Endocrine SystemEndocrine System

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BackgroundBackground

There are two types of glands: There are two types of glands: Endocrine & ExocrineEndocrine & Exocrine

1. Endocrine: Ductless, secrete hormones into 1. Endocrine: Ductless, secrete hormones into surrounding tissue fluid, vascular or surrounding tissue fluid, vascular or lymphatic drainage receive hormones, lymphatic drainage receive hormones, examples of endocrine glands (pituitary, examples of endocrine glands (pituitary, thyroid, parathyroid, adrenal, pineal & thyroid, parathyroid, adrenal, pineal & thymus) & some organs also have discrete thymus) & some organs also have discrete areas of endocrine tissue as well as exocrine areas of endocrine tissue as well as exocrine tissue (pancreas, gonads & hypothalamus)tissue (pancreas, gonads & hypothalamus)

2. Exocrine: Have ducts & nonhormonal 2. Exocrine: Have ducts & nonhormonal products are directed to membrane products are directed to membrane surfacessurfaces

HormonesHormones

chemical substances secreted by cells into chemical substances secreted by cells into extracellular fluids, that regulate metabolic extracellular fluids, that regulate metabolic function of other cells in the bodyfunction of other cells in the body

ChemistryChemistry

ClassificationClassificationa. Amino acid-based a. Amino acid-based hormones (most hormones)hormones (most hormones)b. Steroid hormones (gonadalb. Steroid hormones (gonadaland adrenocortical hormones)and adrenocortical hormones)

Mechanism of action—increase or decrease Mechanism of action—increase or decrease rates of normal cellular activityrates of normal cellular activity1. Hormonal effects1. Hormonal effects

a. Alter plasma membrane permeabilitya. Alter plasma membrane permeabilityb. Alter protein or regulatory molecule b. Alter protein or regulatory molecule synthesissynthesisc. Activate or inactivate enzymec. Activate or inactivate enzymed. Induction of secretory activityd. Induction of secretory activitye. Stimulate mitosise. Stimulate mitosis

2. Mechanisms that transduce hormonal 2. Mechanisms that transduce hormonal signal into an intracellular changesignal into an intracellular changea. G-protein linked receptor activation of a. G-protein linked receptor activation of intracellular second messengers (amino acid-intracellular second messengers (amino acid-based hormones)based hormones)b. Direct gene activation (steroid hormones)b. Direct gene activation (steroid hormones)

3. Overview of second-messenger systems3. Overview of second-messenger systems a. Hormone binds plasma membrane receptora. Hormone binds plasma membrane receptorb. G-protein signals effector to produce an b. G-protein signals effector to produce an intracellular message (second messenger)intracellular message (second messenger)c. Second messenger mediates cellular c. Second messenger mediates cellular response to hormone (signaling cascades & response to hormone (signaling cascades & protein kinases)protein kinases)

4. Examples of signaling mechanisms4. Examples of signaling mechanismsa. cAMP a. cAMP b. PIP-Calcium signal mechanismb. PIP-Calcium signal mechanism

5. Direct gene activation 5. Direct gene activation a. Steroid hormones are lipid soluble (pass a. Steroid hormones are lipid soluble (pass through plasma membrane)through plasma membrane)b. Once inside, hormone binds to intracellular b. Once inside, hormone binds to intracellular receptor (activated complex is formed)receptor (activated complex is formed)c. Activated complex passes into nucleus and c. Activated complex passes into nucleus and binds to specific DNA sequencesbinds to specific DNA sequencesd. Association with DNA sequence turns on d. Association with DNA sequence turns on gene (gene sequence is transcribed)gene (gene sequence is transcribed)

Target cell specificityTarget cell specificity

1. Mediated by specific protein receptors1. Mediated by specific protein receptorsa. Receptors are localized to cells that are a. Receptors are localized to cells that are influenced by a given hormoneinfluenced by a given hormoneb. Hormones act as molecular triggersb. Hormones act as molecular triggers

2. Factors affecting target cell activation2. Factors affecting target cell activationa. Hormonal levelsa. Hormonal levelsb. Number of receptors on target cellb. Number of receptors on target cellc. Receptor affinity (can be up or down c. Receptor affinity (can be up or down regulated based on microenvironmental regulated based on microenvironmental conditions)conditions)

Hormonal activity—half-life, Hormonal activity—half-life, onset and durationonset and duration1. Half-life—measure of hormonal persistence 1. Half-life—measure of hormonal persistence in blood stream depends on rate of synthesis in blood stream depends on rate of synthesis and release, speed of removal or degradationand release, speed of removal or degradation2. Onset of effect is dependent on hormone 2. Onset of effect is dependent on hormone type (steroid: hours to days)type (steroid: hours to days)3. Duration is generally short (3. Duration is generally short (e.ge.g 20 minutes) 20 minutes) although depends on hormone typealthough depends on hormone type

Control of hormone releaseControl of hormone release

1. Typically negative feedback: Hormone 1. Typically negative feedback: Hormone secretion is triggered in response to a secretion is triggered in response to a stimulus & as hormone level increases, stimulus & as hormone level increases, target organ is affected & further target organ is affected & further hormone release is inhibited. hormone release is inhibited.

2. Types of stimuli: 2. Types of stimuli: HumoralHumoral (glands release (glands release hormones in direct response to changing hormones in direct response to changing levels of ions or nutrients, e.g., PTH release in levels of ions or nutrients, e.g., PTH release in response to changes in calcium levels), response to changes in calcium levels), neuralneural (nerve fibers stimulate hormonal (nerve fibers stimulate hormonal release, e.g., sympathetic activated release of release, e.g., sympathetic activated release of catecholamines from adrenal medulla) & catecholamines from adrenal medulla) & hormonalhormonal (release of hormones in response to (release of hormones in response to other hormones, e.g., hypothalamic releasing other hormones, e.g., hypothalamic releasing and inhibiting factors)and inhibiting factors)

Major Endocrine OrgansMajor Endocrine Organs

Pituitary (hypophysis)Pituitary (hypophysis)

1. General characteristics: 1. General characteristics: a.a. Connected to Connected to hypothalamus (part of brain) by infundibulum hypothalamus (part of brain) by infundibulum (stalklike connection between brain & endo-(stalklike connection between brain & endo-crine system), crine system), b.b. Two major lobes: Posterior & Two major lobes: Posterior & anterior, anterior, c.c. Posterior lobe + infundibulum = Posterior lobe + infundibulum = neurohypophysis, neurohypophysis, d.d. Anterior lobe (adeno- Anterior lobe (adeno-hyophysis) is comprised of glandular tissuehyophysis) is comprised of glandular tissuee.e. Highly vascular Highly vascular

2. Connections between posterior pituitary & 2. Connections between posterior pituitary & hypothalamus: hypothalamus: a.a. Posterior is an outgrowth of Posterior is an outgrowth of brain & maintains its neural connections, brain & maintains its neural connections, b.b. Neurons in supraoptic & paraventricular Neurons in supraoptic & paraventricular nuclei of hypothalamus give rise to hypothal-nuclei of hypothalamus give rise to hypothal-amic-hypophyseal tract (hormones synthesis amic-hypophyseal tract (hormones synthesis in secretory cells of hypothalamus: oxytocin in secretory cells of hypothalamus: oxytocin & antidiuretic hormone) & & antidiuretic hormone) & c.c. When neurons When neurons fire, hormones are released into capillary bed fire, hormones are released into capillary bed in posterior pituitaryin posterior pituitary

3. Connections between ant. pituitary & hypo-3. Connections between ant. pituitary & hypo-thalamus: thalamus: a.a. Anterior lobe is derived from Anterior lobe is derived from epithelial tissue, epithelial tissue, b.b. No direct connection No direct connection between post. pituitary or hypothalamus, between post. pituitary or hypothalamus, c.c. Vascular connection (hypophyseal portal Vascular connection (hypophyseal portal veins), veins), d.d. Releasing & inhibiting hormones Releasing & inhibiting hormones secreted by hypothalamus are carried by secreted by hypothalamus are carried by portal system to anterior pituitary (regulate portal system to anterior pituitary (regulate activity of secretory cells in ant. Pituitary)activity of secretory cells in ant. Pituitary)

Anterior pituitary hormonesAnterior pituitary hormones

1. Anterior pituitary is the Master gland1. Anterior pituitary is the Master gland2. Six hormones as well as a number of other 2. Six hormones as well as a number of other active moleculesactive molecules3. Tropic hormones (4/6): Regulate secretory 3. Tropic hormones (4/6): Regulate secretory activity of other endocrine glands:activity of other endocrine glands:• TSH: Thyroid-stimulating hormoneTSH: Thyroid-stimulating hormone• ACTH: Adrenocorticotropic hormoneACTH: Adrenocorticotropic hormone• FSH: Follicle-stimulating hormoneFSH: Follicle-stimulating hormone• LH: Lutenizing hormoneLH: Lutenizing hormone

4. Other hormones (2/6) have 4. Other hormones (2/6) have neuroendocrine targets:neuroendocrine targets:a. PRL: Prolactina. PRL: Prolactinb. GH: Growth hormoneb. GH: Growth hormone

5. Growth hormones5. Growth hormones

a. Produced by somatotropic cellsa. Produced by somatotropic cellsb. Stimulates most cells to grow & divideb. Stimulates most cells to grow & dividec. Major targets are bones and musclesc. Major targets are bones and musclesd. Anabolic hormone (promotes metabolism)d. Anabolic hormone (promotes metabolism)e. Growth-promoting effects are mediated e. Growth-promoting effects are mediated indirectly (IGFs: Insulin-like growth factors indirectly (IGFs: Insulin-like growth factors produced by liver and other tissues)produced by liver and other tissues)

f. Effects of growth hormone: f. Effects of growth hormone: SStimulates timulates uptake of amino acids from blood and their uptake of amino acids from blood and their incorporation into proteins, incorporation into proteins, sstimulates sulfur timulates sulfur uptake, uptake, mmobilizes fats from fat deposits, obilizes fats from fat deposits, ddecreases rate of glucose uptake and ecreases rate of glucose uptake and metabolism (diabetogenic effect: elevation of metabolism (diabetogenic effect: elevation of blood glucose)blood glucose)

g. Regulation by hypothalamic hormones g. Regulation by hypothalamic hormones (negative feedback): (negative feedback): • GHRH: growth hormone releasing hormone GHRH: growth hormone releasing hormone (somatocrinin) (somatocrinin) • GHIH: (growth hormone inhibiting hormone GHIH: (growth hormone inhibiting hormone (somatostatin)(somatostatin)

h. Abnormalities:h. Abnormalities:*Adolescent hypersecretion: Gigantism*Adolescent hypersecretion: Gigantism*Adult hypersecretion: Acromegaly (tissues *Adult hypersecretion: Acromegaly (tissues still sensitive to GH grow disproportionately) still sensitive to GH grow disproportionately) *Adult hyposecretion: Little effect (progeria: *Adult hyposecretion: Little effect (progeria: occurs when deficit is severe)occurs when deficit is severe)*Adolescent hyposecretion:Pituitary dwarfism*Adolescent hyposecretion:Pituitary dwarfism

6. Thyroid-stimulating hormone (TSH)6. Thyroid-stimulating hormone (TSH)a.a. Stimulates normal growth & activityStimulates normal growth & activityof thyroid glandof thyroid glandb. Tropic hormoneb. Tropic hormonec. Controlled by hypothalamusc. Controlled by hypothalamus i. TRH—thyroid releasing hormonei. TRH—thyroid releasing hormone ii. Feedback inhibitionii. Feedback inhibition iii. GHIH also inhibitsiii. GHIH also inhibits

7. Adrenocorticotropic hormone (ACTH): 7. Adrenocorticotropic hormone (ACTH): a.a. Stimulates adrenal cortex to release cortico-Stimulates adrenal cortex to release cortico-steroid hormones (Glucocorticoids offset steroid hormones (Glucocorticoids offset effects of stress), effects of stress), b.b. Its release is controlled Its release is controlled by CRH (Corticotropin-releasing hormone: a by CRH (Corticotropin-releasing hormone: a hypothalamic hormone having a diurnal hypothalamic hormone having a diurnal rhythm) & rhythm) & c.c. Feedback inhibition: rising Feedback inhibition: rising glucocorticoids inhibit CRH secretionglucocorticoids inhibit CRH secretion

8. Gonadotropins: FSH and LH: 8. Gonadotropins: FSH and LH: a.a. Regulate Regulate gonads, gonads, b.b. FSH stimulates gamete production FSH stimulates gamete productionc.c. LH promotes production of gonadal hormones,LH promotes production of gonadal hormones, d.d. FSH and LH work in concert to cause follicle FSH and LH work in concert to cause follicle to mature (LH causes egg to be extruded from to mature (LH causes egg to be extruded from follicle), follicle), e.e. LH stimulates interstitial cells of LH stimulates interstitial cells of testes to produce testosterone, testes to produce testosterone, f.f. LH & FSH LH & FSH release is controlled by the hypothalamus release is controlled by the hypothalamus (GnRH) & (GnRH) & g.g. Negative feedback inhibition Negative feedback inhibition regulates FSH & LH releaseregulates FSH & LH release

9. Prolaction9. Prolactiona. Stimulates milk productiona. Stimulates milk productionb. PRH and PIH (serotonin and dopamine)b. PRH and PIH (serotonin and dopamine)c. Levels parallel those of estrogenc. Levels parallel those of estrogen

Posterior pituitary hormonesPosterior pituitary hormones

1. General characteristics1. General characteristicsa. ADH and oxytocin are comprised of 9 aa a. ADH and oxytocin are comprised of 9 aa (differ only in the identity of 2 residues)(differ only in the identity of 2 residues)b. Released in response to neural signals b. Released in response to neural signals from hypothalamusfrom hypothalamus

2. Oxytocin: 2. Oxytocin: a.a. Stimulates smooth muscle Stimulates smooth muscle contraction, contraction, b.b. Muscle response depends on Muscle response depends on number of oxytocin receptors in uterus and number of oxytocin receptors in uterus and breast (number of receptors increases during breast (number of receptors increases during pregnancy & afferent impulses as uterus pregnancy & afferent impulses as uterus stretches during pregnancy signals release of stretches during pregnancy signals release of oxytocin during late stages of pregnancy), oxytocin during late stages of pregnancy), c.c. Hormonal trigger for milk ejection & Hormonal trigger for milk ejection & d.d. Positive feedback mechanismPositive feedback mechanism

3. ADH (antidiuretic hormone): 3. ADH (antidiuretic hormone): a.a. Inhibits or Inhibits or prevents urine production, prevents urine production, b.b. In response to In response to increases in solute concentration, ADH is increases in solute concentration, ADH is released from hypothalamus (hypothalamus released from hypothalamus (hypothalamus has osmoreceptors), has osmoreceptors), c.c. ADH causes kidney ADH causes kidney tubules to reabsorb more water, tubules to reabsorb more water, d.d. At high At high doses, ADH causes vasoconstriction (Causes doses, ADH causes vasoconstriction (Causes increases systolic BP) & increases systolic BP) & e.e. Diabetes insipidus Diabetes insipidus (tasteless: deficiency in ADH secretion with (tasteless: deficiency in ADH secretion with output of huge amounts of urine & thirst)output of huge amounts of urine & thirst)

Thyroid glandThyroid gland

1. Structure1. Structurea. Two lobes connected by isthmusa. Two lobes connected by isthmusb. Follicles: Follicle cells produce thyroglobin b. Follicles: Follicle cells produce thyroglobin & lumen stores colloid (thyroglobin in & lumen stores colloid (thyroglobin in association with iodine)association with iodine)c. Thyroid hormone is derived from iodinated c. Thyroid hormone is derived from iodinated thyroglobinthyroglobind. Parafollicular cells produce calcitonind. Parafollicular cells produce calcitonin

2. Thyroid hormone (TH): 2. Thyroid hormone (TH): a.a. Two metabolically Two metabolically active iodine-containing hormones: thyroxine active iodine-containing hormones: thyroxine (T4) & triiodothyronine (T3), (T4) & triiodothyronine (T3), b.b. Thyroxine (T4) Thyroxine (T4) is produced by thyroid gland, is produced by thyroid gland, c.c. Triiodo- Triiodo-thyronine (T3) is formed at target tissue (T4 is thyronine (T3) is formed at target tissue (T4 is converted into T3), converted into T3), d.d. Increases metabolism in Increases metabolism in most tissues by stimulating glucose most tissues by stimulating glucose oxidation, oxidation, e.e. Increases adrenergic receptors Increases adrenergic receptors in blood vessels, in blood vessels,

f.f. Regulates tissue growth and development, Regulates tissue growth and development, g.g. T4 is bound to plasma proteins (TBG: T4 is bound to plasma proteins (TBG: thyroxine-binding globulin) & transported to thyroxine-binding globulin) & transported to target tissues(bind target tissue receptors, T3 target tissues(bind target tissue receptors, T3 is bound more readily, is bound more readily, h.h. Regulation: Falling Regulation: Falling levels trigger TSH release, rising levels of levels trigger TSH release, rising levels of thyroxine inhibits TSH release & conditions in thyroxine inhibits TSH release & conditions in which there is increased energy requirements which there is increased energy requirements causes TRH release from hypothalamuscauses TRH release from hypothalamus

3. Metabolic disturbances with thyroid gland 3. Metabolic disturbances with thyroid gland activity: activity: a.a. Myxedema: hypothyroid disorder Myxedema: hypothyroid disorder (if from lack of iodine, condition is endemic or (if from lack of iodine, condition is endemic or colloidal goiter, colloid is made but cannot be colloidal goiter, colloid is made but cannot be iodinated to make functional hormone, TSH iodinated to make functional hormone, TSH secretion increase to stimulateTH production, secretion increase to stimulateTH production, follicles accumulate more unuseable colloid), follicles accumulate more unuseable colloid),

b.b. Cretinism: hypothyroidism in infants (TH Cretinism: hypothyroidism in infants (TH replacement therapy prevents, cannot reverse replacement therapy prevents, cannot reverse effects), effects), c.c. Graves’ disease: Hyperthyroid Graves’ disease: Hyperthyroid pathology, autoimmune disease, abnormal pathology, autoimmune disease, abnormal antibodies that mimic TSH, exophthalmusantibodies that mimic TSH, exophthalmus

4. Calcitonin: a. Lowers blood calcium levels, 4. Calcitonin: a. Lowers blood calcium levels, b. Antagonist to the effect of parathyroid b. Antagonist to the effect of parathyroid hormone: Inhibits calcium release from bones hormone: Inhibits calcium release from bones by osteoclast activity & stimulates calcium by osteoclast activity & stimulates calcium uptake and incorporation, calcium acts as a uptake and incorporation, calcium acts as a humoral signal for calcitonin releasehumoral signal for calcitonin release

Parathyroid glandsParathyroid glands

1. Two pairs of glands in the posterior aspect 1. Two pairs of glands in the posterior aspect of the thyroid glandof the thyroid gland2. Chief cells (principal cells) secrete PTH: 2. Chief cells (principal cells) secrete PTH: parathyroid hormoneparathyroid hormone

3. Parathyroid hormone: 3. Parathyroid hormone: a.a. Controls Ca Controls Ca++++ balance, balance, b.b. Released in response to falling Released in response to falling blood Cablood Ca++++ levels, levels, c.c. PTH stimulates osteo- PTH stimulates osteo-clast activity (digest bone matrix & release clast activity (digest bone matrix & release CaCa++++ ), ), d.d. Enhances Ca Enhances Ca++++ reabsorption by reabsorption by kidney tubules, kidney tubules,

e.e. Increases Ca Increases Ca++++ absorption by intestine absorption by intestine (stimulates conversion of vitamin D into (stimulates conversion of vitamin D into active form), active form), f.f. Hyperparathyroidism is rare Hyperparathyroidism is rare (Ca(Ca++++ is leached from bones and replaced by is leached from bones and replaced by connective tissue, elevated blood Caconnective tissue, elevated blood Ca++++ asversely affects NS and contributes to asversely affects NS and contributes to formation of kidney stones as excess Caformation of kidney stones as excess Ca++++ is is deposited in kidney tubules), deposited in kidney tubules), g.g.Hypoparathyr-Hypoparathyr-oidism: PTH deficiency following injury or oidism: PTH deficiency following injury or surgical removal (increased NS excitability)surgical removal (increased NS excitability)

Adrenal glandsAdrenal glands

1. Two endocrine glands: 1. Two endocrine glands: a.a. Adrenal medulla Adrenal medulla (acts as part of the sympathetic NS) & (acts as part of the sympathetic NS) & b.b. Adrenal cortexAdrenal cortex2. Response to stressful conditions2. Response to stressful conditions3. Adrenal cortex: 3. Adrenal cortex: a.a. Corticosteroids (steroids, Corticosteroids (steroids, more than two dozen, synthesized from more than two dozen, synthesized from cholesterol), cholesterol),

b.b. Mineralocorticoids (type of corticosteroid: Mineralocorticoids (type of corticosteroid: Regulate electrolyte concentrations in extra-Regulate electrolyte concentrations in extra-cellular fluid, aldosterone is most abundant, it cellular fluid, aldosterone is most abundant, it reduces excretion of sodium from the body, reduces excretion of sodium from the body, stimulates reabsortion of sodium in the distal stimulates reabsortion of sodium in the distal tubule of kidney), tubule of kidney), c.c.4 Mechanisms controlling 4 Mechanisms controlling aldosterone secretion aldosterone secretion

i. Renin-angiotensin mechanism: JGA release i. Renin-angiotensin mechanism: JGA release renin in response to BP decrease, initiates renin in response to BP decrease, initiates cascade forming angiotensin II formation, cascade forming angiotensin II formation, which stimulates aldosterone release from which stimulates aldosterone release from adrenal cortex,ii. Direct stimulation by plasma adrenal cortex,ii. Direct stimulation by plasma sodium and potastium ions, iii. ACTH: at very sodium and potastium ions, iii. ACTH: at very high levels of ACTH, aldosterone secretion is high levels of ACTH, aldosterone secretion is increased, iv. ANP: Atrial natriuretic peptide: increased, iv. ANP: Atrial natriuretic peptide: when BP is high, heart release ANP to inhibit when BP is high, heart release ANP to inhibit renin and aldosterone secretionrenin and aldosterone secretion

d.d. Glucocorticoids (type of corticosteroid): Glucocorticoids (type of corticosteroid): i.i. Influence metabolism and mediate response Influence metabolism and mediate response to stress, to stress, ii.ii. Cortisol, cortisone,corticosterone Cortisol, cortisone,corticosterone iii.iii.Only cortisol secreted in significant amount Only cortisol secreted in significant amount iv.iv. Non-stress: CRH, ACTH, cortisol release, Non-stress: CRH, ACTH, cortisol release, negative feedback, negative feedback, v.v. Stress: Sympathetic NS Stress: Sympathetic NS overrides inhibitory effect of elevated cortisol overrides inhibitory effect of elevated cortisol levels & triggers CRH release, levels & triggers CRH release, vi.vi. Gluconeo- Gluconeo-genesis: Conversion of fats into glucosegenesis: Conversion of fats into glucose

e.e. Cushing’s disease: excess cortisone: Cushing’s disease: excess cortisone: i.i. Characterized by persistent hyperglycemia Characterized by persistent hyperglycemia (steroid diabetes), (steroid diabetes), ii.ii. Loss of muscle & bone Loss of muscle & bone protein, protein, iii.iii. Water & salt retention, Water & salt retention, iv.iv. “moon” “moon” face, face, v.v. Redistribution of body fat ( Redistribution of body fat (e.g.,e.g., buffalo buffalo hump), hump), vi.vi. Anti-inflammatory effects mask Anti-inflammatory effects mask infectioninfection

f.f. Addison’s disease: hyposecretory disorder Addison’s disease: hyposecretory disorder of adrenal cortex: of adrenal cortex: i.i. Weight loss, Weight loss, ii.ii. Reduced Reduced plasma glucose & sodium levels, plasma glucose & sodium levels, iii.iii. Severe Severe dehydration & hypotension, dehydration & hypotension,

g.g.Gonadocorticoids(Sex hormones): primarily Gonadocorticoids(Sex hormones): primarily androgens: androgens: i.i. Androstenedione converted to Androstenedione converted to testosterone & dihydrotestosterone, testosterone & dihydrotestosterone, ii.ii. Small Small amounts of estrogens, amounts of estrogens, iii.iii. Adrenal cortex sex Adrenal cortex sex hormones is only fraction of gonadal sources, hormones is only fraction of gonadal sources, iv.iv. Possible role in onset of puberty (levels Possible role in onset of puberty (levels rise during years preceding onset)rise during years preceding onset)

4. Adrenal medulla (AM): 4. Adrenal medulla (AM): a.a. Chromaffin cells Chromaffin cells (Modified postgang. sympathetic neurons that (Modified postgang. sympathetic neurons that secrete epinephrine & NE), secrete epinephrine & NE), b.b. Initial response Initial response to stress is mediated by sympathetic NS, to stress is mediated by sympathetic NS, c.c. Activation of AM & associated release of EPI Activation of AM & associated release of EPI & NE prolong sym. response (High BP & HR, & NE prolong sym. response (High BP & HR, mobilization of glucose&shunt blood from GI)mobilization of glucose&shunt blood from GI)

PancreasPancreas

1. Contains both exocrine (GI enzymes) & 1. Contains both exocrine (GI enzymes) & endocrine cellsendocrine cells2. Pancreatic islets (islets of Langerhans)2. Pancreatic islets (islets of Langerhans)a. Two populationsa. Two populations i. Alpha cells—produce glucagonsi. Alpha cells—produce glucagons ii. Beta cells—produce insulinii. Beta cells—produce insulin

3. Effects: Insulin: hypoglycemic hormone & 3. Effects: Insulin: hypoglycemic hormone & Glucagon: hyperglycemic hormoneGlucagon: hyperglycemic hormone4. Glucagon effects:4. Glucagon effects:a.a. Breakdown of glycogen Breakdown of glycogen to glucose (glyconeogenesis), to glucose (glyconeogenesis), b.b. Synthesis of Synthesis of glucose from lactic acid, fatty acids & amino glucose from lactic acid, fatty acids & amino acids, acids, c.c. Release of glucose from liver Release of glucose from liver5. Regulation of glycogen: Humoral response 5. Regulation of glycogen: Humoral response to decreased blood glucoseto decreased blood glucose

6. Insulin effects: 6. Insulin effects: a. a. Lower blood glucose Lower blood glucose ( enhance membrane transport of glucose into ( enhance membrane transport of glucose into body cells), body cells), b.b. Alter protein & fat metabolism, Alter protein & fat metabolism, c.c. Inhibits breakdown of glycogen, Inhibits breakdown of glycogen, d.d. Triggers Triggers enzymatic activity (oxidation of glucose for enzymatic activity (oxidation of glucose for ATP production, synthesis & storage of ATP production, synthesis & storage of glycogen, conversion of glucose to fat & its glycogen, conversion of glucose to fat & its storagestorage

7. Regulation of insulin: Humoral response to 7. Regulation of insulin: Humoral response to increased circulating glucoseincreased circulating glucose8. Diabetes mellitus (DM): Hyposecretion or 8. Diabetes mellitus (DM): Hyposecretion or hypoactivity of insulin: hypoactivity of insulin: a.a. Excessive hyper- Excessive hyper-glycemia triggers sym. response (activates glycemia triggers sym. response (activates systems associated with hypoglycemia),systems associated with hypoglycemia),b.b. Lipidemia: Lipidemia: i.i. Fats mobilized to use as Fats mobilized to use as cellular food, cellular food, ii.ii. FA metabolites accumulate as FA metabolites accumulate as ketone bodies, ketone bodies, iii.iii. Bd pH drops (ketoacidosis), Bd pH drops (ketoacidosis),

c.c. Signs of DM: Signs of DM: i.i. Polyuria, Polyuria, ii.ii. Polydipsia & Polydipsia & iii.iii. Polyphagia, Polyphagia, d.d. Polyuria: Polyuria: i.i. Excessive glucose Excessive glucose in kidney filtrate acts as a diuretic (in kidney filtrate acts as a diuretic (i.e.,i.e., inhibits inhibits water reabsortion), water reabsortion), ii.ii. Increased urine output Increased urine output causes dehydration & decreased Bd volume, causes dehydration & decreased Bd volume, iii.iii. Electrolyte loss with excretion of excess Electrolyte loss with excretion of excess ketones (- charged), ketones (- charged), e.e.Polydipsia: dehydration Polydipsia: dehydration stimulate thirst center in brain, stimulate thirst center in brain, f.f. Polyphagia: Polyphagia: i.i. Glucose cannot be used because it cannot Glucose cannot be used because it cannot be absorbed by cells, be absorbed by cells, ii.ii. Results in hunger Results in hunger

9. Types of DM: 9. Types of DM: Type IType I: Insulin dependent DM : Insulin dependent DM (IDDM), autoimmume destruction of (IDDM), autoimmume destruction of ββ cells, cells, juvenile onset, lack insulin activity, long term juvenile onset, lack insulin activity, long term cardiovascular & neural problemscardiovascular & neural problemsType IIType II: Non-insulin dependent DM (NIDDM), : Non-insulin dependent DM (NIDDM), usually after the age of 40, 90% of DM cases, usually after the age of 40, 90% of DM cases, most patients are overweight, genetic link, most patients are overweight, genetic link, insulin is produced in inadequate quantities insulin is produced in inadequate quantities or with faulty receptorsor with faulty receptors

GonadsGonads

1. Same sex hormones as those produced by 1. Same sex hormones as those produced by adrenal cortexadrenal cortex2. Ovaries produce estrogens & progesterone2. Ovaries produce estrogens & progesterone(sexual maturation & menstrual cycle)(sexual maturation & menstrual cycle)3. Testes produce testosterone (sexual 3. Testes produce testosterone (sexual maturation & sex drive)maturation & sex drive)4. Release of gonadal hormones is regulated 4. Release of gonadal hormones is regulated by gonadotropinsby gonadotropins

Pineal glandPineal gland

1. Floor of 3rd ventricle within diencephalons1. Floor of 3rd ventricle within diencephalons2. Primary secretory product is melatonin2. Primary secretory product is melatonin3. Pineal gland receives indirect inputs from 3. Pineal gland receives indirect inputs from visual systemvisual system4. SCN has melatonin receptors4. SCN has melatonin receptors

ThymusThymus

1. Large in children, decreases with age1. Large in children, decreases with age2. Hormonal products important for T cell 2. Hormonal products important for T cell maturation (thymopoietins & thymosins)maturation (thymopoietins & thymosins)