Lecture day 2 Endocrine June 5th

Hormone Classes

• Hormones are divided into two major classes based on water solubility.

• Water solubility affects how the body handles, makes, shifts, and moves hormones.

• The major division is between water-soluble and water-insoluble hormones.

• This division is not a continuum but rather two separate groups.

• Water solubility is determined by whether the hormone is made from amino acids or cholesterol.

Chemical Basis

• Hormones made from amino acids are typically more water-soluble.

• Hormones made from cholesterol are typically water-insoluble or fat-soluble.

• Amino acid-based hormones can be a single amino acid, two amino acids, a string of amino acids (polypeptide), or multiple polypeptides.

• Steroid hormones are based on cholesterol.

• Examples of steroid hormones include testosterone, estrogen, cortisol, and aldosterone.

• Steroid hormones have a structure of three six-carbon rings with one five-carbon ring, similar to cholesterol.

Solubility and Cell Membrane Interaction

• Water-soluble chemicals are lipid-insoluble, and lipid-soluble chemicals are water-insoluble.

• The cell membrane is made of a phospholipid bilayer with water-insoluble lipid tails.

• Water-soluble hormones cannot pass through the cell membrane.

• Lipid-soluble hormones can pass through the cell membrane.

Mechanism of Action

• Water-Soluble Hormones:

  • Bind to receptors on the cell surface.

  • The hormone itself does not enter the cell.

  • Binding to the receptor triggers a signaling pathway (signal transduction) to send a message inside the cell.

  • This leads to a cellular response, such as changes in metabolism or protein synthesis.

  • Examples of signaling molecules include G protein-coupled receptors, cyclic AMP and calcium compounds.

• Water-Insoluble Hormones:

  • Pass directly through the cell membrane.

  • Receptors are located inside the cell, often in the nucleus.

  • The hormone-receptor complex typically goes to the DNA and acts as a transcription factor.

  • This leads to a response, typically making more of a protein.

Target Cell Specificity

• Target cells must have a receptor for a specific hormone.

• If a cell does not have a receptor, the hormone will not affect it.

• The degree of activation depends on the amount of hormone, the number of receptors, and the strength of binding.

Hormone Regulation

• Endocrine glands release hormones into the blood.

• Hormones travel through the bloodstream and affect target cells with appropriate receptors.

• Endocrine glands can be stimulated by:

  • Neural stimuli: a neuron tells the endocrine gland to make a hormone.

  • Hormonal stimuli: another endocrine gland releases a hormone.

  • Humoral stimuli: a change in extracellular fluid composition.

Negative Feedback

• High blood hormone levels lead to decreased hormone secretion, and vice versa.

• This maintains homeostasis.

• Communication occurs between the endocrine gland and the target cell to regulate the response.

Receptor Regulation

• Downregulation: Increased receptor occupancy leads to reduced receptor expression.

• Upregulation: Decreased receptor occupancy leads to increased receptor expression.

• Downregulation and upregulation help to maintain a correct and homeostatic response.

• The goal is to maintain the response within a normal range.

• Homeostasis is maintained at both the endocrine gland and the target cells.

Receptor Affinity

• Affinity refers to how well a hormone binds to its receptor.

• High affinity leads to an increased response.

• Low affinity leads to a decreased response.

• No affinity means the hormone will not bind, and the cell is not a target cell for that hormone.

Half-Life

• Hormones are removed from the blood over time through degradation by enzymes, metabolism by the liver, and excretion by the kidneys.

• Half-life refers to how quickly a hormone is removed from the blood.

• Short half-life indicates quick removal from the blood.

• Long half-life indicates a longer time circulating in the blood.

Hormone Transport

• Water-soluble hormones dissolve freely in blood.

• Fat-soluble hormones require a carrier protein (globulin) to cover them and make them water-soluble for transport.

• Water-soluble hormones do not need a carrier protein.

Response Times and Duration

• Water-soluble hormones typically have a faster response time and a shorter duration.

• Water-insoluble hormones typically have a longer response time and a longer duration.

Summary of Differences

• Water-Soluble Hormones:

  • Made from amino acids.

  • Shorter duration and response time.

  • No carrier protein.

  • Cell surface receptors.

• Lipid-Soluble Hormones:

  • Made from cholesterol.

  • Longer duration and response time.

  • Require a carrier protein.

  • Intracellular receptors.

Hormone Interactions

• Multiple hormones can act on a target cell simultaneously.

• There are three types of hormone interactions:

  • Synergistic: Hormones add their effects together (e.g., cortisol and glucagon both increase blood glucose levels).

  • Antagonistic: Hormones have opposite effects (e.g., insulin decreases blood glucose, glucagon increases blood glucose; parathyroid hormone increases blood calcium, calcitonin decreases blood calcium).

  • Permissiveness: One hormone is required for another hormone to have an effect. Both hormones must be present for a response from hormone B to occur. A has to be there in order for the response from hormone B to happen.

Hypothalamus and Pituitary Gland

• The hypothalamus controls the autonomic nervous system and the endocrine system.

• The infundibulum connects the hypothalamus to the pituitary gland.

• The hypothalamus physically forms the neurohypophysis (posterior pituitary).

• The adenohypophysis (anterior pituitary) is attached to but not physically part of the hypothalamus.

Hypothalamic-Hypophyseal Tract

• Connects the hypothalamus to the neurohypophysis.

• Neurons in the hypothalamus release oxytocin and antidiuretic hormone (ADH) into the blood in the neurohypophysis.

Adenohypophysis Control

• The hypothalamus controls the adenohypophysis by secreting releasing and inhibiting hormones into a capillary bed.

• These hormones travel through the bloodstream to the adenohypophysis and regulate its hormone release.

• The adenohypophysis makes six hormones.

Releasing and Inhibiting Hormones

• The hypothalamus secretes releasing hormones to stimulate the adenohypophysis and inhibiting hormones to suppress it.

• Examples:

  • Growth hormone-releasing hormone (GHRH) stimulates growth hormone release.

  • Growth hormone-inhibiting hormone (GHIH) inhibits growth hormone release.

  • Thyroid-releasing hormone (TRH) stimulates thyroid-stimulating hormone (TSH) release.

• These hormones are released into the blood and act on the adenohypophysis.

Hypophyseal Portal System

• The adenohypophysis is controlled through the hypophyseal portal system.

• Portal system means that there is an extra capillary bed. Blood goes through a capillary bed, then a vessel, then another capillary bed before returning to the heart.

Neurohypophysis Hormones

Oxytocin

• Stimulates uterine contractions during childbirth.

• Triggers milk ejection (milk letdown) in mammary glands.

• Positive feedback mechanisms.

• Promotes social bonding and connection.

Antidiuretic Hormone (ADH)

• Causes the kidneys to reabsorb more water.

• Released when dehydrated to save water.

• Also known as vasopressin.

• Lack of ADH leads to diabetes insipidus, causing increased urination.

Adenohypophysis Hormones

• The adenohypophysis makes six hormones: Four out of the six hormones are tropic hormones (they control the release of another hormone).

  • Thyroid-stimulating hormone (TSH).

  • Adrenocorticotropic hormone (ACTH).

  • Follicle stimulating hormone (FSH).

  • Luteinizing Hormone (LH).

  • Growth Hormone (GH).

  • Prolactin.

Growth Hormone (GH)

• Regulated by growth hormone-releasing hormone (GHRH) and growth hormone-inhibiting hormone (GHIH).

• Stimulates growth in various tissues, especially bone and muscle.

• Important for growth in children and adolescents.

Growth Hormone Imbalances

• Hypersecretion of GH in children leads to gigantism.

• Hyposecretion of GH in children leads to pituitary dwarfism.

• Acromegaly: hypersecretion of growth hormones in adults.

Thyroid-Stimulating Hormone (TSH)

• Goes to the thyroid gland to make thyroid hormones.

Adrenocorticotropic Hormone (ACTH)

• Goes to the adrenal glands, Tells them to make cortisol.

Gonadotropins- FSH and LH

• Go to the ovaries and the testies.

• Releases the gametes reproductive cells.

Prolactin

• Stimulates milk production in females. Found in males but has no known function.

Thyroid gland

• Made up of follicles, colloid, and parafollicular cells.

Thyroid Hormones

• Two forms: T4 and T3.

• T4 is the major form in circulation.

• T3 is the active form in cells.

• Increase metabolic rate and heat production.

• Regulate growth and development.

Thyroid Hormone Production

1. Iodine is transported from the blood into the follicular cells of the thyroid.

2. Iodine is transported into the colloid.

3. In the colloid, iodine meets with tyrosine.

4. Tyrosine has two seats for iodine:

   • Tyrosine + 2 iodine = DIT

   • Tyrosine + 1 iodine = MIT

5. Two tyrosines + 4 iodine = T4 (most common).

6. Two tyrosines + 3 iodine = T3 (more active).

7. T3 and T4 get shipped into the blood.

• T3 is 10 times as active as T4.

• T4 is the transport version of the hormone.

1. T4 gets into the cell, then it is converted into T3.

• Exception: Amino acid-based steroid hormones, such as t3 and t4, follow all of the rules of steroids. Has globulin, has intercellular receptor, has long response time, and has a long duration of activity and half life.

Thyroid Hormone Imbalances

• Hypothyroidism: Not enough thyroid hormone.

  • Lack of iodine in the diet.

• Hyperthyroidism (Graves' disease): Making too much thyroid hormone.

Calcitonin

• Also made by the thyroid gland. It Comes from parafollicular cells.

• Seems to not do anything but tells osteoclasts to slow down.

Parathyroid Gland

• Located on the posterior side of the thyroid.

• Makes parathyroid hormone (PTH).

• Humorally stimulated by the monitoring blood calcium levels.

• Decreasing calcium levels causes the parathyroid gland to secrete PTH.

• PTH tells osteoclasts to chew up more bone, releasing calcium into the blood.

• If PTH is constant, you end up with osteoporosis, in which case your bones don't get as strong.

• So it increases blood calcium by stimulating the bones.

• You need blood calcium for you to live so your body will sacrifice your elderly years for the goal of surviving till tomorrow.

Adrenal Glands

• The adrenal gland is Two regions: The cortex and the medulla.

• The medulla is nervous tissue and releases epinephrine and norepinephrine into the blood, so they are hormones.

• The adrenal cortex contains Three layers, called a zonas: zona glomerulosa, zona fasciculata, zona reticularis.

• Each zone synthesizes different classes of steroid hormones: mineralocorticoids, glucocorticoids, and gonadocorticoids.

• mineralocorticoid: Regulates the election concentration so mostly regulates to sodium and potassium in the extracellular space.

• glucocorticoids (cortisol): involved in Blood Sugar regulation along with a lot of other things.

• gonadocorticoids: They were named because they are steroid hormones (THE FIRST ONES WE SAW). Gonadocorticoids function as precursors for testosterone as well as affect those receptors.

Mineralocorticoids

• Regulate electrolyte concentration, mostly sodium and potassium.

• Make more sodium and reabsorbed from the water in the kidneys.

• aldosterone is the most powerful, the most important, and the most common mineralocorticoid. It Increases the sodium and potassium levels in the blood.

Sodium & Water Balance

• THE BODY DOES NOT REALLY CONTROL WATER.

THE BODY CAN CONTROL SODUIM. YOU CAN THING OF WATER FOLLOWING SODIUM.Wherever water goes, volume increases. Wherever volume increases, pressure increases.