-
What are the cell types in the Islet of Langerhans, and what hormones are released by each cell type?
- Alpha cells: located at the periphery of the islet; secrete glucagon
- Beta cells: located throughout the islet; secrete insulin
- Delta cells: few in number, located throughout islet; secrete somatostatin
-
What is the functional significance of the vascularization of the Islets of Langerhans?
- Rich vascularization for circulation of hormones secreted by the islet cells
- Blood flows from the center to the periphery, so alpha and delta cells are exposed to high concentrations insulin from beta cells. This insulin inhibits glucagon release
-
What is the effect of the Parasympathetic Nervous System on glucagon and insulin secretion from alpha and beta cells?
Stimulates the secretion of insulin, glucagon, somatostatin, and pancreatic polypeptide
-
What is the effect of the Sympathetic Nervous System on glucagon and insulin secretion from alpha and beta cells?
Inhibits basal and glucose-stimulated insulin secretion and somatostatin release and stimulates glucagon and pancreatic polypeptide secretion
-
Describe the synthesis of insulin via processing of proinsulin. Describe the mature form of insulin. Describe source of C-peptide and its use to assess the secretory function of the beta cells.
- In the ER, the C-peptide is cleaved from proinsulin to generate the mature form of insulin.
- Insulin is composed of an alpha chain and a beta chain held together by two disulfide bonds.
- The liver does not readily degrade c-peptide (like insulin), so C-peptide levels can be used to assess the production of insulin.
-
Describe the regulation of insulin secretion and electrophysiological mechanism of insulin secretion
- **Glucose is the principal stimulus for insulin release
- 1. Glucose leads to an increased ATP/ADP ratio from glycolysis and the Krebs cycle.
- 2. This results in the inhibition and closure of ATP-sensitive K+ channels.
- 3. K+ channel closure results in depolarization of the PM and opening of voltage-dependent Ca2+ channels.
- 4. Increased [Ca2+] causes release of insulin
-
What 4 hormones increase or stimulate insulin secretion?
-
What 3 hormones inhibit insulin secretion?
- Epinephrine
- Norepinephrine
- Somatostatin
-
What is the biphasic release of insulin?
There is an initial rapid release of preformed insulin followed by a more sustained release of newly synthesized insulin
-
What does insulin stimulate within Carbohydrate Metabolism?
- Glucose transport in adipose tissue and muscle
- Rate of glycolysis in muscle and adipose tissue
- Glycogen synthesis in adipose tissue, muscle, and liver
-
What does Insulin inhibit in Carbohydrate Metabolism?
- Glycogen breakdown in muscle and liver
- Rate of glycogenolysis gluconeogenesis in the liver
-
What does Insulin stimulate in Lipid Metabolism?
- Fatty acid and triacylglycerol synthesis in tissues
- Uptake of triglycerides from the blood into adipose tissue and muscle
- Rate of cholesterol synthesis in the liver
-
What does Insulin inhibit in Lipid Metabolism?
- Lipolysis in adipose tissue, lowering the fatty acid level
- Fatty acid oxidation in muscle and liver
- Ketogenesis
-
What does Insulin stimulate in Protein Metabolism?
- Amino acid transport into tissues
- Protein synthesis in muscle, adipose tissue, liver, and other tissues
-
What does Insulin inhibit in Protein Metabolism?
- Protein degradation in muscle
- Urea formation
-
What factors stimulate glucagon secretion?
- High Amino Acid Levels
- Epinephrine
- Vagal Stimulation
-
What factors inhibit glucagon secretion?
- Hyperglycemia
- Somatostatin
-
What effeect does Glucagon have on Glucose-6-phosphatase, and what metabolic response does this induce?
- Increased expression of Glucose-6-Phosphatase
- Frees glucose to enter the circulation
-
What effect does Glucagon have on Glucokinase, and what metabolic response does this induce?
- Suppresses Glucokinase
- Deceases glucose entry into the glycolytic cascade
-
What effect does Glucagon have on Glycogen Phosphorylase, and what metabolic response does this induce?
- Phosphorylates (activates) Glycogen Phosphatase
- Stimulates glycogenolysis
-
What effect does Glucagon have on Glycogen Synthase, and what metabolic response does this induce?
- Inhibits Glycogen Synthase
- Inhibits glycogen synthesis
-
What effect does Glucagon have on Phosphoenolpyruvate Carboxykinase, and what metabolic response does this induce?
- Stimulates its expression
- Stimulates gluconeogenesis
-
What effect does Glucagon have on Phosphofructokinase-2 (PFK-2), and what metabolic response does this induce?
- Inactivates it
- Inhibits Glycolysis
-
What effect does Glucagon have on Fructose-6-Phosphatase, and what metabolic response does this induce?
- Activates it
- Stimulates Gluconeogenesis
-
What effect does Glucagon have on Pyruvate Kinase, and what metabolic effect does this induce?
- Suppresses its activity
- Decreases Glycolysis
-
Lung cancers commonly secrete what 3 hormones?
- Parathyroid Hormone
- Antidiuretic Hormone
- ACTH
-
What percentage of cholesterol for hormone synthesis comes from de novo synthesis, and what percentage comes from cholesterol in blood bound to LDL?
-
Which form of the hormone is the active form?
The free form -- the hormone must dissociate from the binding protein to be active
-
What is it called when the effect of one hormone requires the presence of a second hormone (the effects of the second hormone allow the actions of the first hormone)?
What is an example of this?
- Permissive Action
- Thyroid hormone has permissive effects in that it is needed for epinephrine to have its effects
-
This is a hormone that stimulates the release of another hormone.
Trophic Hormone
-
What is the major integrative center for homeostatic control systems?
Hypothalamus
-
Are the circulating hormone levels in the endocrine system high or low?
Very low
-
What are the three general chemical classifications of hormones?
-
What are the four amine-based hormones?
- Dopamine (catecholamine)
- Norepinephrine (catecholamine)
- Epinephrine (catecholamine)
- Thyroid Hormone (T3 &T4)
-
Which form of Thyroid Hormone is the active form?
T3
-
What is the precursor to all amine-based hormones?
Tyrosine
-
What is the precursor to all steroid hormones?
Cholesterol
-
What is the specificity of the Endocrine System due to?
Expression of hormone receptors on target tissues
-
What are the 6 Steroid Hormones?
- Aldosterone (mineralocorticoid)
- Cortisol (glucocorticoid)
- Testosterone (androgen)
- Estradiol or Estrogen (androgen)
- Progesterone (androgen)
- Vitamin D
-
What is the major steroid secreting gland?
Adrenal Cortex
-
Within the adrenal cortex, what hormone is secreted from the Zona Glomerulosa?
Aldosterone
-
Within the adrenal cortex, where is Aldosterone secreted from?
Zona Glomerulosa
-
Within the adrenal cortex, what hormones are secreted from the Zona Fasiculata?
-
Within the adrenal cortex, where are Cortisol and the Androgens secreted from?
- Zona Fasiculata
- Zona Reticularis
-
Within the adrenal cortex, what hormones are secreted from the Zona Reticularis?
-
What hormones are secreted from the adrenal medulla?
- Epinephrine
- Norepinephrine
-
Where are Epinephrine and Norepinephrine secreted from?
Adrenal Medulla
-
Other than the adrenal cortex and medulla, what are the steroid secreting glands?
- Gonads (Testes & Ovaries)
- Placenta
-
How does the synthesis of Peptides take place?
- Preprohormone: signal sequence is clipped in the ER
- Prohormone: packaged in Golgi where further cleaved to the
- Hormone: stored in vesicle, ready for release
-
Proopiomelanocortin (POMC) is a pre-cursor for what important molecule?
ACTH
-
Proopiomelanocortin (POMC) is a preprohormone that can make multiple different hormones. How are different hormones cleaved?
It is dependent on the enyzme doing the cleaving. Different tissues possess different enzymes, which is why different hormones are expressed there
-
How do Catecholamines and most peptides travel through blood?
The are water soluble so can travel in free form in blood
-
How do Steroids, Thyroid Hormone, Growth Hormone, and Insulin-like Growth Factor (IGF-1) travel through blood?
They are hydrophobic, so must be carried by being bound to proteins in blood. An equilibrium exists between bound and free forms of these hormones
-
What are the two functions of the bound hormone?
- Reservoir of hormone in blood: reduces the fluctuation of hormone levels -- helps buffer hormone release to maintain a stable level
- Increases half-life of hormone: decreases metabolism, which increases half-life
-
In general, proteins that have chronic long-term effects are in what state? Hormones with acute short-term effects circulate in what state?
-
Can protein-bound hormones be metabolized?
No, only those in the free form can
-
What are the three functions of Metabolism for hormones?
- Inactivation: the metabolites are not biologically active
- Activation: some hormones must be metabolized to be converted to their active form (i.e. T4 must be cleaved to T3)
-
What are the three major sites of metabolism?
- Liver
- Kidney
- Plasma -- catacholamines and peptides
-
What is the major membrane-bound receptor for hormones?
G-protein coupled receptor
-
What is the major insulin receptor?
Tyrosine Kinase
-
What is the major Growth Hormone receptor?
JAK-STAT Pathway
-
In addition to fast effects, membrane bound receptors can also do what, which gives them long-term effects as well?
Affect gene expression
-
Steroids, Thyroid Hormone, and Vitamin D all bind to receptors in the cytoplasm and are then transported where? What can the hormone-receptor complex then do?
- Taken to Nucleus
- Binds to DNA and alters gene expression and protein synthesis
-
Why is thyroid hormone required for epinephrine to have its metabolic effects (through permissiveness)?
Because thyroid hormone is required for expression of beta receptors
-
How does up regulation work?
When don't have enough stimulus, get an up regulation of the system where we increase the number of receptors or level of responsiveness to compensate
-
How does down regulation work?
When there is too much stimulus, decrease the number of receptors or level of responsiveness to compensate (type II diabetes)
-
What are the three patterns of hormone secretion?
- Pulsatile: hormones are released in pulses (so don't get a down regulation)
- Daily Cycles/Circadian Patterns: every 20-28 hours with GH and Cortisol
- Monthly Cycles: menstruation
-
What are the control inputs in hormone release?
- Plasma Concentrations of mineral ions or nutrients: ie insulin secretion regulated by plasma glucose levels
- Neuronal Control: hormone is released from hypothalamus into hypothalamo-pituitary system, which takes it to the anterior pituitary gland, then into circulation to target tissues.
- Hormonal Control: GH, TH, and cortisol
-
What are the two feedback systems for growth hormone?
- Hypo releases GHRH (positive feedback molecule) and SS (negative feedback molecule).
- Growth hormone is stimulated to be released (or not) from anterior pituitary, where it can move to target tissues
-
What is the hormonal control mechanism for thyroid hormone?
Hypo releases TRH, which is a positive feedback regulator of the release of TSH by the anterior pituitary gland, where TSH stimulates the release of thryoid hormone from the Thryoid.
-
What is the hormonal control mechanism for cortisol?
Hypo releases CRH, a positive feedback regulator of the release of ACTH by the anterior pituitary. ACTH then stimulates the release of cortisol from the adrenal cortex
-
What is the major integrative center for homeostatic control systems?
Hypothalamus
-
________ _________ are released from the hypothalamus and regulate the release of hormones from the anterior pituitary gland.
Hypophysiotropic (Trophic) Hormones
-
This is the base of the hypothalamus?
Median Eminence
-
This connects the hypothalamus with the pituitary, and contains the hypothalamo-pituitary portal system. The hypophysiotropic hormones travel from the hypothalamus to the anterior pituitary via the hypothalamo-pituitary portal system.
Infundibulum
-
How do the hypophysiotropic hormnes travel from the hypothalamus to the anterior pituitary gland?
Through the hypothalamo-pituitary portal system in the infundibulum
-
This is located in the sella trucica of the sphenoid bone, and is divided into two lobes.
Pituitary
-
This is an outgrowth of the hypothalamus, and is therefore neuronal tissue. Neurons from hypothalamus project here, and activation of those neurons causes release of hormones into the systemic circulation.
Posterior Pituitary
-
This is composed of tissue originating from Rathke's pouch in the pharynx. Hormones released from here enter the systemic circulation and travel to their target tissue. The target tissue can be another gland or a tissue that produces the final physiological response to the hormone.
Anterior Pituitary
-
Hypophysiotrophic hormones released from the hypothalamus travel to the anterior pituitary via the hypothalamo-pituitary portal vessels. Hypophysiotropic hormones bind to receptors on specific troph cells in the anterior pituitary and do what?
Either stimulate or inhibit release of hormones from the troph cells.
-
What is the main source of hormonal feedback control?
Negative Feedback Loops: hormones inhibit the release of releasing and trophic hormones to help dampen hormone response. This keeps the hormone levels within a certain range
-
This is a type of hyposecretion that is due to some abnormality in the gland. There can be destruction of the gland, such as the destruction of beta cells in Type I Diabetes, or defects in hormone synthesis or metabolism, such as an iodine deficiency, which can lead to thyroid disease.
Primary Hyposecretion
-
Hashimoto's disease is an example of what?
Primary Hyposecretion
-
This is a type of hyposecretion in which the gland is normal but there is too little stimulus from the pituitary or trophic hormone. An example of this is Kallman's Syndrome, in which there is no LH or FSH released due to a lack of GnRH hormones in the hypothalamus. Therefore, there is a lack of sex hormones even though the gonads are normal.
Secondary Hyposecretion
-
Kallman's Syndrome is an example of?
Secondary Hyposecretion
-
In this type of hypersecretion, an abnormality in the gland is commonly caused by the presence of a hormone-secreting tumor, such as a thyroid adenoma, which causes excess thryoid release.
Primary Hypersecretion
-
A thyroid adenoma is an example of?
Primary Hypersecretion
-
In this type of hypersecretion, the gland is normal but there is too much stimulus from the pituitary or trophic hormone. An example is Cushing's Disease, in which there is a defect or hormone-secreting tumor in the pituitary that causes excess release of ACTH, which stimulates hypersecretion of cortisol.
Secondary Hypersecretion
-
Cushing's Disease is an example of?
Secondary Hypersecretion
-
In this type of hormone responsiveness, hormone secretion is normal, but the target cell does not respond to the hormone. This can be caused by a deficiency or lack of hormone receptors (ie. androgen insensitivity syndrome), an abnormality in receptor-signal transduction coupling (type II diabetes), or an abnormality in metabolic activation (conversion of testosterone to dihydrotestosterone).
Hyporesponsiveness
-
What are three abnormalities leading to Hyporesponsiveness?
- Deficiency or lack of hormone receptors: Androgen Insensitivity Sydrome
- Receptor-signal transduction coupling is abnormal: Type II Diabetes
- Metabolic activation is abnormal: Conversion of testosterone to dihydrotestosterone
-
This type of response results in an up regulation of hormone receptors, for example there is one to epinephrine with hyperthyroidism due to an up regulation of beta-adrenergic receptors.
Hyperresponsiveness
-
What are the two types of Endocrine Function Tests?
- Hormone Concentrations
- Dynamic Hormone Secretion Measurements
-
This Endocrine Function Test is measured in biological fluids (commonly plasma or urine). Radioimmune assays, immunometric assays or variations are most often used for measurements. Variations are due to pulsitile release, biological rhythyms and nutrition status. It is a static determination.
Within this test, hormones should be measured along with their regulatory factors (i.e. insulin and glucose)
Within this test, the target hormone should be measured with appropriate trophic hormones to determine is an ectopic site, such as a tumor, is causing elevations in hormone.
Hormone Concentrations
-
What are the two sub-types of Dynamic Hormone Secretion Measurements?
- Stimulation Tests
- Suppression Tests
-
In this type of Dynamic Hormone Secretion Test, trophic hormone or another stimulant is given to determine the ability of the gland or tissue to secrete hormone. An example is a glucose tolerance test.
Stimulation Tests
-
In this type of Dynamic Hormone Secretion Test, drugs or hormones are administered to determine if the feedback systems are functional. For example, a synthetic analogue of cortisol is used to see if the subsequent release of cortisol is suppressed.
Suppression Tests
|
|
