BIOL 2402 Chapter 16 - Endocrine System Part 1

Overview of the Endocrine System

• The endocrine system works alongside the nervous system to coordinate and integrate the activities of body cells.

• It influences metabolic activities using hormones that are transported through the blood.

• Compared to the nervous system, endocrine responses are slower but tend to be longer-lasting.

• Endocrinology is defined as the study of hormones and endocrine organs.

• The endocrine system is responsible for controlling and integrating the following:

  • Reproduction.

  • Growth and development.

  • Maintenance of electrolyte, water, and nutrient balance in the blood.

  • Regulation of cellular metabolism and energy balance.

  • Mobilization of body defenses.

Endocrine Organs and Glands

• Primary endocrine glands include the pituitary, thyroid, parathyroid, adrenal, and pineal glands.

• The hypothalamus is considered a neuroendocrine organ because it has neural functions and produces hormones.

• Several organs possess both exocrine and endocrine functions: the pancreas, gonads, and placenta.

• Other tissues and organs involved in hormone production include:

  • Adipose cells.

  • Thymus.

  • Cells within the walls of the small intestine, stomach, kidneys, and heart.

• Exocrine Glands vs. Endocrine Glands:

  • Exocrine glands produce non-hormonal substances (such as sweat or saliva) and utilize ducts to carry secretions to a membrane surface.

  • Endocrine glands produce hormones and lack ducts, secreting directly into the surrounding tissue fluid and blood.

Chemical Messengers and Hormone Chemistry

• Hormones: Long-distance chemical signals that travel through the blood or lymph.

• Autocrines: Chemicals that exert effects on the same cells that secrete them.

• Paracrines: Locally acting chemicals that affect cells other than those that secrete them.

• Note: Autocrines and paracrines are considered local chemical messengers and are not part of the formal endocrine system.

• Hormone Classification:

  1. Amino acid-based hormones: Includes amino acid derivatives, peptides, and proteins.

  2. Steroid hormones: These are synthesized from cholesterol and include gonadal and adrenocortical hormones.

Mechanisms of Hormone Action

• Hormones circulate systemically, but they only affect target cells—tissues equipped with specific receptors for that hormone.

• Potential consequences of hormone action on target cells include:

  1. Altered plasma membrane permeability or membrane potential by opening/closing ion channels.

  2. Stimulation of the synthesis of enzymes or other proteins.

  3. Activation or deactivation of enzymes.

  4. Induction of secretory activity.

  5. Stimulation of mitosis.

• Binding Mechanisms:

  1. Water-soluble hormones: Include all amino acid-based hormones except thyroid hormone. They cannot enter the cell and must act on plasma membrane receptors via G protein second messengers.

  2. Lipid-soluble hormones: Includes steroid and thyroid hormones. They can enter the cell and act on intracellular receptors that directly activate genes.

Plasma Membrane Receptors and the Second-Messenger System

• Amino acid-based hormones (except thyroid hormone) exert effects via second-messenger systems.

• The two main systems are the Cyclic AMP (cAMP) and PIP$_2$-calcium systems.

• cAMP Signaling Mechanism:

  1. Hormone (1st messenger) binds to the receptor.

  2. The receptor activates a G protein ($G_s$).

  3. The G protein activates the enzyme adenylate cyclase.

  4. Adenylate cyclase converts ATP to cAMP (2nd messenger).

  5. cAMP activates protein kinases that phosphorylate various proteins, activating some and u others.

• Amplification: Intracellular enzymatic cascades have a huge amplification effect; cAMP is rapidly degraded by the enzyme phosphodiesterase.

Intracellular Receptors and Direct Gene Activation

• Lipid-soluble hormones (steroids and thyroid hormone) diffuse into target cells and bind with intracellular receptors.

• The receptor-hormone complex enters the nucleus and binds to a specific region of DNA.

• This binding initiates DNA transcription to produce mRNA.

• The mRNA is translated into a specific protein, which may be used for metabolic activities, structural purposes, or export.

Regulation of Hormone Release

• Blood levels of hormones are primarily controlled by negative feedback systems, maintaining levels within a narrow desirable range.

• Hormone release is triggered by three types of stimuli:

  1. Humoral Stimuli: Changing blood levels of ions and nutrients stimulate secretion. Example: Low Ca$^{2+}$ in the blood stimulates the parathyroid glands to secrete Parathyroid Hormone (PTH), which increases blood Ca$^{2+}$.

  2. Neural Stimuli: Nerve fibers stimulate release. Example: Sympathetic nervous system fibers stimulate the adrenal medulla to secrete catecholamines (epinephrine and norepinephrine).

  3. Hormonal Stimuli: Hormones stimulate other endocrine organs to release their hormones. This often involves a hypothalamic-pituitary-target endocrine organ feedback loop.

• Nervous System Modulation: The nervous system can override normal endocrine controls. For instance, under severe stress, the hypothalamus and sympathetic nervous system override insulin to increase blood glucose for "fight or flight" responses.

Target Cell Specificity and Hormone Half-Life

• Target cell activation depends on blood levels of the hormone, the relative number of receptors, and the affinity (binding strength) between the receptor and hormone.

• Receptor Regulation:

  • Up-regulation: Target cells form more receptors in response to low hormone levels.

  • Down-regulation: Target cells lose receptors in response to high hormone levels to prevented overreaction.

• Circulation and Removal:

  • Steroids and thyroid hormones are bound to plasma proteins; others circulate freely.

  • Hormones are removed by degrading enzymes, the kidneys, or the liver.

  • Half-life: The time required for a hormone's blood level to decrease by half, ranging from a fraction of a minute to a week.

• Interaction Types:

  1. Permissiveness: One hormone cannot exert its full effect without another being present (e.g., reproductive hormones need thyroid hormone).

  2. Synergism: More than one hormone produces the same effects, causing amplification (e.g., glucagon and epinephrine both releasing glucose).

  3. Antagonism: One hormone opposes the action of another (e.g., insulin and glucagon).

The Pituitary Gland and Hypothalamus

• The pituitary gland (hypophysis) is connected to the hypothalamus by the infundibulum.

• Two Major Lobes:

  1. Posterior Pituitary (Neurohypophysis): Neural tissue derived from brain downgrowth. It maintains a neural connection via the hypothalamic-hypophyseal tract. It stores and releases neurohormones produced in the hypothalamus.

  2. Anterior Pituitary (Adenohypophysis): Glandular tissue connected vascularly via the hypophyseal portal system (primary capillary plexus, hypophyseal portal veins, and secondary capillary plexus).

• Posterior Pituitary Hormones:

  • Oxytocin: Stimulates uterine contractions during childbirth and triggers milk ejection (letdown reflex) via positive feedback. Produced in the paraventricular nucleus.

  • Antidiuretic Hormone (ADH): Produced in the supraoptic nucleus. Stimulated by high blood solute concentration (monitored by hypothalamic osmoreceptors) or low blood pressure. It targets kidney tubules to reabsorb water. Inhibited by alcohol and diuretics.

  • Hyposecretion of ADH results in Diabetes insipidus; hypersecretion results in Syndrome of Inappropriate ADH secretion (SIADH).

• Anterior Pituitary Hormones:

  • Growth Hormone (GH): Has direct metabolic effects (increasing fatty acids, glucose-sparing, glycogenolysis) and indirect growth-promoting effects via Insulin-like growth factors (IGFs) targeting bone and skeletal muscle.

    • Hypersecretion: Gigantism in children (up to 8 feet); Acromegaly in adults (overgrowth of hands, feet, face).

    • Hyposecretion: Pituitary dwarfism in children (as low as 4 feet).

  • Thyroid-stimulating Hormone (TSH): A tropic hormone stimulated by Thyrotropin-releasing hormone (TRH). It promotes thyroid development and secretion.

  • Adrenocorticotropic Hormone (ACTH): Stimulated by Corticotropin-releasing hormone (CRH). Peak levels occur in the morning. Triggers the release of corticosteroids from the adrenal cortex.

  • Gonadotropins (FSH and LH): Stimulated by Gonadotropin-releasing hormone (GnRH) after puberty. FSH stimulates gamete production. LH promotes gonadal hormone production, ovulation, and testosterone production.

  • Prolactin (PRL): Stimulates milk production. Primarily controlled by Prolactin-inhibiting hormone (PIH/dopamine). Hypersecretion causes galactorrhea, cessation of menses, or impotence.

The Thyroid Gland

• Anatomy: Butterfly-shaped, located in the anterior neck. It consists of two lobes connected by an isthmus. It contains follicles (follicular cells producing thyroglobulin and colloid containing iodine) and parafollicular cells (producing calcitonin).

• Thyroid Hormone (TH): The body's major metabolic hormone. Two forms:

  • T$_4$ (Thyroxine): 4 iodine atoms.

  • T$_3$ (Triiodothyronine): 3 iodine atoms; 10 times more active than T$_4$.

• Effects: Increases basal metabolic rate (BMR) and heat production (calorigenic effect), regulates tissue growth/development, and maintains blood pressure.

• Homeostatic Imbalances:

  • Hyperthyroidism: Graves' disease is most common. An autoimmune condition where antibodies mimic TSH. Symptoms: high BMR, sweating, rapid heart rate, weight loss, and exophthalmos (bulging eyes).

  • Hypothyroidism: In adults, leads to myxedema (low BMR, puffiness, lethargy). A lack of iodine can cause a goiter (enlarged thyroid) as the gland produces unusable thyroglobulin.

• Calcitonin: Produced by parafollicular cells in response to high blood Ca$^{2+}$. It inhibits osteoclast activity and stimulates Ca$^{2+}$ incorporation into the bone matrix.

The Parathyroid Glands

• Typically four to eight tiny glands on the posterior of the thyroid.

• Produce Parathyroid Hormone (PTH), the most important hormone for Ca$^{2+}$ homeostasis.

• PTH Action: Increases blood Ca$^{2+}$ by targeting the skeleton (bone resorption), kidneys (reabsorption), and intestine (activation of vitamin D).

• Clinical Imbalances:

  • Hyperparathyroidism: Often caused by a tumor; leads to softened/deformed bones and kidney stones.

  • Hypoparathyroidism: Results in hypocalcemia, tetany, respiratory paralysis, and death.

The Adrenal Glands

• Paired organs on top of the kidneys (suprarenal glands).

• Adrenal Cortex (Outer): Glandular tissue secreting corticosteroids. Layers:

  1. Zona glomerulosa: Produces mineralocorticoids (e.g., Aldosterone) to regulate Na$^+$ and K$^+$. Aldosterone release is stimulated by the Renin-angiotensin-aldosterone mechanism, high K$^+$, and ACTH; it is inhibited by Atrial Natriuretic Peptide (ANP).

  2. Zona fasciculata: Produces glucocorticoids (e.g., Cortisol/Hydrocortisone). Glucocorticoids facilitate gluconeogenesis (forming glucose from fats/proteins) and have a glucose-sparing effect for the brain. Excessive levels depress the immune system and inhibit inflammation.

  3. Zona reticularis: Produces gonadocorticoids (weak androgens like DHEA). These contribute to puberty, sex drive in women, and postmenopausal estrogen.

• Adrenal Medulla (Inner): Part of the sympathetic nervous system. Medullary chromaffin cells secrete catecholamines (80% epinephrine, 20% norepinephrine). This mediates the short-term stress response (increased heart rate, blood pressure, and blood glucose).

• Imbalances:

  • Cushing’s Syndrome: Hypersecretion of glucocorticoids. Symptoms: "moon face," "buffalo hump," and hyperglycemia.

  • Addison’s Disease: Hyposecretion of glucocorticoids and mineralocorticoids. Symptoms: weight loss, dehydration, and hypotension.

The Pancreas and Glucose Regulation

• The pancreas is a mixed gland behind the stomach. Exocrine acinar cells produce digestive juice. Endocrine pancreatic islets (islets of Langerhans) contain:

  • Alpha ($\alpha$) cells: Produce glucagon (hyperglycemic hormone).

  • Beta ($\beta$) cells: Produce insulin (hypoglycemic hormone).

• Insulin: Lower blood glucose by enhancing membrane transport into cells, catalyzing glucose oxidation for ATP, and promoting glycogenesis (glucose to glycogen) and lipogenesis (glucose to fat).

• Glucagon: Raises blood glucose by targeting the liver for glycogenolysis (glycogen breakdown) and gluconeogenesis.

• Diabetes Mellitus (DM):

  • Type 1: Absence of insulin. Type 2: Insulin hypoactivity.

  • Signs: Polyuria (high urine output), Polydipsia (thirst), Polyphagia (hunger).

  • Complications: Glycosuria, lipidemia, ketoacidosis (build-up of acidic ketones), and ketonuria.

• Hyperinsulinism: Excessive insulin causing hypoglycemia (anxiety, disorientation, death).

Other Endocrine Organs

• Pineal Gland: Secretes melatonin (derived from serotonin) to regulate day/night cycles and sexual maturation.

• Ovaries: Produce estrogens (maturation and secondary characteristics) and progesterone (breast development and uterine cycle).

• Testes: Produce testosterone (sperm production, male characteristics, sex drive).

• Placenta: Produces estrogens, progesterone, and human chorionic gonadotropin (hCG).

• Adipose Tissue: Releases leptin (appetite control).

• Gastrointestinal Tract: Enteroendocrine cells secrete gastrin, secretin, and cholecystokinin (CCK).

• Heart: Secretes Atrial Natriuretic Peptide (ANP) to decrease blood pressure.

• Kidneys: Secrete Erythropoietin (RBC production) and Renin.

• Skin: Produces Cholecalciferol (precursor to vitamin D); Calcitriol is the active form.

• Thymus: Produces thymulin, thymopoietins, and thymosins for T lymphocyte development.

The correct answer is growth hormone (GH).

Here is why:

• Tropic hormones are hormones that target other endocrine glands to regulate their hormone secretion. According to your notes, the tropic hormones produced by the anterior pituitary are TSH, ACTH, FSH, and LH.

  • ACTH targets the adrenal cortex (an endocrine gland) to release corticosteroids.

  • FSH and LH (gonadotropins) target the gonads (ovaries and testes, which are endocrine organs) to stimulate sex hormone release and gamete production.

• Growth hormone (GH) is not a tropic hormone. Rather