The Endocrine System

1. The Endocrine System

2. Electrochemical Signals • Influences metabolic activities by means of hormones • Chemical messengers released into the bloodstream to be transported throughout the body. • Lag time in response • Nervous = (near) immediate • Endocrine = seconds to days • Once initiated, hormonal responses tend to be more prolonged than nervous responses • Study of hormones & endocrine organs = endocrinology

3. Processes controlled by Hormones • Reproduction • Growth & development • Mobilizing body’s defense against stressors • Maintaining electrolyte balance • Maintaining nutrient balance • Regulating cellular metabolism • Maintaining an available energy source

4. Overview • Endocrine glands, compared to other systems: • Called glands – main purpose: secrete • Small glands, less than 2lbs worth • Widely scattered throughout the body – usually near their target organs • Endocrine vs. exocrine • Exocrine – have ducts • Non hormonal products are routed to a membrane surface • Endocrine – ductless • Release hormones into surrounding tissue of organs that are richly vascular • Easy to be released into bloodstream of the appropriate organ. • Most are physically arranged into branching networks to maximize the spread of hormones

5. Endocrine Glands • Pituitary • Thyroid • Parathyroid • Adrenal • Pineal • Thymus • Organs that contain endocrine tissue & produce hormones • Pancreas • Gonads (testes & ovaries) • Neuroendocrine organ = hypothalamus

6. Chemistry of Hormones • Hormones are chemical substances, secreted by cells into extracellular fluids, that regulate the metabolic function of other cells in the body. • 2 classes: amino-acid based vs. steroid • Most hormones are amino-acid based • Simple derivates: amines, thyroxine, peptides • Steroid hormones are synthesized from cholesterol • Gonadal & adrenocortical hormones • “3rd” class: eicosanoids • Leukotrienes & prostaglandins • Local hormones: very specific functions • Leukotrienes: mediate inflammation & slow allergic reactions • Prostaglandins: raising BP, increases birth contractions of the uterus

7. Mechanisms of Hormone Action • Hormones act on target cells by altering cell activity. • Increase or decrease rates of normal cellular activity • Precise response depends on the target cell • Hormonal stimulus should produce one of the following changes • Alters permeability of the plasma membrane by opening/closing ion channels • Stimulates synthesis of proteins or regulatory molecules (like enzymes) within the cell • Activiates/deactivites enzymes • Induces secretory activity • Stimulates mitosis

8. Hormone – Target Cell Specificity • Each hormone only can only work on certain tissues • Specific protein receptors on a cell membrane will only receive the chemical message from certain hormones • EX) Adrenocorticotrophic hormone (ACTH) receptors are only found on the adrenal cortex, where as thyroxine receptors are found on nearly all cells of the body. • 3 important factors to ensure proper target cell activiation • Consistent blood levels of hormone • Relative number of receptors for that hormone on/in the target cells • The affinity (strength) of the bond between the hormone and the receptor

9. Hormone Receptors • Receptors are dynamic structures • Will change in response to need • In response to rising blood levels of hormone, more receptors will be created – up-regulation • Prolonged exposure to high levels of a hormone could cause desensitization of receptors, so receptors will respond less vigorously to hormones – down-regulation • Hormones don’t always affect their own targets, but how they respond to other receptors • EX) Progesterone reduces estrogen receptors in the uterus • Estrogen causes the same cells to produce more progesterone receptors – enhancing the ability to respond to progesterone.

10. Half-Life, Onset & Duration of Hormone Activity • Hormones are potent • Profound effects in very low concentrations • Concentration of a circulating hormone at any time reflects • Its rate of release • Speed of its inactivation and removal from the body • Some hormones are rapidly degraded by enzymes • Most are removed from the blood by the kidney/liver enzymes • Breakdown products of hormones released mostly in urine (rarely in feces) • How long a hormone stays in the blood is its half-life • Ranges from fraction of seconds – 30 minutes • Most hormones effects are seen immediately, but steroid hormones require hours, sometimes days before their effects are seen. • Some hormones, like testosterone, are secreted in an inactive form, and must be activated, when ready, by the target organ • Duration of hormone in bloodstream ranges from 20 minutes – hours • Hormone levels are precisely controlled to maintain consistent levels while the body is continuously changing

11. Control of hormone release • Negative feedback • As hormone levels rise, they activate the target cells • Once the desire effect is achieved, hormone production will be inhibited further. • As a result, hormone blood levels vary only within a narrow “desirable” range.

12. Hormonal Stimuli • Stimuli: Humoral, Hormonal, or Neural • Humoral: hormones released in response to nutrition/ionic needs • Ex) The parathyroid detects low blood calcium, initiates the secretion of PTH (which stimulates the uptake of calcium from bones), thus raising blood calcium • Once blood calcium levels have stabilized, the production of PTH ceases • Other examples include the body’s use of insulin (sugars) & aldosterone (maintains sodium balance)

13. Neural & Hormonal Stimuli • Neural: nerve fibers stimulate the release of hormones • Sympathetic nervous system • Adrenal medulla releases epinephrine during periods of stress • Hormonal: Many endocrine glands release their hormones in response to other hormones • The hypothalamus-pituitary relationship is the core of the study of endocrinology • Hypothalamus release hormones to regulate and inhibit the pituitary, in turn… • The function of most anterior pituitary hormones is to initiate the release of other endocrine hormones (targeted organs) • Once those target hormones have been triggered, they will inhibit the production of more pituitary hormones

14. Neural Modulation • “On” and “off” factors • Hormonal, humoral & neural stimuli initiate the production of hormones • Negative feedback inhibit the overproduction of hormones • The nervous system can “override” the fairly strict functioning of the nervous system • Ex) During periods of stress, blood sugar levels rise because the hypothalamus and sympathetic nervous system are strongly activated • This ensures the body has enough fuel for more vigorous activity • The endocrine system would usually response to the increased sugar by?

15. Major Endocrine Organs: Pituitary Gland • Nestled in the sellaturcica of the sphenoid bone • About the size and shape of a pea on a stalk • The stalk, that connects to the hypothalamus is called the infundibulum(funnel shaped) • Two lobes: • Posterior Lobe - neurohypophysis • Neural tissue – nerve fibers & glia-like supporting cells • Releases neurohormones it receives from the hypothalamus • Not a true endocrine gland – just stores hormones from hypothalamus • Anterior Lobe - adenohypophysis • Completely glandular tissue • Releases numerous hormones

16. Pituitary Hypothalamic Relationship • Posterior lobe of the pituitary is actually part of the brain. • Downgrowth of hypothalamic (neural) tissue runs through the infundibulum • Two hormones are synthesized here: • Oxytocin & ADH (antidiuretic hormone) • All hypothalamic regulatory hormones are amino-acid based.

17. Structural/Functional relationships of the pituitary and the hypothalamus

18. Anterior Pituitary Hormones • Usually called the “master gland” • Produces many hormones, including most hormones that regulate other hormones • 6 distinct adenophyophyseal hormones • Creates POMC – pro-opiomelanocortin • A pro-hormone • Building block hormone – used to create many different molecules • Natural opiates – like endorphins • Melanocytes – break down melanin • 4 out of 6 of the distinct hormones are trophichormones • Regulate the secretion of other endocrine glands • TSH, ACTH, FSH, & LH

19. Growth Hormone • Anabolic steroid hormone • Stimulates most body cells to increase in size and divide • Major targets are bones and skeletal muscles • Stimulation along the epiphyseal plate leads to long bone growth • Promotes the creation of muscle mass in skeletal muscles • GH promotes protein synthesis • Encourages the use of fats for fuel, thus conserving glucose • Stimulates the uptake of amino acids from the blood and their incorporation into cellular proteins throughout the body • Stimulates the uptake of sulfur (needed to synthesize chondrotin sulfate) – helps form cartilage

20. Growth Hormone • Works via negative feedback, like all hormones • Secondary stimulation • Stress, nutritional factors, and sleep patterns • Highest levels during evening sleep • Highest total amounts during adolescene and then declines with age. • Secondary inhibition • Hyperlipidemia, hyperglycemia, obesity, emotional deprivation • Hyposecretion: • Pituitary dwarfism in children • Hypersecretion • Gigantism in children; acromegaly in adults

21. TSH: Thyroid Stimulating Hormone • TSH – thyrotropin • Stimulated by TRH (thyrotropin-releasing hormone) – a hypothalamic peptide • Pregnancy & cold temperatures can indirectly increase the production of TSH • Stimulates normal development and secretory activity of the thyroid gland • Rising blood levels of thyroid hormones will inhibit the further production of TSH • The hypothalamus will release somatostatin which will further inhibit the production of TSH • Hypersecretion: cretinism in children, myxedema in adults • Causes low thyroxine • Hyposecretion: Graves’ disease • Causes high thyroxine

22. ACTH: Adrenocorticotropic Hormone • Stimulates adrenal cortex to release corticosteroid s • This, in turn, releases glucocorticoids • Most importantly – helps the body resist stressors • ACTH release has a daily rhythm – peaks in early morning • Triggers for increase beyond normal limits include: • Fever • Hypoglycemia • Stressors of all types • Inhibited by the release of glucocorticoids • Hyposecretion: rare & idiopathic • Hypersecretion: Cushing’s disease

23. Gonadotropins • Follicle-stimulating hormone (FSH) & LH • Present in both males & females! • Regulate the functions of gonads • FSH stimulates gamete production • LH promotes production of gonadal hormones • In females, LH works with FSH to cause maturation of a follicle (immature egg) = ovulation • Promotes the synthesis of estrogen & progesterone • In males, LH stimulates interstitial cells to produce testosterone • LH is called ICSH in makes – interstitial cell-stimulating hormone

24. Gonadotropins • Absent in the blood of prepubertal boys & girls • When puberty starts, the anterior pituitary produces gondaotrope cells (building block of gonadotropins) – causing the gonads to mature • The hypothalamus produces GnRH – which promotes the production of FSH & LH • The gonadal hormones (estrogen, progesterone, & testosterone) suppress/inhibit the further production of FSH & LH • Hyposecretion: Failure to sexually mature • Hypersecretion: No important effects

25. Prolactin • PRL – protein hormone/similar to growth hormone • Produces by lactotropes – stimulates the gonads of some mammals • Well-documented – production of breastmilk • Evidence that PRL enhances testosterone production • PRH released by hypothalamus to stimulate prolactin production • PIH (Prolactin-inhibiting hormone) IS dopamine – prevents prolactin secretion • In males, PIH predominates, but in women, prolactin levels rise and fall with estrogen levels • Low estrogen stimulates PIH release & high estrogen promotes more prolactin production

26. Prolactin • Brief rise in prolactin levels accounts for breast tenderness & swelling just before menstruation • Since the PRL production is so brief, no milk is produced • In pregnancy, prolactin rises dramatically in the last trimester and milk production begins • Fun fact: prolactin levels can remain high as much as two years after breastfeeding ceases. • Hyposecretion: poor milk production in nursing women • Hypersecretion: Galactorrhea, cessation of mense in females, impotence and gynecomastia in males

27. Posterior Pituitary Hormones • Comprised largely of axons of hypothalamic neurons • Stores oxytocin & antidiuretic hormone (ADH) • These hormones are left “on demand”, when stimulated by nerve impulses from the hypothalamus • ADH & oxytocin are protein based hormones • Almost identical molecularly • VERY different functionally • ADH influences water balance • Oxytocin stimulates the contraction of smooth muscle

28. Oxytocin • Released in significantly high amounts during childbirth & nursing women • Oxytocin receptors peak near the end of pregnancy. • Stretching of the uterus and cervix as birth approaches sends sensory impulses directly to the hypothalamus • Hypothalamus makes more oxytocin and raises the blood level of oxytocin • Higher blood levels of oxytocin – expulsive contractions of labor gain momentum & end with labor • Oxytocin triggers milk ejection (“let down”) in women whose breasts actively produce milk in response to prolactin • Positive feedback – as demand for milk increases, MORE oxytocin is released, instead of being inhibited

29. Oxytocin • Synthetic oxytocin – Pitocin – can be used to artificially progress labor • Less frequently, oxytocics given to stop uterine/vaginal bleeding post-delivery • In non-lactating females, the non-pregnant & males: • Potent peptide plays a role in sexual arousal, when the body is primed for reproduction • Responsible in satisfaction in the sexual interaction • Overall, it is now readily known as the “attachment” hormone.

30. Antidiuretic Hormone (Vasopressin) • Diuresis: urine production • ADH: Inhibits or prevents urine formation • Prevents wide swings in water balance • Helps to avoid water overload or water dehydration • Hypothalamic neurons called osmoreceptors continually monitor solute & water concentration of the blood • When solutes make blood too concentrated • Ex) excessive perspiration, inadequate liquid intake, repeated vomitting • Osmoreceptors transmit excitatory impulses to the hypothalamic neurons to release ADH • This will tell the kidneys to reabsorb water into the bloodstream and produce less urine • When solute concentration declines, osmoreceptors are depolarized, stopping ADH production • ADH can also be triggered by pain, low blood pressure, and certain drugs: nicotine, morphine and barbiturates (mild sedation to anesthesia)

31. ADH - Vasopression • Hyposecretion: Diabetes insipidus •  Characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine. • Drinking alcohol inhibits ADH = copious urine output • “hangover” – dehydrating effect of alcohol consumption from suppression of ADH production • Diuretic drugs antagonize the effects of ADH and cause water to be flushed from the body • Used to manage hypertension, edema (retention of fluids in tissues), typical in congestive heart failure • In high concentrations – ADH causes vasoconstriction – raising BP • Helpful in situations like severe blood loss

32. Thyroid Gland • Butterfly shape gland in the anterior neck, just inferior to the larynx, on the trachea • Two lobes – connected by isthmus (piece of tissue) • Internally: • Composed of hollow, spherical follicles • Cuboidal & squamous cells – produce thyroglobulin • Central cavity produces colloid, amber sticky material that stores iodine • Parafollicular cells: produce calcitonin

33. TH – thyroid hormone • TH – major metabolic hormone – iodine containing hormones: 2 types: • T4: thyroxine • Secreted by thyroid follicle • T3: triiodothyronine: • Converted by target organs from T4 • TH effects EVERYTHING except • The brain • Spleen • Testes • Uterus • Thyroid itself • In every cell of the body, T4 & T3 – stimulates glucose oxidation • Thus, increasing basal metabolic rate& body’s heat production

34. Transport & Regulation of T4 & T3 • T4 & T3 bind to TBGs (thyroid binding globulins – transport proteins in the blood) produced by the liver • Then, T4 & T3 bind to target receptors in various tissues • T3 binds more avidly & is 10x more active • Most tissues have enzymes to convert T4 to T3 • Falling thyroxine blood levels trigger the release of TSH, and ultimately, thyroxine

35. Hyposecretion of T4 & T3 • BMR rate below normal • Decreased body temperature/cold intolerance • Decreased appetite; weight gain • Decreased glucose metabolism • Elevated cholesterol/triglyceride levels • In infants: • Slowed/deficient brain development, retardation • Growth retardation, retention of child’s body proportion • In adults: • Mental dulling, depression, paresthesias, memory impairment, hypoactive reflexes • Decreased efficency of pumping action of the heart • Low heart rate and low blood pressure • Sluggish muscle action/cramps • Depressed GI motility, constipation • Depressed ovarian function • Sterility • Depressed lactation • Skin pale, thick, dry facial skin, coarse and thick hair

36. Hypersecretion of T4 & T3 • BMR above normal • Increased body temperature and heat intolerance • Increased appetite & weight loss • Loss of muscle mass • Irritability, restlessness, insomnia, personality changes • Rapid heart rate and palpitations, high blood pressure • Dangerous condition – can lead to heart failure • Muscle atrophy and weakness • In children: accelerated long bone growth but then early epiphyseal plate closure & short stature • Excessive GI motility, diarrhea • Depressed ovulation • Skin flushed, thin, and moist, hair is fine & soft, nails soft & thinning

37. Calcitonin • Polypeptide hormone produced by parafollicular cells • Lowers blood calcium • Direct antagonist to parathyroid hormone (PTH) which raises blood calcium • Targets the skeleton • It inhibits osteoclast activity • Stimulates calcium uptake and incorporation into the bone matrix • Excessive blood calcium (over 20%) act as a humoral stimulus for calcitonin release • An extremely rapid process • In children, calcitonin plays important role when skeleton is growing quickly • In adults – weak hypocalcemic agent

38. Parathyroid Glands • Usually 4 glands on the posterior aspect of the thyroid gland • The parathyroid’s glandular cells are arranged in thick branching cords containing oxyphil cells and large numbers of chief cells • Chief cells – secrete PTH – parathyroid hormone • PTH – protein hormone • Triggered by falling blood calcium levels • Inhibited by hypercalcemia • 3 target organs • Skeleton, kidneys & intestines

39. PTH • Stimulates osteoclasts to digest some bony matrix to increase blood calcium concentration • Enhances reabsorption of calcium by the kidneys • Increases absorption of calcium by intestinal mucosal cells • Enhanced by PTH’s vitamin D activation – better calcium absorption • For Vitamin D to work, the kidneys must turn it into calcitriol – this is stimulated by the production of PTH • Stable calcium levels are important for: • Nerve impulses, muscle contractions, blood clotting • Hyposecretion: tetany, spasms of the larynx, respiratory paralysis, death

40. Adrenal (Suprarenal) Glands • Pyramid shaped organs perched atop the kidneys – cushioned in fat • Two glands in one • Adrenal medulla – more like nervous tissue than a gland • A part of the sympathetic nervous system • Adrenal cortex – bulk of glandular tissue • Encapsulates the medulla • Medulla & cortex produce different hormones • Both sets of hormones help cope with “extreme” (stressful) situations • Adrenal glands

41. Adrenal Cortex • Synthesized from cholesterol – about 24 steroid hormones are collectively called corticosteroids • Mineralocorticoids • Regulation of electrolyte concentration (mineral salts: sodium & potassium) • Sodium is essential for homeostasis • Excessive sodium intake and retention cause high BP • Aldosterone – 95% mineralocorticoids produced • Maintaining sodium balance is primary goal • Reduces excretion of sodium from body • Target: distal tubules of kidneys – stimulates reabsorption of sodium ions from forming urine into the bloodstream

42. Aldosterone • Aldosterone also enhances sodium reabsorption from perspiration, saliva & gastric juice • Crucial for maintaining normal blood flow & BP • Aldosterone’s effects are brief (about 20 mintues) • Therefore, electrolyte balance can be precisely controlled and monitored continually • Secretion stimulated by: • Rising blood levels of potassium • Decreasing blood volume • Decreasing BP • Reverse conditions inhibit aldosterone secretion

43. Aldosterone • Hypersecretion: aldosteronism: results from adrenal neoplasms • Neoplasms = growths (both malignant & benign) • Problems that arise: edema, accelerated excretion of potassium ions • Extreme potassium loss – neurons are unresponsive, muscle weakness/paralysis may occur • Hyposecretion: Addison’s disease • Results from deficient mineralocorticoid & glucocorticoid release

44. Regulation of Aldosterone • Renin-angiotensin system • Major regulator of aldosterone • Specialized cells in the kidneys become “excited” when blood pressure/blood volume drops • Kidneys release renin into the bloodstream • Renin reacts with angiotensinogen • Triggers an enzymatic cascade reaction to produce angiotensin II • Angiotensin II stimulates aldosterone to be released by the adrenal cortex • Angiotensin II has widespread effects on BP • Plasma concentrations of sodium & potassium • Increased potassium & decreased sodium are stimulatory • Opposite conditions are inhibitory

45. Regulation of Aldosterone • ACTH • Under normal circumstances ACTH has little to no effect on aldosterone release • SEVERE STRESS: hypothalamus secretes CRH (corticotropin- releasing hormone) • This steps up the secretion of aldosterone a little • The rise in blood pressure/volume helps ensure adequate delivery of nutrients and respiratory gases during the stressful period • ANP (Atrialnatriuretic peptide) • Natriurietic = produce salty urine • Hormone secreted by the heart • Fine tunes blood pressure and sodium/water balance • Major effect: inhibits renin-angiotensin mechanism • Overall effect – decrease blood pressure by allowing sodium * water to flow out of the body in urine

46. Glucocorticoids • Influence metabolism of most body cells & help resist stressors • Normal circumstances: help body maintain fairly constant/stable sugar levels when food intake is intermittent • Also maintains blood volume by preventing water shifting into tissues • Severe stress (such as hemorrhage, infections, physical/emotional trauma) • Dramatically higher output of glucocorticoids – help body negotiate crisis • Cortisol, cortisone & corticocosteroneare glucocorticoids • Cortisol is secreted in most significant amounts

47. Glucocorticoid secretion • Cortisol release is triggered by CRH, which promotes ACTH release • Rising cortisol levels inhibit CRH release and shut off ACTH • Cortisol bursts happen in a regular pattern daily • Based on eating and activity patterns • Peak shortly after waking in the morning, lowest just before sleep and shortly after sleep ensues • Sympathetic nervous impulses can override inhibitory effects of rising cortisol levels • The resulting increase in ACTH causes an outpouring of cortisol from the adrenal cortex.

48. Stress & Glucocorticoids • Stress results in dramatic rise in glucose, fatty acids & amino acids – all provoked by cortisol • Primary metabolic effect – gluconeogenesis • Creation of glucose from non-carbohydrate molecules • To “save” glucose for the brain, cortisol mobilizes fatty acids from adipose tissue and encourages use for energy • Enhances epinephrine’s vasoconstrictive effects • Rise in BP & circulatory efficiency helps ensure nutrients are delivered quickly to cells

49. Glucocorticoids • Ideal amounts of glucocorticoids promote normal function • However: • Excessive glucocorticoids: • Depress cartilage and bone formation • Inhibit inflammation & prevent vasodilation • Depress the immune system • Promote changes in cardiovascular, gastrointestinal and neural functioning

50. Hypersecretion & Hyposecretion • Hypersecretion helps treat chronic inflammatory diseases like RA, or allergic responses • May relieve some symptoms, also causes undesirable effects • Cushing’s disease: • Causes: ACTH tumor in pituitary, malignancy in lungs, pancreas, kidneys or tumor of the adrenal cortex • Most often: pharmacological doses of glucocorticoids (steroids) • Characterized by persistent hyperglycemia, dramatic loss in muscle mass, water/salt retention, leading to hypertension & edema • Hyposecretion: Addison’s disease • Weight loss, glucose & sodium levels drop & potassium rises • Severe dehydration & hypotension is common