1 Water Soluble HormonesFast acting hormones – affect depends on 2nd messenger, not hormone Signal amplification – hormones that stimulate synthesis of 2nd messengers can produce an almost instantaneous response because they influence existing enzymes; each receptor produces 1000s of 2nd messengers, leading to a cascade effect & ultimately amplification of hormonal signal Signal Amplification

2 Lipid Soluble HormonesSlow acting hormones – requires intracellular receptor Increases or decreases synthesis…

3 Heads Up I am obviously not Steve

4 The Pea Sized Pituitary a.k.a. ‘Hypophysis’TWO lobes Anterior pituitary (Adenohypophysis) – 7 hormones Glandular tissue – produces hormones in situ (by specific cell) Posterior pituitary (Neurohypophysis) – 2 hormones Hormones produced in hypothalamus  transported via nerve cell to pituitary diencephalon  ‘infundibulum’  pituitary

5 Pro-opiomelanocortin - The ProhormonePOMC – large precursor molecule of anterior pituitary Enzymatic Breakdown Products Include Adrenocorticotropic hormone (ACTH) 2 natural opiates – enkephaline & beta endorphin Melanocyte-stimulating hormone (MSH)

6 Anterior Pituitary HormonesHormones – 6 distinct but two of prohormone origin Growth hormone (GH) Thyroid-stimulating hormone (TSH) or thyrotropin – tropic Adrenocorticotropic hormone (ACTH) – prohormone origin tropic Follicle-stimulating hormone (FSH) – tropic Luteinizing hormone (LH) - tropic Prolactin (PRL) Melanocyte stimulating hormone (MSH) – prohormone origin TROPIC = affects activity of other endocrine glands

7 Hypothalamus & Anterior Pituitary RelationshipA.K.A. Adenohypophysis ‘glandular undergrowth’ Hypothalamus hormones travel through delivery system to anterior pituitary ‘portal system’ Negative feedback allows control…

8 Understanding The Endocrine System Health VS DiseaseHormones are ‘Just’ chemicals… The Goldie Locks Rule!!! Too Much Hormone Just Right Hormone Level Too Little Hormone

9 Growth Hormone (GH) Stimulates most cells, but esp. bone & skeletal muscle Promotes protein synthesis & fat mobilization Most effects are mediated indirectly by insulin-like growth factors (IGFs) Hypothalamus has regulatory role over A.P. hormone release!!! IGFs are a family of growth-promoting proteins produced by liver, skeletal muscle, bone & other tissues. IGFs from liver act as hormones, others act locally within those tissues. IGFs stimulate uptake of nutrients from blood & incorporation into proteins & DNA allowing growth by cell division. They also act to form collagen & deposition of bone matrix. GHIH – growth hormone-inhibiting hormone (somatostatin)

10 Homeostatic Imbalances of Growth HormoneHypersecretion Children – gigantism Adults – acromegaly Hyposecretion Children – pituitary dwarfism Adults – Simmond’s disease

11 Thyroid-Stimulating Hormone (Thyrotropin)Basic Function Summary of Regulation Stimulates the normal development and secretory activity of the thyroid Regulation of TSH release Stimulation = thyrotropin-releasing hormone (TRH) Inhibition = thyroid hormones  2 impacts Packet calls it ‘thyroid releasing factor’ – TRF ‘Endocrine’ pg 11

12 Adrenocorticotropic Hormone (Corticotropin)Stimulates the adrenal cortex to release corticosteroids Regulation of ACTH release Hypothalamus releases corticotropin-releasing hormone (CRH) in a daily rhythm Fever, hypoglycemia, and stress can alter the release of CRH

13 Gonadotropins – ‘Stimulate Gonads’FSH – follicle stimulating hormone LH – lutenizing hormone Regulation of Gonadotropin Release FSH stimulates gamete (egg or sperm) production LH stimulates ovulation & corpus luteum formation in women, & production of sperm in men Both absent in blood prepuberty…

14 Prolactin PRL PRL primarily controlled via inhibitory hormoneStimulates milk production Blood levels rise toward the end of pregnancy Suckling stimulates PRL release and promotes continued milk production Secreted in men, no apparent function PRL primarily controlled via inhibitory hormone

15 Melanocyte Stimulating HormoneMSH Hormonal Control of Energy Balance Stimulates melanocytes to synthesize & deposit melanin NOT important in humans Agouti-related peptide (AgRT), CRH, corticotropin releasing hormone, MCH – melanin-concentrating hormone, alpha MSH = melanocyte-stimulating hormone, NPY – neuropeptide Y, orexins, orexigenic peptides, POMC – pro-opiomelanocortin, PYY peptide YY, TRH – thryotropin releasing hormone Acts as CNS neurotransmitter involved in control of appetite

16 Posterior Pituitary – A Different BreedHormones are produced in neurons of hypothalamus Stored in axon terminals that extend into pituitary Release is stimulated with nerve impulses not chemical signals Rely on 2nd messengers A.K.A. Neurohypophysis ‘neural undergrowth’

17 Posterior Pituitary HormonesAntidiuretic Hormone (ADH) a.k.a. vasopressin Increases water retention at kidneys & arteriole vasoconstriction Hyposecretion  ‘diabetes insipidus’ (cause - head trauma) Symptoms include??? Hypothalamus – measures blood [solute] Alters kidney function – maintain water balance

18 Posterior Pituitary HormonesOxytocin Stimulates uterine contractions during labor Triggers milk ejection (“letdown” reflex) during nursing Synthetic form used to induce labor or stop postpartum bleeding

19 Thyroid & Parathyroid GlandsBelow larynx 2 Lobes & Isthmus Produces 2 hormone types Metabolic & [Ca2+] regulation 4-8 tiny glands - posterior aspect of the thyroid Produces 1 hormone [Ca2+] regulation

20 Thyroid Gland Follicles produce glycoprotein thyroglobulin(Thyroglobulin + iodine) fills follicles is precursor of thyroid hormone Parafollicular cells produce the hormone calcitonin

21 Thyroid Hormone (TH) TH = 2 Hormones Actually two related compoundsT4 (thyroxin); has 2 tyrosine molecules + 4 bound iodine atoms T3 (triiodothyronine); has 2 tyrosines + 3 bound iodine atoms

22 Thyroid Hormone (TH) Functions Increases metabolic rateRegulates tissue growth & development Especially nervous system Increases reactivity of mature nerve cells Heart rate, digestive motility Guess ‘who’ regulates it’s release??? Catecholamines – epinephrine, norepinephrine, dopamine etc.

23 Transport and Regulation of THNegative feedback regulation of TH release

24 Synthesis of Thyroid HormoneFollow the 7 Steps Iodide enters & converted to iodine &… binds with thyroglobulin (tyrosine + iodized thryoglobulin) enters lysosome thyroglobulin removed & T3 & T4 go to blood T3 10x more active than T4 - T4 converted to T3 by peripheral tissues enzymes

25 Homeostatic Imbalances of THHyposecretion in adults— endemic goiter if due to lack of iodine ; myxedema Hyposecretion in infants—cretinism Hypersecretion—Graves’ disease Myxedema = ‘mucous swelling’ – low BMR, chills, constipation, thick dry skin & puffy eyes, edema, lethargy & mental sluggishness Goiter = enlarged thyroid occurs if myxedema results from lack of iodine. Follicular cells produce colloid but cannot iodinate it and make functional hormones. Pituitary gland secretes increasing TSH, but only causes increase size of follicles as more colloid accumulates. Cretinism = Graves = autoimmune disease where production of antibodies that mimic TSH cause continuous release of TH. excessive thyroxin – high metabolic rate, exopthalamia, weight loss (autoimmune) insufficient thyroxin – small stature, mental retardation, low body T, fat buildup insufficient thyroxin – lethargy, low body T., swollen face, edema, leathery skin

26 Thyroid & Parathyroid Balancing Act- Osteoblast activity - Ca2+ uptake in bone FEEDBACK - Ca2+ absorption - Osteoclast activity - Ca2+ reabsorption

27 Homeostatic Imbalances of PTHHyperparathyroidism due to tumor Bones soften and deform Elevated Ca2+ depresses the nervous system and contributes to formation of kidney stones Hypoparathyroidism following gland trauma or removal Results in tetany, respiratory paralysis, and death

28 Another More Holistic View

29 Adrenal (Suprarenal) GlandsStructurally and functionally, they are 2 glands in 1 Adrenal medulla—nervous tissue; part of the sympathetic nervous system (NE, E) Adrenal cortex—glandular tissue that synthesize & secrete 3 corticosteroids from 3 layers

30 Mineralocorticoids – Outer CortexMineralcorticoids Important - Aldosterone Regulate ECF electrolytes esp. Na+ and K+ Na+  affects ECF volume, BV, BP, other [ions] K+  sets RMP of cells Aldosterone increases reabsorption of Na+, H2O retention, & secretion of K+

31 Glucocorticoids – Middle Cortex Cortisol & CortisoneGeneral Function Function to regulate carb. metabolism Released in response to ACTH, eating patterns, activity & stress Maintain BP by increasing vasoconstriction & suppress inflammation When someone experiences a stressful event, the level of glucocorticoids in their blood rises. Via specific receptors in the hippocampus, this activates the hypothalamus, which then secretes corticotropin-releasing hormone (CRH). The CRH in turn causes the pituitary gland to release adrenocorticotropic hormone (ACTH) into the bloodstream, from which it enters the adrenal glands and causes them to secrete cortisol. This process creates a negative feedback loop in which the excess cortisol activates the brain's glucocorticoid receptors and suppresses the production of CRH. In depressed patients, however, this loop no longer works, resulting in excess production of CRH and hence of cortisol. Many seriously depressed patients have high blood levels of cortisol, caused by chronic stress.

32 Glucocorticoids – Middle Cortex Cortisol & CortisoneHow it Works #1 metabolic effect is ‘gluconeogenesis’ protein  AA  glucose (in liver) Promotes rises in blood glucose, fatty acids, and amino acids Gluconeogenesis – synthesis of glucose from a noncarbohydrate precursor

33 Homeostatic Imbalances of GlucocorticoidsHypersecretion—Cushing’s syndrome Hyperglycemia Redistribution of body fat Easy bruising, poor wound healing Loss of body protein Tx – remove pituitary OR adrenals…why??? Cushing’s syndrome – glucocorticoid excess VS Cushing’s disease - caused by an ACTH-releasing pituitary tumor Suppresses inflammation, immune function & causes gluconeogenesis which harvests nutrients such as fat & protein breakdown products to produce more glucose

34 Homeostatic Imbalances of GlucocorticoidsHyposecretion—Addison’s disease Weight loss High K+, low Na+ Hypoglycemia Bronzing of the skin Fatal if untreated ACTH activates MSH receptors on melanocytes Usually involves both deficit of glucocorticoids & mineralcorticoids  which is why patients experience high K+ & low Na+ because of deficiency of aldosterone Leading to hypotension & dehydration due to inappropriate fluid & electrolyte balance Alpha MSH is identical to ACTH in the 1st 13 AA  due to this similarity it is thought that ACTH is able to stimulate melanocytes to produce melanin.

35 Gonadocorticoids (Sex Hormones) – Inner CortexPrimary function – supplement hormones released in ovaries & testes May contribute to The onset of puberty The appearance of secondary sex characteristics Sex drive Nothing to do with anything

36 Adrenal Medulla NS controlled  80% E & 20% NERemember ‘sympathomimetic’ 2 hormones exert ‘same’ effects E. metabolic activities, bronchial dilation, & BF to skeletal muscles & heart N peripheral vasoconstriction & BP, heart rate & stroke volume

37 Thymus 2 lobed organ – high in chest, anterior to aortaFetal development & 2 yrs post-birth  atrophy Produces thymosin (& others)  stimulate lymphocyte production Autoimmune diseases often associated with enlarged thymus

38 Pineal Gland Produces melatonin, derived from serotoninMelatonin may affect Timing of sexual maturation and puberty Day/night cycles Physiological processes that show rhythmic variations (body temperature, sleep, appetite) 3rd ventricle – part of epithalamus

39 Stress & Adaptation – Hans SelyePhysical or psychological – response varies Hypothalamus - monitors & can set homeostasis to new values Eustress VS Distress

40 Stress & Adaptation – Hans SelyeGeneral Adaptation Syndrome (GAS) Alarm Stage Resistance Stage Exhaustion Stage

41 Fight or Flight – Plateau – FailureAlarm - immediate Hypothalamus, symp. NS & adrenal medulla What is the reaction? HR BP vessels respiration RBC # glyc/gluc sweat digestion Resistance – long-term modification Hypothalamus  pituitary Angiotensin ACTH  glucocorticoids TSH  thyroxin GH ADH Inc. E. availability!!! Build Circulate i.e. Physical Fitness Exhaustion – loss of battle (possibly death) Continual K+ loss Glucocorticoid depletion Cell starvation Immune failure

42 Pancreas Exocrine cells  enzyme-rich digestive juices Endocrine cellsLong, flat organ behind the stomach Exocrine cells  enzyme-rich digestive juices Endocrine cells Alpha ()  Glucagon Beta ()  Insulin

43 Diabetes mellitus

44 Homeostatic Imbalances of InsulinDiabetes mellitus (DM) – I & II Alternative Table ‘Endocrine’ 16