CC 3 - Endocrinology Up to Thyroid Function Tests

ENDOCRINOLOGY HORMONE   

the chemical messengers produced by the endocrine cells that travel through the circulation to specific body cells body cells contain receptors for specific hormones called TARGET CELLS only those cells containing receptors will bind hormones –very specific, conc’n dependent & reversible

CLASSIFICATION OF HORMONES A. PROTEIN HORMONES  composed of AA (peptides, chains of 8 AA or less, amines)  synthesized in the endocrine glands as a larger precursor molecules called PREPROHORMONES –contains a leader sequence of AA called SIGNAL SEQUENCE –cleaved from the molecules called PROHORMONES –enzymatically cleaved to smaller molecules –active hormones –packaged into secretory vesicles  does not attach to plasma CHONS & circulates in the blood as free hormone  short half life B.   

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STEROID HORMONES synthesized in the cytoplasm by multienzyme processes derived from CHOLESTEROL separated into groups based on the no. of carbon presents:  C 18 – estrogens  C 19 – androgens  C 21 – gluococorticoids, mineralocorticoids & progesterone freely diffuse across the plasma mem. & into the bloodstream bind to specific plasma CHON w/c allows them to remain in circulation for longer than the unbound or free form of the hormone take longer to initiate their action & once started, the action is sustained for a prolonged period longer half life –bec. of their binding to the plasma CHON carriers

GROWTH HORMONE (GH)   

composed of AA & share many of the same charac. as the CHON hormones from indiv. cells or group of cells has its own specific extracellular receptor since they cannot cross the plasma mem.

NEUROTRANSMITTERS (NT) 

epinephrine/norepinephrine –may serve as either a hormone or NT, the diff. is the site of synthesis & action

REGULATION OF HORMONE SECRETION A. NEGATIVE FEEDBACK  the final hormone produced regulates its own secretion by inhibiting the secretion of 1 or more of the precursor hormones TRH (Thyroid Releasing H) – by hypothalamus ↓ TSH (T Stimulating H) – by pituitary gland ↓ TH – by thyroid gland B.   

POSTIVE FEEDBACK the final hormone produced actually enhances or induces the initial hormone & causes its own prodxn to be ↑ rare; final hormone enhances or induces initial hormone  ↑ production Oxytocin

MECHANISM OF ACTION A. PROTEIN HORMONE ACTION  bind to extracellular receptors  activates an intracellular CHON (G) to transducer the signal to an enzyme (adenyl cyclase) to produce 2 nd messenger cAMP  2nd messenger will cause intracellular changes 

B. 

Bind to EC receptors  Hormone-receptor complex Activate IC protein (G)  transduce signal to Adenyl cyclase (enzyme)  produce 2nd messenger cAMP  cause IC changes

STEROID HORMONES ACTION diffuse across the plasma mem. to bind w/ their intracellular receptors

 a heat shock CHON dissociates from the receptor after binding  hormone-receptor complex migrates into the nucleus & binds w/ a specific region on the DNA  mRNA is produced & a CHON is synthesized DISORDERS OF THE ENDOCRINE SYS.  1.

2 categories: 1° DISORDERS  problem w/ the gland that produces the hormone (hyper/hyposecretion), the outside stimulating agents is N Hyper more difficult to correct than hypo Hypo – not detected until 80-90% of gland is nonfunctional

2.    

2° DISORDERS the gland that produces the hormone is capable of N fxn, the outside stimulating agents are either in excess or deficient hypersecretion of a hormone is often more difficult to correct than hyposecretion hyposecretion is often not detected until approx. 80%-90% of the gland is nonfunctional normal gland function, outside stimulating agents in excess or deficient

HYPOTHALAMUS -

part of brain; under 3rd ventricle & directly above pituitary gland secrete neuropeptides (hormones): inhibit/ stimulate hormones of Anterior Pituitary Gland (APG); regulatory hormones neurosecretory cells secrete the neuropeptides

Hypothalamic Hormones: Corticotropin Releasing Hormone (CRH)

↑ACTH, ß-lipotropin, ß-endorphin

Thyrotropin Releasing Hormone (TRH)

↑TSH

Gonadotropin Releasing Hormone (GnRH)

↑FSH, LH

Prolactin Inhibiting Factor (PIF=dopamine)

↓ prolactin (PRL)

Prolactin Releasing Factor (PRF/TRH)

↑ PRL

Growth HRH (GRH) / Somatocrinin

↑ GH

Growth HIH (GIH) / Somatostatin (SS)

↓ GH

Melanocyte Inhibiting Factor(MIF)

↓ Melanocyte-Stimulating H

ADH/ Arginine Vasopressin (AVP)

↑ reabsorption of H2O from glomerular filtrate & urine; Vasoconstriction of Smooth Muscles

Oxytocin

stimulate uterine muscle contraction; cause contraction of the breast muscles for the ejection of milk

 Pineal gland on the posterior wall of the 3rd ventricle of the cerebrum small “pine-cone” shaped structure exact fxn unknown; but synthesizes MELATONIN (synthesized from serotonin; can inhibit gonadotropic hormone in lower vertebrates {may or may not in humans}) “3rd eye”: regulates the circadian rhythm/ diurnal pattern ↑ production in dim light - sleepy, tired, depressed during nighttime Bright light inhibits melatonin – active, awake during daytime

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 Pituitary Gland (Hypophysis) -

connected to the hypothalamus by infundibulum or pituitary stalk through w/c the neuropeptides migrate to pit. gland contained in a depression of sphenoid bone: SELLA TURCICA; adjacent to chiasm of optic nerve “Master Gland” - secretes numerous hormones w/c triggers other glands to produce hormones enlargement leads to loss of vision 2 main lobes: a. Posterior Pituitary/ Neurohypophysis – smaller hypothalamic lobe; storage of Oxytocin (targets the breast and the uterus) & ADH/AVP (target organ is the kidney); synthesized in Hypothalamus; neuroectodermal in origin b. Anterior Pituitary/ Adenohypophysis –specialized secretory epith. cells: synthesize & stimulate numerous hormones  stimulates the secretion of other hormones except GH & PRL regulate their own secretion by a (-) Feedback to Hypothalamus  “short loop (-) feedback” TSH, ACTH, LH,FSH, except PRL & GH - others can stimulate other adrenal glands to produce H. TSH (thyroid stimulating hormone) – T3(triiodothyronin) and T4 (thyroxin) ACTH (adenocorticotrophic hormone)- target organ is the adrenal cortex; end hormone produced is cortisol LH and FSH – target organs are the gonads (testes for males; ovaries for females); testosterone is produced in males, estrogen and progesterone for females Growth factor- stimulates tissues such as cartilage, bones, muscles but these do not produce hormones Prolactin – target organ is the breast; increase the size of the breast to prepare it to produce milk  Secretory Cells of AP (staining property with H&E) 1. Acidophils - stains red; Somatotrophs (secrete GH) & lactotrophs/ mammotrophs (secrete PRL) 2. Basophils – stains blue; thyrotrophs (secrete TSH) and Gonadotrophs (secrete FSH and LH) 3. Chromophobe Cells – don’t stain; corticotrophs (secrete ACTH) Pituitary hormones (based on chemical configuration): 1. Polypeptides – hormones with intramolecular disulfide bonds (GH & PRL) 2. Glycoproteins –TSH, FSH, LH; share common α-subunit, differ in ß-subunit; ex: human chorionic gonadotrophin (hCG) 3. Single-chain peptides –hormones w/o disulfide bonds (ACTH) POSTERIOR PITUITARY HORMONES - ADH & Oxytocin – nonapeptides: contain 9 amino acids - both are inhibited by alcohol

1. ADH or Arginine Vasopressin (AVP) a. Maintain body’s H2O balance by promoting ↑ H2O reabsorption in the tubules of the nephrons of kidneys  less H2O in the urine (concentrating effect); ↑osmolality in urine compared to plasma b. Vasoconstriction of BV  “vasopressin”: maintain BP in traumatic injuries Administration of ADH can help prevent von Willebrand’s disease because ADH can release the von Willebrand factor 1º stimulus: ↑ plasma osmolality (↑ Na) detected by the osmoreceptors in the Hypothalamus RR of Plasma osmolality = 275-295 mOsm/Kg (>295  secretion of ADH)  ADH stimulation a. b. c. d. e.

ADH (binds) to V2 receptor (vasopressin) in distal convoluted tubules & collecting ducts  activates Adenyl Cyclase that will cause generation of cAMP (cyclic adenosine monophosphate); (serves as the 2nd messenger: responsible for intracellular changes) initiates phosphorylation of membrane CHON which causes ↑ in membrane permeability to H2O

 Symptoms of ADH Deficiency & Diabetes Insipidus: 1)

Polydipsia (↑ thirst)

2)

Polyuria (↑ urine output; typically >3L /24 hrs) *N=2L

 Laboratory Analysis A. -

RIA— Spec: plasma anticoagulated w/ EDTA in prechilled tubes centrifuge blood ASAP & remove plasma from cells plasma frozen until used for analysis ADH levels deteriorate with prolonged storage NV (healthy adult)= 2.3 – 3.1 picogm/mL or nanogram/L of plasma plasma ADH conc. report w/ Px plasma osmolality for EVERY test

Reference Ranges for ADH: Osmolality (mOSm/kg)

ADH (pg/mL) 270-280 280-285 285-290 290-295 295-300

300 mOsm/Kg  dehydrated) d. After 8hrs allow Px to drink (no more than twice urine vol. obtained in test to avoid acute hyponatremia).  Patient should be closely observed while test is being performed.  Normal: Should not have weight losses >3% & Serum/plasma osmolality w/in RR; urine osmolality must not go beyond 800 mOsm/kg of water  ADH deficiency: ↑ serum/plasma osmolality & ↓ urine osmolality over time tested (concentrating effect on plasma and diluting effect on urine) inversely prop: Plasma & urine osmolality alcohol: inhibit ADH & oxytocin cold temp: inhibit ADH

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2. Oxytocin (OT) most active in pregnant women At term  stimulates contraction of smooth muscles in the wall of the uterus (induce labor) Synthetic oxytocin can be used to induce labor induces lactation by stimulating contraction of the myoepethielial cells in the mammary glands (ejection of milk) premature labor  prevented by injecting alcohol intravenously Nonpregnant women and men have basal levels of OT – its role not been determined  2 Strongest Stimuli for Oxytocin release: a. Distention of the uterus b. Neonatal suckling of the nipple  Lab Analysis A. -

RIA – Plasma anticoagulated w/ EDTA in prechilled tube plasma can be frozen until used for analysis Reference Range = 1-5 pg/mL sample

ANTERIOR PITUITARY HORMONES: 1. Prolactin (PRL) by lactotroph (mammotroph) cells in the anterior pituitary gland helps stimulate dev’t. of breast tissue needed for lactation postpartum women: it induces synthesis of milk in the mammary gland  PRL Values a. -

Nonlactating women, men & children= < 20ng/mL actual function not fully understood Hypersecretion is associated with Hypogonadism (impaired gonads, incomplete fxn) in both men and women

b. 1st Trimester =