Mechanisms of Hormonal Regulation

Chapter 21: Mechanisms of Hormonal Regulation

Chapter Objectives

  • Identify functions of the endocrine system.

  • Identify the general characteristics of hormones.

  • State the criteria for the classification of hormones.

  • Classify hormones based on their structure.

  • Discuss the regulation of hormone secretion by feedback loops with attention to short, long, and ultra-short loops.

  • Compare the transport of lipid-soluble and water-soluble hormones.

  • State the three general responses of a cell to the binding of a hormone.

  • Compare upregulation and downregulation.

  • Describe the mechanism of action for lipid-soluble hormones.

  • Describe the mechanism of action for water-soluble hormones.

  • Discuss the vital importance of the hypothalamus to pituitary function.

  • Describe the anatomic connection of the anterior pituitary to the hypothalamus.

  • Describe the anatomic relationship of the posterior pituitary to the hypothalamus.

  • List the hormones produced by the hypothalamus, focusing on their controls, target tissues, and actions.

  • Characterize the target tissues and actions of hypothalamic hormones.

  • Illustrate the anatomy and location of the thyroid gland.

  • List the hormones released from the anterior pituitary and characterize their actions and target tissues.

  • Characterize the location of release and actions of calcitonin.

  • Diagram the formation, storage, and release of thyroid hormones.

  • Discuss the similarities and differences of thyroid hormones.

  • Discuss the number, location, and function of the parathyroid glands.

  • Discuss the action of parathyroid hormone (PTH) and its relation to blood calcium levels.

  • Compare the endocrine and exocrine functions of the pancreas.

  • Describe the histology and location of the pancreas.

  • Identify the hormones secreted by the alpha, beta, and delta cells of the pancreas.

  • Explain the effect of insulin on blood glucose levels and its anabolic actions.

  • Describe the effect of glucagon on blood glucose levels.

  • Discuss the possible functionality of pancreatic somatostatin.

  • Describe the location, anatomy, and histology of the adrenal glands.

  • Discuss the control mechanisms for hormone release from the adrenal cortex.

  • Describe the controls and effects of glucocorticoids.

  • Describe the controls and effects of mineralocorticoids.

  • Discuss the histology, hormones, and functions of the hormones of the adrenal medulla.

  • Describe tests used to evaluate endocrine functions.

Mechanisms of Hormonal Regulation

Functions of the Endocrine System

  • Differentiation of the reproductive and central nervous systems in the developing fetus.

  • Stimulation of sequential growth and development during childhood and adolescence.

  • Coordination of the male and female reproductive systems.

  • Maintenance of an optimal internal environment (homeostasis).

  • Initiation of corrective and adaptive responses during emergency demands (stress responses).

General Characteristics of Hormones

  • Hormones are chemical messengers released by glands.

  • Specific rates and rhythms of secretion: Diurnal or circadian, pulsatile and cyclic patterns depending on circulating substrates.

  • Hormones operate within feedback systems (positive and negative).

  • Affect only cells with appropriate receptors; target specificity.

  • Hormones are inactivated by the liver or directly excreted by the kidneys.

Regulation of Hormone Release

  • Hormones are released in response to changes in the cellular environment.

  • Their release helps maintain regulated levels of certain substances or other hormones.

  • Regulation can be through chemical, endocrine, or neural factors.

  • Negative feedback: Most common regulation pattern; inhibits secretion.

  • Positive feedback: Enhances secretion in response to certain conditions.

Hormone Transport

  • Hormones are released into the circulatory system by endocrine glands and distributed throughout the body.

  • Water-soluble hormones circulate in free, unbound forms.

  • Lipid-soluble hormones are mainly transported bound to carrier or transport proteins.

Hormone Receptors

  • Target cells recognize and bind hormones with high affinity, initiating a signal.

  • The more receptors present, the more sensitive the cell becomes to hormones.

Upregulation and Downregulation

  • Up-regulation: Low concentrations of hormones increase the number of receptors per cell.

  • Down-regulation: High concentrations of hormones decrease the number of receptors, reducing sensitivity.

Location of Hormone Receptors

  • Receptors can be located in or on the plasma membrane or in the intracellular compartment of target cells.

  • Water-soluble hormones: High molecular weight; cannot diffuse across the plasma membrane.

  • Lipid-soluble hormones: Easily diffuse across the plasma membrane and bind to cytosolic or nuclear receptors.

Signal Transduction Mechanism

  • First messenger: The hormone that carries the message to the target cell.

  • Signal transduction: The process of how the message is communicated inside the target cell.

  • Steps:

    • Receptor activation ('binding of a hormone to its receptor').

    • Activation of a G protein (transducer) and a membrane-associated enzyme (effector enzyme).

    • Production of a second messenger.

    • Activation of intracellular enzymes (e.g., protein kinase A or C).

    • Altered gene transcription resulting in the target cell response to the hormone.

Second Messengers

  • Serve as the initial link between the first signal (hormone) and intracellular actions.

  • Examples include:

    • Cyclic AMP (cAMP): Must activate adenylyl cyclase.

    • Cyclic GMP (cGMP): Activated by guanylyl cyclase.

    • Calcium ions (Ca++): Bind with calmodulin, affecting various physiological responses.

Hormonal Actions

  • Three primary routes stimulate hormone effects:

    • Altering channel-forming proteins to modify membrane channel permeability.

    • Activating preexisting proteins via second messenger systems.

    • Activating genes to initiate protein synthesis.

  • Hormonal effects can be classified as:

    • Direct effects: Immediate actions of hormones.

    • Permissive effects: Enhancement of the effect of another hormone.

Hypothalamic–Pituitary System Structure

  • The hypothalamus and pituitary gland together form the neuroendocrine system.

  • The hypothalamus is crucial in producing releasing or inhibitory hormones and tropic hormones that act on anterior and posterior pituitary glands:

    • Anterior Pituitary (Adenohypophysis)

    • Posterior Pituitary (Neurohypophysis)

Location of the Hypothalamus

  • Located at the base of the brain.

  • Anatomically connected to the anterior pituitary via portal blood vessels.

  • Connected to the posterior pituitary by the hypothalamohypophysial tract (a nerve tract).

Hormones produced by the Hypothalamus

  • Prolactin-inhibiting factor (PIF): Inhibits prolactin secretion.

  • Thyrotropin-releasing hormone (TRH): Stimulates TSH release.

  • Gonadotropin-releasing hormone (GnRH): Stimulates FSH and LH release.

  • Somatostatin: Inhibits growth hormone and insulin secretion.

  • Growth hormone-releasing factor (GRF): Stimulates growth hormone secretion.

  • Corticotropin-releasing hormone (CRH): Stimulates adrenocorticotropic hormone secretion.

  • Substance P: Involved in pain perception and stress responses.

Anterior Pituitary Hormones

  • Corticotropin-related hormones:

    • Adrenocorticotropic hormone (ACTH): Stimulates cortisol release from the adrenal cortex.

    • Melanocyte-stimulating hormone (MSH): Influences pigmentation.

  • Glycoprotein hormones:

    • Thyroid-stimulating hormone (TSH): Stimulates thyroid hormones' release.

    • Follicle-stimulating hormone (FSH): Regulates reproductive processes.

    • Luteinizing hormone (LH): Triggers ovulation and testosterone production.

  • Somatomammotropins:

    • Growth hormone (GH): Stimulates growth and metabolism.

    • Prolactin: Stimulates milk production in lactation.

  • Minor corticotropin hormones:

    • β-lipotropin: Involved in fat metabolism.

    • β-endorphins: Involved in pain relief.

Posterior Pituitary Hormones

  • Hormones synthesized in hypothalamic nuclei, stored in and secreted by the posterior pituitary:

  • Antidiuretic hormone (ADH) (also known as arginine vasopressin):

    • Controls plasma osmolality.

    • Causes water reabsorption into the blood.

    • Released when plasma osmolality increases or intravascular volume decreases.

  • Oxytocin:

    • Stimulates uterine contractions during childbirth.

    • Involved in milk ejection during lactation.

Pineal Gland

  • Located within the brain, consisting of photoreceptive cells that secrete melatonin.

  • Melatonin functions:

    • Regulates circadian rhythms and reproductive systems, including GnRH secretion and onset of puberty.

    • Plays a role in immune regulation and potentially in the aging process.

Thyroid Gland

  • Composed of two lobes lateral to the trachea and connected by an isthmus.

  • Contains follicles (with follicle cells surrounding the colloid) and parafollicular cells (C cells) that secrete calcitonin (which lowers serum calcium levels).

Regulation of Thyroid Hormone Secretion

  • TRH stimulates TSH release.

  • TSH increases:

    • Thyroid hormone release from stored reserves.

    • Iodide uptake and oxidation.

    • Synthesis of thyroid hormones.

    • Prostaglandin synthesis and secretion by thyroid gland.

Thyroid Hormone Production

  • T4 (Thyroxine): Represents 90% of the thyroid hormones.

  • T3 (Triiodothyronine): Represents 10%.

  • Thyroid hormones are bound to:

    • Thyroxine-binding globulin,

    • Thyroxine-binding prealbumin,

    • Lipoproteins,

    • Albumin.

  • Actions of thyroid hormones:

    • Affect growth and maturation of tissues.

    • Regulate cell metabolism, heat production, cardiac functioning, and oxygen consumption.

Parathyroid Glands

  • Small glands located behind the thyroid gland.

  • Produce Parathyroid hormone (PTH) which:

    • Regulates serum calcium levels.

    • Increases calcium concentration in the blood.

    • Decreases phosphate levels.

    • Serves with vitamin D to enhance calcium absorption.

    • Acts as an antagonist to calcitonin.

Parathyroid Hormone-Related Peptide (PTHrP)

  • Exhibits properties similar to PTH and is important for endochondral bone formation and remodeling.

Endocrine Pancreas

  • The pancreas has both endocrine (produces hormones) and exocrine (produces digestive enzymes) functions.

  • Islets of Langerhans:

    • Secretion of glucagon by alpha cells.

    • Secretion of insulin and amylin by beta cells.

    • Secretion of somatostatin and gastrin by delta cells.

    • Secrets pancreatic polypeptide by F cells.

Insulin

  • Regulated by chemical, hormonal, and neural mechanisms; its secretion is promoted by increased blood glucose levels.

  • Facilitates glucose uptake into cells (e.g., through glucose transporter GLUT 4).

  • Functions as an anabolic hormone, synthesizing proteins, carbohydrates, lipids, and nucleic acids.

  • Important Note: Insulin release is stimulated by increased, not decreased, glucose concentrations.

Amylin

  • A peptide hormone secreted with insulin in response to nutrient stimuli.

  • Regulates blood glucose by:

    • Delaying gastric emptying.

    • Suppressing glucagon secretion after meals.

    • Promotes satiety and exhibits antihyperglycemic effects.

Glucagon

  • An insulin antagonist, secreted in response to decreased blood glucose levels.

  • Increases blood glucose by stimulating glycogenolysis and gluconeogenesis, and also stimulates lipolysis.

Pancreatic Somatostatin

  • Produced by delta cells of the pancreas; essential in metabolism of carbohydrates, fats, and proteins.

  • Regulates alpha and beta cell functions by inhibiting insulin and glucagon secretion.

  • Distinct from hypothalamic somatostatin.

Incretins

  • Includes Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP):

    • Control postprandial (after eating) glucose levels by promoting insulin secretion dependent on glucose and inhibiting glucagon synthesis.

    • Also enhance beta-cell mass and replenish intracellular insulin stores.

Gastrin, Ghrelin, and Pancreatic Polypeptide

  • Gastrin: Likely controls glucagon secretion.

  • Ghrelin: Stimulates growth hormone secretion, controls appetite, and regulates insulin sensitivity.

  • Pancreatic polypeptide: Released by PP cells in response to hypoglycemia and protein-rich meals; promotes gastric secretion and antagonizes cholecystokinin.

Adrenal Glands

  • Two pyramid-shaped organs located above the kidneys.

  • The adrenal cortex comprises 80% of the gland’s total weight and has three zones:

    • Zona glomerulosa: Produces mineralocorticoids.

    • Zona fasciculata: Produces glucocorticoids.

    • Zona reticularis: Produces androgens.

  • The adrenal medulla, the inner portion of the gland, secretes catecholamines (epinephrine and norepinephrine).

Functions of the Adrenal Cortex

  • Glucocorticoid hormones (e.g., cortisol, cortisone, cortisone) increase blood glucose, promote protein breakdown, and exert anti-inflammatory effects; they decrease immune response, increasing vulnerability to infections.

  • Mineralocorticoids (e.g., aldosterone) affect ion transport in epithelial cells, causing sodium retention and loss of potassium and hydrogen; regulated by the renin-angiotensin-aldosterone system (RAAS).

  • Adrenal androgens are weak testosterone precursors, converting to stronger forms in peripheral tissues (e.g., testosterone).

Functions of the Adrenal Medulla

  • Chromaffin cells (pheochromocytes) secrete catecholamines, initiating the body's "fight or flight" response and promoting hyperglycemia.

Tests of Endocrine Function

  • Radioimmunoassay (RIA): Measures minuscule quantities of hormones using antibodies and radio-labeled hormones to quantify hormone levels in blood.

  • Enzyme-linked immunosorbent assay (ELISA): A cost-effective and easier alternative to RIA.

  • Bioassay: Employs graded doses of a hormone in a reference preparation, comparing results with an unknown sample.

Aging and the Endocrine System

  • Changes in the endocrine system due to aging can either be a consequence or a cause of aging-related health issues:

Thyroid Gland

  • Glandular atrophy, fibrosis, nodularity, and increased inflammatory infiltrates; associated with lower levels of TSH.

Pancreas

  • Impaired glucose tolerance, diabetes; pancreatic tissue replaced with fat, leading to reductions in insulin secretion and increased insulin resistance.

Growth Hormone (GH) and Insulin-like Growth Factor (IGF)

  • Both decline with aging (termed somatopause), linked to decreases in muscle size, fat and bone mass, and changes in reproductive and cognitive functions.

Parathyroid Glands

  • Changes in calcium balance caused by inadequate intake, malabsorption, or renal alterations.

Adrenal Glands

  • Decreased clearance of cortisol; plasma levels of adrenal androgens gradually decrease with age (adrenopause).

Antidiuretic Hormone (ADH)

  • Increased susceptibility to hyponatremia; syndrome of inappropriate ADH secretion (SIADH) common in the elderly.