Cell Communication and Signaling

• Cells communicate via electrical or chemical signals
• Electrical signals are changes in potential membrane
• Chemical signals secreted into the extracellular fluid

Cell Communication Types

• Gap junctions facilitate direct cytoplasmic connections between cells
  • Transfer electrical and chemical signals like ions, small molecules, amino acids, ATP, and cAMP
• Contact-dependent signals use cell adhesion molecules (CAMs)
• Paracrine signals are locally acting chemicals affecting different cell types
• Autocrine signals exert effects on same cells that secrete them
• Long-distance communication is regulated by nervous and endocrine systems
  • The Nervous system fires action potentials to release neurotransmitters
  • The Endocrine system secretes hormones

Glands

• Endocrine glands produce hormones into bloodstream without ducts
  • Examples include pituitary, thyroid, parathyroid, adrenal, and pineal glands
• Exocrine glands secrete nonhormonal substances (sweat, saliva) with ducts to membrane surfaces
  • Examples include simple tubular intestinal glands and simple branched alveolar sebaceous glands
• Neuroendocrine glands include the hypothalamus
• Some organs have both exocrine and endocrine functions, such as the pancreas, gonads, and placenta
• Scattered endocrine tissues are found in adipose cells, the thymus, and walls of organs like the small intestine, stomach, kidneys, and heart

Endocrine vs Nervous System

• Both the nervous and endocrine system regulate distance communication among body cells
• The nervous system triggers action potentials to release neurotransmitters
• The endocrine system secretes hormones, which are produced by hormone-producing cells and glands
  • Functions include reproduction, growth, development, electrolyte/water/nutrient balance, cellular metabolism regulation, and body defense mobilization

Hormones

• Hormones are chemical messengers secreted into bloodstream that trigger responses in distant organs
  • They exert effects at low concentrations from 10-9 M to 10-12 M

Hormone action on target cells

• Alters plasma membrane permeability and/or potential by opening or closing ion channels
• Stimulates synthesis of enzymes or other proteins
• Activates or deactivates enzymes
• Induces secretory activity
• Stimulates mitosis

Aminoacidic vs Steroid Hormones

• Amino acid-based hormones are derived from amino acids like tyrosine and tryptophan and made in many tissues
  • For example, epinephrine and norepinephrine
• Steroid hormones are synthesized from cholesterol and made in specific organs such as the gonads and adrenal cortex
  • For example, testosterone and estradiol

Water vs Lipid Soluble Hormones

• Water-soluble hormones include amino acidic and protein hormones (excluding thyroid hormones)
  • They mix freely with water, are transported easily in the blood, and cannot pass through the plasma membrane
  • They act on cAMP and PIP2-calcium signaling mechanisms
    • Calcium ions act as second messengers to trigger responses like smooth muscle contraction
• Lipid-soluble hormones include steroid and thyroid hormones
  • They do not mix freely with water, must bind to transport proteins in the blood, and can pass through the plasma membrane

Target Cells

• Target cells need receptors for a specific hormone, and target cell specificity is a factor
  • Target cells have specific receptors such as ACTH receptors only on adrenal cortex cells
  • Target cell activation depends on hormone blood levels, the number of receptors on target cells, and binding affinity between receptor and hormone
  • Up-regulation means target cells form more receptors to low hormone levels
  • Down-regulation means target cells lose receptors in response to high hormone levels

cAMP

• Water-soluble hormones use cAMP signaling mechanism
  • A hormone (first messenger) binds to receptor, activating G protein
  • G protein activates adenylate cyclase, which converts ATP to cAMP (second messenger)
  • cAMP activates protein kinases that phosphorylate proteins
  • Activated kinases phosphorylate proteins, activating or inactivating them
  • cAMP is rapidly degraded by enzyme phosphodiesterase
  • Intracellular enzymatic cascades have amplification effects where one ligand is amplified into many intracellular molecules

Lipid Soluble Hormone Action

1. Diffuses into target cells and bind with intracellular receptors
2. Enters the nucleus and binds to specific DNA regions
3. Prompts DNA transcription to produce mRNA
4. mRNA directs protein synthesis
5. Promotes metabolism and structural protein synthesis

Endocrine Gland Stimuli

• Humoral stimuli are changes in blood levels of ions and nutrients
  • Declining blood calcium stimulates the parathyroid glands to secrete PTH, which causes calcium concentration to rise
• Neural stimuli includes nerve fibers stimulating hormone release
  • Sympathetic nervous system fibers stimulate the adrenal medulla to secrete catecholamines
• Hormonal stimuli include hormones stimulate other endocrine organs to release their hormones

Feedback

• Hormone secretion is modulated by feedback mechanisms like negative feedback

Hormone Circulation

• Lipid-soluble hormones are all steroid hormones and thyroid hormone
  • The adrenal cortex, gonads, and thyroid gland are sources
  • They are NOT stored in vesicles, but it is bound to plasma proteins
  • Long half-life and intracellular receptors, activating genes for protein synthesis
• Water-soluble hormones are amino acid-based hormones except thyroid hormone
  • Sources are other endocrine glands
  • Stores in vesicles and freely circulates
  • It has a short half life with cell membrane receptors and second-messenger systems

Metabolites

• The kidneys and liver have degrading enzymes that turn active hormones into inactive metabilites
• These metabolites are excreted in the urine or bile
• For example, permissiveness is when one hormone can't exert its effects without another hormone being present, and synergism is when multiple hormones produce the same effects
• Antagonism is when one or more hormones oppose the action of another hormone

Review of A&P

• Review functions of the hypothalamus and list functions of the hypothalamic neurohormones oxytocin and ADH

Hypothalamus and Hormones

• The hypothalamus produces releasing and inhibiting factors, including TRH, CRH, GnRH, GHRH, GHIH, and PIH
• Oxytocin stimulates uterine contraction and is released during childbirth
  • It triggers milk ejection and surges during arousal and orgasm
  • Also important in satisfaction and bonding
• ADH prevents urine formation and regulates water balance
  • It targets kidney tubules to reabsorb water and is triggered by pain, low blood pressure, drugs, and high solute concentration
  • High concentrations lead to vasoconstriction
  • Known as vasopressin
• The hypophyseal portal system connects the hypothalamus to the anterior pituitary
  • A vascular connection made up of two capillary plexuses connected by veins
  • It carries releasing and inhibiting hormones to anterior pituitary to regulate hormone secretion

Effects of GH

• Growth hormone (GH) mediates growth through insulin-like growth factors (IGFs)
• It stimulates nutrient uptake and collagen formation for bone matrix
• Direct actions include fat and carbohydrate metabolism
• Hypersecretion of Growth Hormone
  • Gigantism in children
  • Acromegaly in adults
    • Thickening of face and hands
• Hyposecretion of Growth Hormone
  • Pituitary dwarfism in children

Thyroid

• The thyroid gland produces thyroid hormones
  • T4 (thyroxine) contains 2 tyrosine molecules + 4 bound iodine atoms
  • T3 (triiodothyronine) contains 2 tyrosine + 3 bound iodine atoms
  • T3 is more active and powerful, but T4 is more concentrated in the blood
  • Affects all cells in the body and regulates metabolic rates, heat production, and tissue growth
  • Skeletal and nervous system development + Maintenance of blood pressure
  • Regulation of TH release by negative feedback
  • TH is storied extra cellularly and iodine attaches to tyrosine, which are later cleaved into T3 and T4

Thyroid Imbalances

• Myxedema is the Hyposecretion of TH in adults and causes bags under the eyes
• Goiter: enlarged glands and can arise from lack of iodine
• Cretinism is hyposecretion in infants
• Grave's disease is hypersecretion and can be meddicated with medication

Calcitonin

• Produced by parafollicular (C) cells
  • Inhibits osteoclast activity and release calcium uptake
  • Stimulates calcium uptake

Parathyroid Gland

• 4-8 tiny glands embedded in posterior of thyroid

PTH

• Parathyroid cells secrete PTH for calcium homeostasis
  • PTH stimulates osteoclasts, enhances calcium reabsorption and secretion of phosphate by kidneys, and activates vitamin D
• Negative feedback control is when rising calcium in blood inhibits PTH release
• Hyperparathyroidism, caused by a tumor, results in soft bones and high calcium levels
• Hypoparathyroidism, from trauma or magnesium deficiency, results in muscle spasms, respiratory paralysis, and death

Adrenal Gland

• Pyramid-shaped organs atop kidneys
• The Adrenal medulla synthesizes epinephrine (80%) and norepinephrine (20%) in brief responses
  • Results in vasoconstriction, increased heart rate and blood glucose, blood diverted for brain activity
• The Adrenal Cortex releases mineralocorticoids
  • Regulates electrolytes and aldosterone
• Functions of the Adrenal Gland
• Aldosterone is a mineralcorticoid that stimulates Na+ reabsorption and water retention
• Cortisol is released in response to ACTH, patterns of eating and activity, and stress. It also "save glucose"

Hormones

• Adrenal cortex synthesizes corticosteroids from three layers of glandular tissue
  • Zona glomerulosa makes mineralocorticoids to regulate Na+ and K+
  • Zona fasciculata makes glucocorticoids to keep blood glucose levels constant
    • Maintaining blood pressure and for vasoconstriction
  • Zona reticularis makes sex hormones

Adrogens

• Male sex hormones
• Androgens get converted into testerone
• It can contribute to puberty and Sex drive in women
• Hypersecretion triggers adrenogenital syndrome

Adrenal Gland Issues

• HypOsecretion presents as Addison's disease
  • In mineralocorticoids: Low Glucosae
  • Hyperpigmentation via increased melanin
• HypERsecretion presents as Cushing's syndrome
  • Cartilage damage and inflammation with "moon" face"

Aldosterone Control

• Controlled by decrease of blood pressure and rising K+ levels
  • Increased K influences zona
  • ACTH may cause increase levels
• Homeostatic IMBALANCES lead to the increase of edema and hypertension

Pancreas

• Endocrine and Exocrine -Alpha make glucagon while Beta is insulin

Insulin And Glucogen

• Glucogeneolysis can cause glyogen to breakdown in the pancrease when its needed
• Insulin promotes cells to uptake glyogen and uptake amino acids and fat metabolism
• Rising amino acids release insulin
• Insulin is released when parasympatethic nerves are activated

Diabetes

• Insulin may be hyper or hypo active
• The person may feel nauseous if high

Ketones

• Fats are used instead of fuels which causes the sugar levels to rise
• The body can go in hyper activity and cause O2 disruptations

Diabetes Sign

• Three cardinal signs of DM:
  • Polyuria, Polydypsia and Polyphagia
  • "Stress, Portrait of a Killer" - This shows data leading deterious health