Bio117 Chapter 7: Endocrine System

Hormones

Organic (not carbon dioxide)

Living Cells (not chemicals from dead cells)

Localized (not glucose needed in every cell)

Distance (not neurotransmitters)

Target Cells with Specific Receptors (not nutrients)

Exocrine Glands

Sweat glands, oil glands, tear ducts

Endocrine Glands

Hypothalamus, thyroid glands, pituitary gland, adrenal glands, pancreas

Endocrine System

collection of endocrine glands throughout the body that secrets hormones into the blood stream to alter the body’s physiology to help maintain homeostasis.

Parts of Endocrine System

Hypothalamus, anterior pituitary, thyroid, thymus, liver, adrenal medulla, adrenal cortex, kidneys, intestines, pineal (epiphysis), posterior pituitary, parathyroid glands, heart, stomach, pancreas, ovaries, uterus, placenta, testes

Eicosanoids

Unusual story, “local hormone”, derives from membrane phospholipids, can act on many levels: 2nd messengers, autocrine, paracrine, hormone

Growth Factors (GF)

Unusual story, can be hormones, cytokines, and paracrines, often influence cell cycle checkpoints

GF Examples

Epidermal GF, Ovarian GF, FDGF (Fibroblast-derived), IGF (insulin-like GF)

Oncogenes

cancer-linked genes, associated with GF-associated genes

Oncogene Products

include altered versions of: affected GF, GF receptor, and protein downstream (chain of communication)

APUD

Amine Precursor Uptake Decarboxylation

APUDomas

Unusual story, tumor of APUD cells, Ectopic secretion (secretion in the wrong location), secrete biogenic amines, protein or peptide hormones are often co-secreted with amines

APUDoma Example

Men can sometimes have tumors(APUDomas) in the lungs that produce hCG (Chronic Gonadotropin hormone normally produced in the placenta), they can test positive for pregnancy test

Amine Examples

Epinephrine, norepinephrine, histamine, serotonin, dopamine, melatonin

Steroid Structure

4 member ring structure (3 6-membered and 1 5-membered rings)

Vitamin D (Calcitriol)

Unusual story, Ex. Cod liner oil, vitamin acting like a hormone

Syntheisis of Vitamin D3 (Calcitriol) from Cholesterol

Need to remember:

25-Hydroxyvitamin D3 [25(OH)D3]

→1,25-Hihydroxyvitamin D3 [1,25(OH)D3]

(most potent version of vitamin D3)

• has hormonal effects on kidneys, intestinal tract, and bones

Chemicals of Renin-Angiotensin System

Unusual story,

• Renin (enzyme - protease)

• Angio - means artery or blood vessel

• Angiotensnogen (inactive precursor) → Angiotensin I (inactive 10 aa peptide) → Angiotensin II (active 8 aa peptide) - causes blood pressure to rise→ Angiotensin III (inactive 7 aa peptide)

Chemistry: Peptides, Polypeptides, and Proteins

• vary in size and sequence

• water soluble

• synthesized in rough ER as a “prohormone”

• Ex. Proopiomelanocorticotropic (POMC)

• Post-translationally cleaved and modified in smooth ER and Golgi

• Stored in secretory vesicles

Glycoproteins

proteins with carbohydrates attached to their surfaces

Modifications of Preprohormones

Preprohormone ————————-

Prohormone ——————

Hormone(s) —— ——

Hormone Families

• Similar genes result in similar hormones

• Oncogene hormones can bind to hormone receptors of same hormone family

• Hormone Family Ex.

  • Glycoprotein hormones (FSH, LH, TSH, hCG)

  • AVP and Oxytocin

  • Insulin, IGF-I, IGF-II, Relaxin

  • different MSH variants (Melanocyte Stimulating hormone

    • POMC can be clipped into three different MSH versions

Chemistry: Biogenic Amines

• Water soluble

• Modified amino acids: decarboxylated

• Synthesized in cytoplasm, stored in vesicles for secretion

• Ex.

  • Histamine from histidine (essential AA)

  • Serotonin from Tryptophan (essential AA)

  • Melatonin from Tryptophan (essential AA)

  • Catecholamines from tyrosine (nonessential AA)

    • Dopamine

    • Epinephrine

    • Norepinephrine

Chemistry: Steroids

• Hydrophobic

• Derived from Cholesterol (27C)

• NOT stored

• Not hormone families b/c not gene encoded

Breakdown of Cholesterol into Different Steroids

Cholesterol (27C) →

Progestines (21C, progesterone (pregnancy hormones)) →

Corticoids (21C, mineralcorticoids, glucocorticoids) OR Androgens (19C) →

Estrogen (18C)

Cannot go back up the chain

Chemistry: Iodinated Amino Acids

• Made of one amino acid each

• made only in thyroid gland

• Hydrophobic

• AA = Thyronine (derived from tyrosine)

  • Acts as a lipid, not one of the 20 regular amino acids

• Complicated synthesis: precursor is stored, but finished hormone is not (formed when needed)

  • Tetraiodothyronine (T4) = Thyroxine

  • Triiodothyronine (T3)

Chemistry: Eicosanoids

• Derived from fatty acids w/ 20 carbons

• Hydrophobic

• Not stored (synthesized when needed)

  • Prostaglandins

  • Prostacyclins

  • Thromboxanes

  • Leukotrienes

  • HETEs

Mechanism of Action: Hydrophilic Hormones

• Can’t cross cell membranes

• Use of transmembrane receptors coupled with second messenger system

• Alters preexisting enzyme activities

• Relatively rapid, brief effects

Mechanism of Action: Hydrophobic Hormones

• cross membranes freely

• intracellular receptors coupled to altered gene expression

  • Steroids use cytosolic and nuclear receptors

  • Thyroid hormones use nuclear and mitochondrial receptors

• Slow, long lasting effects

Different Inhalers for Asthma

• Rescue Inhaler - contains epinephrine (fast acting)

• Maintenance Inhaler - contains steroids (slow, long-lasting)

Hormone Effectiveness

Determined by:

• Amount of hormone secreted

• Delivery rate via blood stream

• Potency at target cells

• Rate of clearance

Common Hormones that are Lacking from the Body

• Testosterone

• Estrogen

• Thyroid Hormones

• Insulin (Diabetes)

Mechanisms of Hormone Regulation

• Endogenous rhythms (cyclic, different rates at different times)

• Neural

• Hormonal

• Substrate

• Feedback Regulation

  • Short

  • Long

Substrate Regulation

Pairs:

• insulin, glucagon - glucose

• parathyroid hormone, calcitonin - Ca++

• aldosterone, atrial natriuretic hormone - Na+/K+

Types of Calcemia

hypercalcemia, eucalcemia, hypocalcemia

Hormone Circulation in Blood

• Hormone solubility affects hormone concentration in blood

• Hydrophobic hormones and some smaller hydrophilic hormones tend to have binding/transport proteins in plasma

• Most binding proteins synthesized in liver

Nonspecific Binding Proteins

• Ex. Albumins (blood plasma protein, regulates osmolarity) - most abundant in body

• Sticky trait

  • low affinity

  • low specificity

  • high capacity b/c high abundance

Specific Binding Proteins

• S3X hormone binding globulin

• Thyroid hormone binding globulin

• Androgen binding protein

Hormone Binding Protein Effects

• Increase total plasma hormone concentration

• Increases half-life of hormones in circulation

• homogenizes the dosing from tissue to tissue

  • hormones → heart → lungs → heart → rest of the body

• 95-99% hormones bound to proteins in blood

Step-Up Reactions

• alters hormone structure to increase potency

• Ex. T4 → T3 (stronger)

• Ex. T (testosterone) → DHT (dihydrotestosterone)

Step-Down Reaction

• alters hormone structure to decrease potency

  • weaker hormones are used to prevent overdosing

• Ex. T → E2 (estradiol)

• Ex. T3 → T2 (has only 2 iodines)

• Ex. T4 → rT3 (revers T3)

Changes in Potency of Target Cells

• Up-Regulation (rapid, via exocytosis)

• Down-Regulation (rapid, via endocytosis)

• Desensitization of target cells following prolonged over exposure

Co-Exposure to Agonists

• Additive effects: competitive agonists

• Synergism: noncompetitive agonists (can be before or after hormone)

• Permissive effects: noncompetitive agonists (needs to be first before hormone to have an effect)

  • Ex. Thyroid and Epinephrine

Fate of a Hormone

• Some reach target cells (can be released back to blood stream afterwards)

• metabolized by liver, kidneys, or while in blood

• excreted in urine/feces

Enzymes for Amines

• MAO (Monoamine oxidase) enzymes - various products

Enzymes for Steroids

• HSDH (not specific, low specificity) enzymes - altered steroids

• reductases - altered steroids

• sulfotransferases - steroid sulfates

• glucuronidases - steroid glucuronides

Enzymes for Thyroid Hormones

• Deiodinases (takes of iodines) - Reverse T3, T2, others

Hypothalamus and Posterior Pituitary Gland Pair

• Secretes 2 peptides (both a.a.)

  • Oxytocin (OXY or OT)

    • stimulates milk-let down by mammary glands

    • childbirth labor contractions of uterus

    • Controlled by neuroendocrine reflexes from nipples and uterus

  • Vasopressin (AVP) - ADH (Antidiuretic hormone)

    • Vaso - blood vessel

    • Pressin - pressure

    • Stimulates vasoconstriction and fluid retention to increase blood pressure

    • Controlled by low blood pressure (baroreceptors) and hypertonicity (osmoreceptors)

Urination Effects on Blood Pressure

• Urinating makes body lose salt or water causes blood pressure to drop b/c blood volume drops

Neuroendocrine Reflex

stimulus → neuro signal → hormonal signal

Hypothalamus and Median Eminence Pair

• Axons travel through median eminence

• Secretes several hypophysiotropic hormones, releasing hormones (RH), and release-inhibiting hormones (RIH)

  • Thyrotropin RH

  • Corticotropin RH (CRH)

  • Growth hormone RH (GHRH)

  • Somatostatin (SS = GHRIH)

  • Dopamine (DA)

    • amine, not peptide

  • Gonadotropin (GnRH)

Median Eminence Pathway

Median Eminence → A.P. → peripheral endo organ →

→ = hormone release

Anterior Pituitary (AP)

• Secretes

  • Thyroid Stimulus Hormone (TSH)

  • Follicle Stimulus Hormone (FSH)

    • stimulates gonad

  • Luteinizing Hormone (LH)

    • stimulates gonad

  • Adrenocorticotropic hormone (ACTH)

    • stimulates adrenal cortex

  • Growth Hormone (GH)

  • Prolactin (Prl)

  • Beta-Endorphin

  • Beta-Lipotropin (LPH)

  • MSH

Can ACTH be cleaved into Alpha-MSH?

No

FSH promotes?

Gametegenesis (production of sperm and eggs)

LH promotes

Steroidgenesis (steroids and estrogen)

Prolactin

• affects mammary glands (milk production)

• release of dopamine to inhibit prolactin release

Anatomy of Thyroid Gland

• organized into hollow thyroid follicles

  • each w/ wall of follicular cells

  • lumen (made of extracellular material called colloid) inside follicles

  • parafollicular cells (C cells) - between follicles in connective tissue

  • C cells secrete calcitonin

  • secretion of thyroglobulin

Thyroid Hormones

• Iodinated amino acids

  • made only in thyroid gland

  • hydrophobic

  • AA = Thyronine, derived from tyrosine

  • complicated synthesis

    • precursor is stored, actual hormone is not (formed as needed)

      • Tetraiodothyronine (T4) = Thyroxine

      • Triiodothyronine (T3)

Synthesis of Thyroid Hormones

Nucleus → Rought ER → Thyroglobulin secretion → (exocytosis) thyroglobulin

Thyroglobulin + I^- (comes in through Na/I Symporter) → Iodination → Conjugation into T3 or T4 → Proteolysis

Functions of Thyroid Hormones

• Maintains normalcy

• important functions in fetal and newborn development

  • regulates development of central nervous system around time of birth

  • Low thyroid hormone levels lead to mental retardation (cretinism)

• Targets in adult:

  • Skeletal muscle tissue

  • Liver Heart

Effects of Thyroid Hormone (TH) in Adults

• Metabolic rate

• Intermediary metabolism

• Mood

• Growth

Hypothyroidism

• Typical adult symptoms:

  • Mood, weight gain, cold, lethargic/dull

• Common causes

  • Iodine deficiency

  • Hashimoto’s thyroiditis

• Common side effect: Goiter

Hyperthyroidism

• Typical symptoms:

  • Mood, weight loss, hot, sweaty, irritable

• Common causes

  • Grave disease

• Common side effect:

  • Exophthalmos - bulging eyes

  • Goiter

Endocrine Disorders: Hyperactivity

• X-S hormone secretion or target hypersensitivity

  • Gigantism - excess GH (growth hormone) in a child

  • Acromegaly - Excess GH in an adult

Endocrine Disorders: Hypoactivity

• Insufficient hormone secretion or target cell insenstivity

  • Dwarfism - insufficient GH in a child

  • Diabetes mellitus (sugar diabetes) - condition of having high blood sugar levels due to insulin insufficiency

    • Type I diabetes mellitus: caused by lack of insulin

    • Type II diabetes mellitus: caused by a desensitization of peripheral target cells to insulin

Endocrine Disorders: Inappropriate Activity

• Unregulated secretion from the wrong source and/or at the wrong time

  • APUDomas associated with ectopic hormone secretion, causing:

    • Acromegaly (ectopic GH)

    • Cushing’s Syndrome (ectopic ACTH)

H-P-T Axis

Hypothalamus —TRH (Thyrotropin Releasing Hormone)→ Anterior Pituitary (Adenohypophysis) —TSH (Thyroid Stimulating Hormone)→ Thyroid Gland —TH (Thyroid Hormone) - T4, T3→ Target

H-P-AC Axis

Hypothalamus —CRH (Corticotropin Releasing Hormone)→ Anterior Pituitary (Adenohypophysis) —ACTH (Adrenocorticotropic hormone)→ Adrenal Cortex —Cortisol→ Target

H-P-G Axis

Hypothalamus —GnRH (Gonadotropin Releasing Hormone)→ Anterior Pituitary (Adenohypophysis) —LH/FSH (Luteinizing hormone/Follicle-stimulating hormone)→ Gonads —Estrogens/Androgens→ Target

H-P-AC Axis

Hypothalamus —GHRH (Growth Hormone Releasing Hormone)→ Anterior Pituitary (Adenohypophysis) —GH (Growth hormone)→ Adrenal Cortex —IGF-1 (Insulin-like growth factor 1)→ Target

TRH

thyrotropin-releasing hormone

TSH

thyroid-stumulating hormone

TH

thyroid hormone

CRH

corticotropin-releasing hormone

ACTH

adrenocorticotropic hormone

COR/CORT

cortisol

GnRH

gonadotropin-releasing hormone

LH

luteinizing hormone

FSH

follicle-stimulating hormone

GHRH

growth hormone-releasing hormone

GH

growth hormone

IGF-1

insulin-like grow-th factor 1

T4

tetraiodothyronine OR thyroxine

T3

Triiodothyronine

C Cells

parafollicular cells

DA

• dopamine

• inhibits prolactin

SS

• somatostatin

• inhibits growth factors

MSH

melanocyte-stimulating hormone

Prl

• Prolactin

• promotes breast development and milk production

LPH

beta-liptropin

beta-END

beta-endorphin

AVP

vasopressin (9 a.a.), ADH

ADH

antidiuretic hormone

OXY/OT

oxytocin (9 a.a.)

Neurohypophysis

posterior pituitary

Adenohypophysis

anterior pituitary

Hypothalamo Hypophyseal Portal Vessel

a specialized network of blood vessels that directly connects the hypothalamus to the anterior pituitary gland

Where are most hormones degraded?

liver and kidney, less common places are in blood and target cells

Degraded Proteins

broken down into amino acids and reused