortisol Adrenal cortex Cortisol Adrenal cortex Cortisol Negative feedback fails Symptoms of excess Symptoms of excess Symptoms of excess CRH levels low ACTH levels low Cortisol levels high CRH levels low ACTH levels high Cortisol levels high CRH levels high ACTH levels high Cortisol levels high 28
Figure 7.14 Primary and secondary hypersecretion of cortisol Primary Hypersecretion Due to Problem with Adrenal Cortex Secondary Hypersecretion Due to Pituitary Problem Secondary Hypersecretion Due to Hypothalamic Problem Hypothalamus CRH HYPERSECRETING Hypothalamus CRH TUMOR IN CRH HYPOTHALAMUS Anterior pituitary ACTH TUMOR IN ANT. PITUITARY, EXCESS ACTH ACTH Anterior pituitary ACTH TUMOR IN ADR. CORTEX, EXCESS CORTISOL Cortisol Adrenal cortex Cortisol Adrenal cortex Cortisol Negative feedback fails Symptoms of excess Symptoms of excess Symptoms of excess CRH levels low ACTH levels low Cortisol levels high CRH levels low ACTH levels high Cortisol levels high CRH levels high ACTH levels high Cortisol levels high 29
Figure 7.14 Primary and secondary hypersecretion of cortisol Primary Hypersecretion Due to Problem with Adrenal Cortex Secondary Hypersecretion Due to Pituitary Problem Secondary Hypersecretion Due to Hypothalamic Problem Hypothalamus CRH HYPERSECRETING Hypothalamus CRH TUMOR IN CRH HYPOTHALAMUS Anterior pituitary ACTH TUMOR IN ANT. PITUITARY, EXCESS ACTH ACTH Anterior pituitary ACTH TUMOR IN ADR. CORTEX, EXCESS CORTISOL Cortisol Adrenal cortex Cortisol Adrenal cortex Cortisol Negative feedback fails Symptoms of excess Symptoms of excess Symptoms of excess CRH levels low ACTH levels low Cortisol levels high CRH levels low ACTH levels high Cortisol levels high CRH levels high ACTH levels high Cortisol levels high 30