Hormones

Chemical messengers

Released into the blood and having an effect outside the tissue that made it

Source

Endocrine (ductless) glands

• “Regular” endocrine tissue — glandular epithelium
• Neurosecretory tissue — modified neurons

Target concept

Target cells, target tissues, target organs

Receptors (specific to a particular hormone)

Signal transduction

Pathway

Gland Blood Target tissue (receptor)

Two categories

Steroid — lipids derived from cholesterol

Nonsteroid

• Protein
• Glycoprotein
• Peptide
• Amine (derived from amino acids)

 

Prostaglandins (PGs)

Lipids (fatty acids)

Have LOCAL effects, but are regulatory chemicals carried in the blood, so they are sometimes called “tissue hormones”

• Paracrine agents or “hormones”
  • Substances that regulate other cells in the same tissue
• Autocrine agents or “hormones”
  • Substances that regulate the same cell that produced it
• Endocrine hormone
  • Substances that regulate cells outside the tissue that produced it
  • Classical definition of hormone (one that we’ll use in our course)

Mechanisms of hormone actions

Steroid hormones

Lipid hormones derived from cholesterol

• Examples— testosterone, estrogens (e.g., estradiol), progesterone, aldosterone, cortisone

Mobile receptor model (nuclear receptor model)

• Steroid hormone travels in blood plasma (hormone is temporarily bound to a plasma protein)
• Hormone dissolves through phospholipid bilayer of plasma membrane of target cell
• Hormone binds to receptor inside cell (probably in nucleus), forming hormone-receptor complex
• Hormone-receptor complex triggers the activation of a particular gene (on nuclear DNA)
• mRNA is transcribed at the activated gene
• protein is made using the gene encoded in the new mRNA
• protein causes the hormonal effect

Nonsteroid hormones (peptides, proteins)

Membrane-bound receptors (face out of the target cell)

• May move into cell if small enough
• Second messenger systems
  • cyclic AMP
    • Hormone travels in blood plasma
    • Hormone binds to its receptor in the plasma membrane
      • GPCR (G-protein coupled receptor)
    • Hormone-receptor binding activates a G protein (in plasma membrane)
    • Activated G protein in turn activates the enzyme adenyl cyclase
    • Adenyl cyclase causes ATP to lose two P, becoming cAMP (cyclic AMP [adenosine monophosphate])
    • cAMP activates protein kinases (enzymes that activate other proteins/enzymes), producing the hormonal effect
• Ca⁺⁺-calmodulin
  • hormone travels in blood plasma
  • hormone binds to its specific receptor in the plasma membrane
  • hormone-receptor binding activates G protein, then adenyl cyclase, then protein kinases
  • activated protein kinase opens Ca⁺⁺ channels in plasma membrane
  • Ca⁺⁺ diffuses into target cells (remember, cells HATE calcium, so all the Ca⁺⁺ was outside the cell to begin with)
  • Ca⁺⁺ binds to calmodulin inside cell
  • Ca⁺⁺-calmodulin complex activates (or inactivates) an enzyme, producing the hormonal effects
• Many drugs are targeted at G-protein-coupled receptors (GPCRs)—about 25% of the top-selling drugs and more than half of all currently used drugs.

Amino acid derivative hormones, such as thyroid hormone, may have intracellular receptors as do steroid hormones

Hormones may work together to regulate target cells

Synergistic effects— combined effect is greater than sum of individual effects

Permissive effects— one hormone allows another hormone to have its full effect

Agonistic effects— two hormones have similar effects

Antagonistic effects— two hormones have opposing effects

Trop(h)ic effects— hormones stimulate development of another gland and secretion of that gland’s hormones

Hormones have diverse functions

Even though our course focuses on one or two main actions for each hormone, each hormone may have hundreds of secondary effects

Important for understanding the complexity of endocrine function

Not all hormones find their targets

Metabolized or excreted

Clinically useful — blood or urine analysis shows hormone levels

 

Regulation of receptors

Up regulation

• Target cells increase their number of a particular hormone receptor, becoming more sensitive to that hormone

Down regulation

• Target cells decrease their number of a particular hormone receptor, becoming less sensitive to that hormone

Receptor turnover

• Ongoing process of a cell moving receptors to its plasma membrane or nucleus and removing other receptors, all occurring at rates that can be increased or decreased under different conditions

 

Regulation of secretion

Basal secretion (may be periodic)

• Increase or decrease via feedback controlling mechanisms
  • Feedback
    • Negative; positive
    • Long loop; short loop

Responsive

Cyclic secretion of hormones during female reproductive cycle.
Values plotted from a human study.
Click for a larger image.

Hypothalamus-pituitary

Neuroendocrine cells

Neurons that release their transmitters directly into the blood (rather than across a gap to another neuron), so the transmitters then act as hormones

Hypothalamus

Part of brain on inferior side, just in front of (and above) the brain stem

Part of it is nervous tissue, part is neuroendocrine tissue

Pituitary

Also called hypophysis or hypophysis cerebri

Divided into two parts — anterior pituitary and posterior pituitary

Anterior pituitary (adenohypophysis)

• “regular” endocrine tissue
• Releasing hormones (and release-inhibiting hormones)from the hypothalamus regulate anterior pituitary secretion
  • Hypophyseal portal system
• Major hormones
  • Pr (prolactin)
  • GH (growth hormone)
  • Tropic hormones (trigger development of/secretion by other glands)
  • ACTH (adrenocorticotropic hormone)
  • TSH (thyroid-stimulating hormone)
  • LH (luteinizing hormone)
  • FSH (follicle-stimulating hormone)

Posterior pituitary (neurohypophysis)

• Neuroendocrine cells
  • Body of cell is in hypothalamus
  • Fiber extends from each neuron cell body through the stalklike infundibulum and down into posterior pituitary
  • Thus, posterior pituitary hormones are made in the hypothalamus but released from the posterior pituitary
• Oxytocin and ADH (antidiuretic hormone)

Location of hypothalamus and pituitary

Thyroid

Location — below larynx, wrapped around trachea

Structure

• Two lateral masses and isthmus
• Thyroid follicles
  • Follicular cells — release thyroid hormone
    • Thyroid colloid — stores thyroid hormone
    • Thyroid hormone
      • T3 — triiodothyronine
      • T4 — tetraiodothyronine
• Parafollicular cells
  • Calcitonin

 

Parathyroid

Location

• Imbedded in posterior surfaces of thyroid

Structure

• 4-5 small round bodies made of glandular epithelium

Hormone — parathyroid hormone (PTH)

 

Adrenal

Also called suprarenal

Location

• On top of each kidney (renal = “kidney”)

Structure

• Cortex (endocrine)
  • Zona glomerulosa
    • Mineralocorticoids (aldosterone)
  • Zona fasciculata
    • Glucocorticoids (cortisone)
  • Zona reticularis
    • Glucocorticoids (cortisone)
    • Gonadocorticoids (testosterone, estrogens)
• Medulla (neurosecretory)
  • Catecholamines (epinephrine[adrenaline])

Pancreas

Location

• Lies within the C of the duodenum, inferior to the stomach

Structure

• Pancreatic islets (of Langerhans) (endocrine)
  • Alpha cells (A) — glucagon
  • Beta cells (B) — insulin
  • Delta cells (D) — somatostatin|
  • PP cells (F) — pancreatic polypeptide
  • Epsilon (E) — ghrelin
• Acinar cells (exocrine)

 

Other endocrine glands

Ovaries

Estrogens and progesterone

Testis

Testosterone

Placenta

Human chorionic gonadotropin (HCG)

Estrogens

Progesterone

Placental lactogen

Thymus

Thymosin

GI (gastrointestinal) mucosa

Several hormones regulate GI function

Heart

Atrial natriuretic hormone (ANH)

Pineal

Melatonin

Please refer to the tables in the Anatomy & Physiology textbook for a summary of these and other additional hormones of the human body.

Example of homeostatic endocrine regulation

Calcium concentration in blood plasma

• Parathyroid hormone (PTH) increases blood Ca⁺⁺ by increasing rate of Ca⁺⁺ breakdown (reabsorption) in bone tissue and by increasing rate of Ca⁺⁺ in digestive tract
• Calcitonin (CT; from thyroid) decreases blood Ca⁺⁺ by decreasing rate of reabosorption of calcium in bone tissue