Last Lecture

• Endocrine System

  • Works in conjunction with nervous system
  • Hormones regulate metabolic activities of other cells, control reproduction, growth/development, homeostatic balances, cellular metabolism, body defenses
• Endocrine glands

  • Pituitary, thyroid, parathyroid, adrenal, and pineal glands
  • Neuroendocrine organ
  • Hypothalamus
  • Organs with exocrine and endocrine functions (pancreas, gonads, placenta)
  • Other tissues and organs that produce hormones (adipose cells, thymus, cells in walls of small intestine, stomach, kidneys, and heart)
• Hormone Chemical Structure

  • Amino acid-based hormones (water soluble except thyroid hormone)
  • Steroids (lipid soluble)
• Target cells

  Cells that have receptors for a specific hormone
• Action of Hormones

  1. Alter membrane permeability

  2. Stimulate synthesis of enzymes

  3. Activate or deactivate enzymes

  4. Induce secretory activity

  5. Stimulate mitosis
• Water-soluble hormone action

  1. Act on receptors on the plasma membrane - which are coupled to G protein 2nd messenger systems

  2. Cyclic AMP

  3. PIP2-calcium
• Lipid-soluble hormone action

  Act on receptors inside the cell
• Second Messenger cAMP

  1. G-protein linked 2nd messenger systems

  2. Cyclic AMP system

  3. Amplification occurs at these 2 steps, so the binding of a single hormone molecule can have a dramatic effect
• Second-Messenger Systems

  1. A water-soluble hormone molecule binds to a transmembrane protein acting as a receptor

  2. The receptor changes shape on the other side of the membrane, inside the cell

  3. The intracellular part of the receptor binds to an inactive G protein

  4. The G protein gives up a GDP, replacing it with a GTP

  5. The G protein is now activated and moves along the interior surface of the membrane

  6. The G protein binds to adenylate cyclase, activating the enzyme

  7. Adenylate cyclase converts multiple ATP molecules to cyclic AMP (cAMP)

  8. cAMP moves into the cytoplasm

  9. cAMP activates protein kinases

  10. Protein kinases phosphorylate other proteins & enzymes in the cytoplasm
• Cyclic AMP system


  Amplification occurs at these 2 steps, so the binding of a single hormone molecule can have a dramatic effect
• Other 2nd messengers

  • cGMP
  • PIP2-calcium signaling mechanism
• Intracellular Receptors and Direct Gene Activation

  1. Lipid-soluble hormones (steroids and thyroid) diffuse right across membrane

  2. Form a receptor-hormone complex

  3. Enter nucleus

  4. Turn on a gene
• Hormone blood levels

  Mostly controlled by negative feedback systems
• Hormone release triggers

  • Humoral stimuli
  • Hormonal stimuli
  • Neural stimuli
• Nervous system

  • Can also modify factors that turn on and turn off secretion
  • Blood glucose is allowed to rise beyond the normal range when sympathetic nervous system is engaged
  • Makes sure cells have resources needed
• Target Cell Specificity


  • Target cells must have specific receptors
  • Target cell activation depends on blood levels of hormone, relative number of receptors on/in target cell, and affinity (strength) of binding between receptor and hormone
  • Blood levels of a hormone can directly affect number of receptors on target cells
  • Up-regulation
  • Down-regulation
• Hormone Circulation in Blood

  • Bound - lipid soluble; attached to carrier proteins
  • Free - H2O-soluble hormones
• Blood Levels of Hormones

  • Affected by rate of release and how fast it's inactivated/removed from body
  • Some enzymatically degraded
  • Most removed by kidneys/liver
• Half-life

  • Time for level of hormone in blood to decrease by half
  • Varies by hormone
  • Water-soluble hormones have shortest half-lives
• Onset and Duration of Hormone Activity

  • Amount of time for onset of hormonal effects varies
  • Duration of effects may drop with blood levels or linger for hours
• Interaction of Hormones at Target Cells

  • Permissiveness - Hormone A can only exert full effects if Hormone B is present
  • Synergism - 2 hormones exert same influence, amplify each other
  • Antagonism - One hormone counteracts the other
• Posterior Pituitary

  • Oxytocin - made in hypothalamus, peptide - 9 amino acids long
  • Oxytocin & Positive Feedback - uterine contractions, breastfeeding
• GH Hypo/hypersecretion

  Hypersecretion - usually anterior pituitary tumor

  Kids - gigantism

  Adults - acromegaly
• Disorders of pituitary growth hormone

  Hyposecretion of GH

  Kids - pituitary dwarfism

  Adults - no problems
• Growth Hormone

  • Barry Bonds - before and after illegal doping
• Hyposecretion of TH

  Myxedema - symptoms include low metabolic rate, thick and/or dry skin, puffy eyes, feeling chilled, constipation, edema, mental sluggishness, lethargy

  If due to lack of iodine, a goiter may develop
• TH hypo/hypersecretion

  Hypothyroid in infants leads to cretinism - symptoms include intellectual disabilities, short and disproportionately sized body, thick tongue and neck

  Hypersecretion of TH: most common type is Graves' disease - symptoms include elevated metabolic rate, sweating, rapid and irregular heartbeats, nervousness, and weight loss despite adequate food

  Exophthalmos
• Cortisol disorders

  Hypersecretion - Cushing's disease, Iatrogenic Cushing's syndrome (corticosteroids)

  Hyposecretion - Adrenal insufficiency, Addison's disease
• Male & Female Reproductive Systems Functions

  • Form gametes
  • Bring gametes together
  • Combine genetic info from gametes
  • Support fetal development & birth
• Hormonal Regulation

  HPG axis - Hypothalamus (GnRH) -> Anterior pituitary (FSH & LH) -> Gonads (Males - testosterone, inhibin; Females - estrogens, progesterone, inhibin)

  Becomes active at puberty

  Before puberty: hypothalamus very sensitive to sex hormones, shut off by negative feedback
• Semen

  ~40-750 million sperm (~10% of total volume)

  Provides transport medium, nutrients, protective and activating chemicals (pH 7.2-8.0, prostaglandins)

  Coagulates ~5 mins after ejaculation, re-liquefies soon afterward
• Male Sexual Response

  Penis = male copulatory organ

  Erection - 1st stage, parasympathetic reflex releases nitric oxide (NO), dilates arterioles, erectile tissue fills with blood, compresses drainage veins

  Ejaculation - 1st stage: all fluids move into urethra, internal bladder sphincter contracts

  2nd stage: sympathetic spinal reflex, skeletal muscle at base of erectile tissue contracts rhythmically, semen is propelled at ~11 mph

  Ejaculatory event = orgasm

  Refractory period and resolution follow
• Erectile dysfunction


  Usually insufficient nitric oxide

  Causes include alcohol, psych factors, antidepressants, BP meds, chronic health issues (diabetes, stroke, atherosclerosis, varicose veins)
• Spermatogenesis


  Continuous from puberty to death

  In seminiferous tubules - spermatogonia, sustentocytes, myoid cells, interstitial cells

  90 million sperm/day
• Sustentocytes


  Bound together by tight junctions, form blood testis barrier

  Monitor sperm health, produce regulatory proteins (ABP, inhibin), move cells along to the lumen
• Hormonal Regulation - Male

  HPG axis: GnRH -> FSH and LH -> Testosterone

  During fetal period, testosterone causes development of male structures

  Testosterone levels fall after birth, rise again at puberty

  Testosterone accounts for development/growth of secondary sex characteristics
• Testosterone


  Secondary sex characteristics - pubic, axillary and facial hair, torso hair on some, enlarged larynx (Adam's apple), thickened skin and acne

  Also accounts for more muscle mass in men vs. women, greater bone density, more erythrocytes
• Ovarian cycle - monthly events associated with egg maturation


  From primordial follicle to ovulation - ~300 days

  Handful are recruited every month

  Follicular phase - dominant follicle is selected, secretes estrogen, ends with ovulation (day 14-ish) due to surge of LH

  Luteal phase - corpus luteum is active, progesterone and estrogens support stratum functionalis, from ovulation until beginning of menses (day 14-28)

  28-day cycle in only ~10-15% of females

  Length of follicular phase can vary, but luteal phase is always 14 days
• Hormonal Regulation - Ovarian Cycle


  GnRH stimulates FSH & LH (day 1)

  FSH stimulates follicles, dominant follicle grows, releases estrogens and inhibin

  Estrogen levels rise, inhibits GnRH, inhibin decreases FSH levels

  High estrogen from follicle hits a threshold, briefly exerts positive feedback effect, LH surges, triggers ovulation (day 14)

  Corpus luteum forms, secretes estrogen & progesterone
• Uterine (Menstrual) Cycle


  Divided into 2 phases - follicular and luteal