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43 Cards in this Set
- Front
- Back
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Essential for coordinating the functions of interdependent systems
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Communication within and between cells and organ systems is a central component of multicellular organisms
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1. Nervous system
- Neurotransmitters 2. Immune system - Cytokines 3. Endocrine signaling mechanisms - Circulating hormones (distal action) 4. Autocrine/paracrine signaling mechanisms - Cytokines, growth factors, hormones (self/local action) |
Systems in higher eukaryotes rely heavily on communication by signaling with chemical messengers
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Essentially every cell in the body is responsive to multiple signaling mechanisms, which modulate their proliferation, lifespan and function
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Response to signaling is mediated by specific receptors for each chemical messenger, with few examples of cross-reactivity.
Do not respond to chemical signals unless it has the chemical receptor. |
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Chemical messengers are synthesized and...
Secreted into the intracellular space to modulate cell function without entering the bloodstream |
Autocrine and Paracrine System
Autocrine Target sites on same cell Paracrine Target sites on adjacent cell. Key: Do not enter the bloodstream. Concentrations are low. |
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Hormones are synthesized by specialized glands.
Secreted directly into the bloodstream for transport to target tissues to control their activity. |
The Endocrine System
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Hormones circulate in plasma in low concentrations (nM to mM), so have a high affinity for their receptors
Synthesis and secretion of hormones is highly regulated Many hormones are transported in blood by special carriers Only cell types that express specific receptors for a hormone are responsive Hormones are not secreted at a constant rate, but in response to some stimulus Hormones can elicit multiple responses Mechanisms exist for the inactivation/degradation of hormones, so their half-life in blood is limited |
Properties of hormones
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Insulin - in response to glucose concentration
Epinepherine - in response to stress Estrogen - in response to menstrual cycle or pregnancy |
Hormones are not secreted at a constant rate, but in response to some stimulus
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Insulin stimulates glucose uptake and protein synthesis
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Hormones can elicit multiple responses
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Insulin t1/2 is about 6-9 minutes
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Mechanisms exist for the inactivation/degradation of hormones, so their half-life in blood is limited
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1. Peptides or amino acid derivatives
2. Derivatives of cholesterol or a precursor (steroids) 3. Derivatives of polyunsaturated C-20 fatty acids (eicosanoids) |
Classification of Hormones
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What is the hormone type?
Insulin, glucagon, growth hormone, thyroid hormone, epinephrine Water soluble; most can travel in the blood stream without carriers Generally act by binding to receptors on the surface of cell membranes |
Peptides or amino acid derivatives
Insulin Glucagon Growth hormone Thyroid hormone Epinephrine |
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What is the hormone type?
Cortisol, aldosterone, testosterone, estradiol, vitamin D, vitamin A Water insoluble; need to associate with carrier molecules for transport in blood Can pass through cell membranes easily (lipid derived) Generally act by binding to receptors within the cell |
Derivatives of cholesterol or a precursor (steroids)
Cortisol Aldosterone Testosterone Estradiol Vitamin D Vitamin A |
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What is the hormone type?
Prostaglandins, thromboxanes, leukotrienes Generally act locally in autocrine or paracrine functions Usually have short half-lives |
Derivatives of polyunsaturated C-20 fatty acids (eicosanoids)
Prostaglandins Thromboxanes Leukotrienes |
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Name the metabolic regulatory hormone:
Major functions: a. Promotes fuel storage after food intake b. Promotes growth Major metabolic effects: a. Stimulates glucose storage as glycogen in muscle & liver b. Stimulates fatty acid synthesis and storage after high carbohydrate intake Stimulates amino acid uptake & protein synthesis |
Insulin
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Name the metabolic regulatory hormone:
Major functions: a. Mobilized stored fuels b. Maintains blood glucose during fasting Major metabolic effects: a. Activates gluconeogenesis & glycogenolysis during fasting b. Stimulates fatty acid release from adipose tissue |
Glucagon
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Name the metabolic regulatory hormone:
Major functions: a. Mobilizes stored fuels during acute stress Major metabolic effects: a. Stimulates glucose production from glycogen in muscle & liver b. Stimulates fatty acid release from adipose tissue |
Epinephrine
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Name the metabolic regulatory hormone:
Major functions: a. Provides for changing requirements over the long term Major metabolic effects: a. Stimulates amino acid mobilization from muscle protein b. Stimulates gluconeogenesis (liver) c. Stimulates fatty acid release from adipose tissue |
Cortisol
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A & B chains, C-peptide and Zn2+ are stored within a secretory vesicle until pancreatic B cells are stimulated to release the vesicle
Stimulation is caused by high [glucose] in blood Glucose transporter in B cells is GLUT2 - High Km for transport C-peptide has no activity, but has a longer lifetime in blood than insulin |
Insulin Synthesis and Release
A and B chains are linked via a dissulfide bond. [C-peptide] in blood is a measure of insulin release |
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1. The initial form of the insulin polypeptide is pre-proinsulin
a. The short N-term hydrophobic "pre" sequence is cleaved as it enters the RER 2. Proinsulin folds into the proper conformation, and disulfide bonds are formed 3. Proinsulin is transported in vesicles to the Golgi complex. 4. Proinsulin leaves the Golgi complex in vesicles, where a protease cleaves off the C-peptide and a few small amino acid sequences, resulting in active insulin. a. Insulin-containing vesicles are now available for exocytosis 5. The products of glycolysis in pancreatic b cells, resulting from the GLUT2- mediated transport of blood glucose into the beta cells, a. Stimulates the exocytosis of insulin from the vesicles. |
Steps in the synthesis & secretion of insulin
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1. Glucagon is a polypeptide hormone synthesized in the rough ER of pancreatic alpha cells as the 160 amino acid preproglucagon
2. Post-translational processing occurs as the prepeptide passes into the ER lumen to make proglucagon 3. Further processing in RER and Golgi converts to the mature peptide of 29 amino acids (~3500 Da) 4. Glucagon secretion does not vary as does insulin (i.e. default state). a. However its secretion is diminished in the presence of high [glucose] or high [insulin] 5. Catecholamines, cortisol, and certain GI hormones stimulate the secretion of glucagon |
Glucagon synthesis and release
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Hormone action is short-lived
- Most are rapidly inactivated and degraded - Permits maximal control of hormone responses |
Inactivation and degradation of hormones
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Most are endocytosed into the cell following interaction with receptors
Degraded to amino acids within the cell by proteases within lysosomes Some contain derivatized amino acids, particularly ring structures, that inactivate the hormone when lysed Some contain disulfide bonds that inactivate the hormone when reduced |
Inactivation of peptide hormones.
Such as: - Insulin - Glucagon - Growth hormone - Thyroid hormone - Epinephrine |
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Usually inactivated by chemical modification of the ring system
e.g. by reduction, hydroxylation |
Inactivation of steroid hormones.
Such as: - Cortisol - Aldosterone - Testosterone - Estradiol - Vitamin A - Vitamin D |
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Based on the ring structure of cholesterol (except retinoic acid), but with fewer carbons
Three major classes: 1. Mineralocorticoids (C-21) 2. Glucocorticoids (C-21) 3. Sex hormones - estrogens (C-18) - androgens (C-19) - progestins (C-21) Structures are very similar, especially within classes Specificity depends on recognition of specific structural moieties by receptors Only appropriate target organs will have specific receptors Synthesis of the hormone is dependent on stimulation by a "trigger" hormone, usually a peptide-derived substance |
Steroid hormone characteristics
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- Adrenal hormones that are regulated by stress
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Glucocorticoids (C21)
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Mineralocorticoids have _____ carbons
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21
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Glucocorticoids have ____ carbons
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21
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Estrogen has ___ carbons
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18
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Androgens have ____ carbons
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19
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Progestins have ___ carbons
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21
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Progesterone (C-21)
Secreted from the corpeus luteum; responsible for changes associated with the luteal phase of the menstrual cycle; Also a mammary gland differentiation factor An intermediate in the synthesis of other steroid horomes Trigger hormone is luteinizing hormone secreted by pituitary gonadotropes |
Progestins (C21)
Requisite intermediate of other steroid hormone synthesis First molecule synthesized by cholesterol in hormone production |
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Estradiol (C-18)
Produced in the ovary; the principle female sex hormone Responsible for secondary female sex characteristics Trigger hormone is follicle-stimulating hormone secreted by pituitary gonadotropes |
Estrogens (C18)
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Testosterone (C-19)
Synthesized in the testes; the principle male sex hormone Responsible for secondary male sex characteristics Trigger hormone is luteinizing hormone secreted by pituitary gonadotropes |
Androgens (C19)
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Aldosterone (C-21)
Produced in the zona glomerulosa of the adrenal cortex The principle mineralocorticoid Raises blood pressure and fluid volume; increases Na+ uptake Occurs in high levels during stress Trigger hormone is angiotensin secreted by the liver |
Mineralocorticoids (C21)
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Cortisol (C-21)
Produced in the zona fasciculata of the adrenal cortex The predominant glucocorticoid in humans Involves stress adaptation; elevates blood pressure and Na+ uptake Can cause slight elevation of liver glycogen Trigger hormone is ACTH secreted by pituitary corticotropes |
Glucocorticoids (C21)
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Steroid hormones are not very water soluble
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Require a carrier protein for transport in blood.
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Name the steroid hormone carrier protein for:
Cortisol |
Cortisol-binding globulin (CBG)
aka transcortin |
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Name the steroid hormone carrier protein for:
Testosterone (high affinity) Estradiol (lower affinity) |
Sex hormone-binding globulin (SHBG)
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Name the steroid hormone carrier protein for:
Androgen |
Androgen-binding protein (ABP)
Primarily functions locally in testes |
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Name the steroid hormone carrier protein for:
Generalized carrier Especially important for aldosterone |
Albumin
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Steroid hormone synthesis occurs in the _________ matrix
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mitochondrial
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This enzyme uses cytochrome p450
Converts cholesterol (C27) to Pregnenolone (C21) |
Cholesterol desmolase
also known as: Side chain cleavage enzyme (P450scc) |
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Synthesis of:
- Pregnenolone (C21) - Testosterone (C19) - Estradiol (C18) - Aldosterone (C21) - Progesterone (C21) - Cortisol (C21) Occurs in what organnelle? |
Mitochondrial matrix
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