Endocrine System Flashcards

Chapter 11: The Endocrine System

General Characteristics of Hormones and Hormonal Control Systems

• The endocrine system is one of the two major control systems of the body, consisting of ductless endocrine glands that secrete hormones, and hormone-secreting cells in various organs.

• Hormones are chemical messengers carried in the blood from their secretion site to target cells.

• Endocrinology involves the structural and functional analysis of hormones.

• Ligand-receptor interactions and cell signaling are crucial for hormone action (review Chapters 3 and 5).

• Hormones functionally link organ systems together by coordinating their functions to maintain homeostasis.

• Most physiological functions are controlled by multiple regulatory systems, often working in opposition.

• Hormone binding to carrier proteins and receptors illustrates the chemistry and physics governing physiological processes.

• The hypothalamus's structure and connection to the anterior pituitary determine its control over anterior pituitary function.

• Regulated iodine uptake by thyroid gland cells exemplifies controlled material exchange between compartments and across cellular membranes.

• Information flow between cells, tissues, and organs is essential for homeostasis and physiological process integration.

11.1 Hormones and Endocrine Glands

• Endocrine glands differ from exocrine glands, which secrete products into ducts that exit the body or enter organ lumens (e.g., sweat glands, intestinal glands).

• Endocrine glands are ductless, releasing hormones into the interstitial fluid, which then diffuse into the blood.

• Hormones reach distant target cells via the bloodstream.

• Figure 11.2 provides an overview of major endocrine glands, hormone secretions, and their functions.

• The endocrine system's components are not anatomically connected but form a functional system.

• Some organs (e.g., the heart) have other functions but contain hormone-secreting cells.

11.2 Hormone Structures and Synthesis

• Hormones fall into three major structural classes: amine hormones, peptide and protein hormones, and steroid hormones.

  • Amine Hormones: Derivatives of tyrosine.

    • Include thyroid hormones (thyroxine (T4) and triiodothyronine (T3)) from the thyroid gland.

    • Catecholamines (epinephrine and norepinephrine) from the adrenal medulla and dopamine from the hypothalamus.

      • Structures are shown in Figure 11.3.

    • T4 is activated to the more potent T3 in target tissues.

    • The adrenal medulla is a modified sympathetic ganglion that secretes catecholamines.

    • It secretes mainly epinephrine, due to high amounts of phenylethanolamine-N-methyltransferase (PNMT), which converts norepinephrine to epinephrine.

    • Dopamine, synthesized by hypothalamic neurons, inhibits certain endocrine cell activity in the pituitary gland via a portal system.

  • Peptide and Protein Hormones: Polypeptides, ranging from short peptides to large glycoproteins.

    • Synthesized as preprohormones on ribosomes, cleaved to prohormones in the rough endoplasmic reticulum (Figure 11.4a).

    • Prohormones are packaged into secretory vesicles by the Golgi apparatus and cleaved into active hormones and other peptides (post-translational modification).

    • Exocytosis releases active hormones and other peptides.

    • Insulin synthesis in the pancreas is a well-studied example (Figure 11.4b).

    • Insulin is processed from preprohormone to prohormone, then cleaved to insulin and C-peptide.

    • Both insulin (key regulator of metabolism) and C-peptide are secreted in equimolar amounts; C-peptide may have actions on various cell types.

  • Steroid Hormones: Derived from cholesterol and primarily produced by the adrenal cortex, gonads, and placenta during pregnancy.

    • Vitamin D is enzymatically converted to an active steroid hormone.

    • Figure 11.5 shows examples of steroid hormones and their structural relationship to cholesterol.

    • Figure 11.6a illustrates the general process of steroid hormone synthesis, which is stimulated by anterior pituitary hormones binding to plasma membrane receptors linked to Gs proteins.

      • Activation of adenylyl cyclase and cAMP production leads to protein kinase A activation, phosphorylating intracellular proteins.

    • The final steroid hormone product depends on the cell type and expressed enzymes.

    • Steroid hormones are not stored in vesicles due to their lipophilic nature, allowing them to diffuse across lipid bilayers into circulation.

    • Bound to carrier proteins (e.g., albumin) in plasma due to poor solubility in blood.

    • Hormones of the Adrenal Cortex

      • The five major hormones are aldosterone, cortisol, corticosterone, dehydroepiandrosterone (DHEA), and androstenedione (Figure 11.6b).

      • Aldosterone is a mineralocorticoid that affects salt balance, mainly in the kidneys (Na+, K+, H+ handling); its production is controlled by angiotensin II.

        • Angiotensin II acts via the inositol trisphosphate second-messenger pathway.

        • Aldosterone stimulates Na+ and H2O retention, and K+ and H+ excretion in the urine.

      • Cortisol and corticosterone are glucocorticoids that affect glucose and organic nutrient metabolism.

        • Cortisol is predominant in humans and facilitates stress responses and regulates the immune system.

      • DHEA and androstenedione are androgens, less potent than testosterone, with functions in adult females, fetuses, and puberty.

      • The adrenal cortex has three layers (Figure 11.7).

      • The zona glomerulosa (outermost layer) synthesizes aldosterone.

      • The zona fasciculata and zona reticularis secrete cortisol and androgens, but not aldosterone.

        • In humans, the zona fasciculata produces cortisol, and the zona reticularis produces androgens.

    • The absence of an enzyme required for cortisol formation can shunt precursors into the androgen pathway, causing congenital adrenal hyperplasia (CAH) and virilization of female fetuses.

    • Hormones of the Gonads

      • Testes and ovaries do not produce aldosterone and cortisol, but express enzymes for androgen pathways.

      • Testes convert androstenedione to testosterone.

      • Ovaries synthesize estrogens (estradiol and estrone) via aromatase-catalyzed conversion of androgens to estrogens (Figure 11.8).

      • Estradiol is the major steroid hormone secreted by the ovaries.

      • Small amounts of testosterone diffuse from ovarian cells, and small amounts of estradiol are produced from testosterone in the testes.

      • Steroid hormones may undergo further conversion in other organs.

      • The corpus luteum secretes progesterone, important for pregnancy maintenance.

        • Progesterone is also synthesized in other parts of the body, such as the placenta. Hormone. Total hormone concentration is the sum of free and bound hormones.

11.3 Hormone Transport in the Blood

• Most peptide and catecholamine hormones are water-soluble and transported dissolved in plasma (Table 11.1).

• Steroid and thyroid hormones are poorly soluble, circulating mainly bound to plasma proteins.

• The concentration of the free hormone is biologically important rather than the concentration of the

11.4 Hormone Metabolism and Excretion

• The Hormone concentration in the blood is regulated after it has acted on a target tissue.

• Hormone concentration in plasma depends on:

  • Its secretion rate by the endocrine gland.

  • Its removal rate from the blood.

• Clearance occurs by excretion or metabolic transformation in the liver and kidneys.

• Hormones can be metabolized by target cells via endocytosis of hormone-receptor complexes.

• Enzymes in blood and tissues rapidly break down catecholamine and peptide hormones, which persist briefly (minutes to an hour).

• Protein-bound hormones are protected from excretion or metabolism, prolonging their circulation (hours to days).

• Metabolism can activate hormones; for example, T4 is converted to active T3 in target cells.

• Figure 11.9 summarizes hormone fates after secretion.

11.5 Mechanisms of Hormone Action

• Hormones reach all tissues via blood, but only target cells respond due to specific receptors.

• Target cell response to hormones aligns with signal transduction pathways for all chemical messengers.

• Water-soluble hormones (peptide hormones and catecholamines) bind to plasma membrane receptors.

• Lipid-soluble hormones (steroid and thyroid hormones) bind to intracellular receptors.

• Hormones regulate receptor numbers via up-regulation (increased receptors from prolonged low hormone concentration) and down-regulation (decreased receptors from high hormone concentration).

• Hormones can also regulate receptors for other hormones.

• Permissiveness: Hormone A must be present for Hormone B to exert its full effect (e.g., thyroid hormone for epinephrine's effect on fatty acid release from adipocytes).

• Figure 11.10 illustrates thyroid hormone's permissive effect on epinephrine-induced fatty acid release.

• Events initiated by hormone-receptor binding:

  • The signal transduction pathways are those used by neurotransmitters and paracrine substances.

• Effects of Peptide Hormones and Catecholamines

  • Receptors are on the extracellular surface of the plasma membrane.

  • Activated receptors influence:

    • The opening or closing of ion channels changes the electrical potential across the membrane.

    • Changes in enzyme activity are usually very rapid and produce changes in the activity of various cellular proteins.

    • Signal transduction pathways lead to transcription of genes.

    • Peptide hormones and catecholamines may exert both rapid (nongenomic) and slower (gene transcription) actions on the same target cell.

• Effects of Steroid and Thyroid Hormone

  • Lipophilic

  • Receptors are intracellular

  • Activating (in some cases, inhibiting) gene transcription

• Pharmacological Effects of Hormones

  • Administration of very large quantities of a hormone for medical purposes may have effects on an individual that are not usually observed at physiological concentrations.

  • Perhaps the most common example is that of very potent synthetic forms of cortisol, such as prednisone, which is administered to suppress allergic and inflammatory reactions. In such situations, a host of unwanted effects may be observed.

11.6 Inputs That Control Hormone Secretion

• Hormone secretion is controlled by three types of inputs to endocrine cells (Figure 11.11):

  • Directly or indirectly by the change in the plasma concentrations of mineral ions or organic nutrients

  • Transmitters released from neurons ending on the endocrine cell

  • Another hormone (or, in some cases, a paracrine substance) acting on the endocrine cell.

• Hormone secretion denotes its release by exocytosis from the cell.

• Control by plasma concentrations of mineral ions or organic nutrients:

  • Secretion of some hormones is directly controlled by plasma concentrations of specific ions or nutrients.

  • Hormones regulate these concentrations through negative feedback (e.g., insulin secretion stimulated by increased plasma glucose, PTH secretion stimulated by decreased plasma Ca2+, as shown in Figure 11.12).

• Control by neurons:

  • The adrenal medulla is stimulated by sympathetic preganglionic fibers.

  • Autonomic nervous system influences other endocrine glands, with inhibitory and stimulatory inputs (Figure 11.13).

• Control by other hormones:

  • The secretion of a particular hormone is directly controlled by the blood concentration of another hormone.

  • A hormone that stimulates the secretion of another hormone is called a tropic hormone.

11.7 Types of Endocrine Disorders

• Features vary based on the hormone affected, but all endocrine diseases can be categorized in one of four ways:

  • Too little hormone (hyposecretion).

  • Too much hormone (hypersecretion).

  • Target-cell hyporesponsiveness.

  • Target-cell hyperresponsiveness.

• Hyposecretion:

  • Primary hyposecretion:

    • Gland not functioning normally.

  • Secondary hyposecretion:

    • Gland is not damaged (at least at first) but is receiving too little stimulation by its tropic hormone.

• Hypersecretion:

  • Primary hypersecretion (the gland is secreting too much of the hormone on its own).

  • Secondary hypersecretion (excessive stimulation of the gland by its tropic hormone).

• Hyporesponsiveness and Hyperresponsiveness

  • The target cells do not respond normally to the hormone: Hyporesponsiveness or hormone resistance.

  • Hyperresponsiveness can also occur and cause problems.

11.8 Control Systems Involving the Hypothalamus and Pituitary Gland

• The pituitary gland (hypophysis) lies in the sella turcica at the brain's base, connected to the hypothalamus by the infundibulum (pituitary stalk).

• The pituitary gland consists of the anterior pituitary gland (adenohypophysis) and the posterior pituitary gland (neurohypophysis).

• Figure 11.14 shows the relationship of the pituitary gland to the brain and hypothalamus and neural and vascular connections between the hypothalamus and pituitary gland.

• Posterior Pituitary Hormones

  • The posterior pituitary is a neural extension of the hypothalamus.

  • Hormones are synthesized in the supraoptic and paraventricular nuclei and transported down axons to the posterior pituitary.

  • Two hormones (oxytocin and vasopressin) are released from axon terminals directly into capillaries.

  • Oxytocin:

    • Stimulates contraction of smooth muscle cells in the breasts, which results in milk ejection during lactation.

    • Stimulates contraction of uterine smooth muscle cells, until eventually the fetus is delivered.

  • Vasopressin:

    • Acts on smooth muscle cells around blood vessels to cause their contraction, which constricts the blood vessels and thereby increases blood pressure.

    • Acts within the kidneys to decrease water excretion in the urine: antidiuretic hormone (ADH).

• Anterior Pituitary Gland Hormones and the Hypothalamus

  • Other nuclei of hypothalamic neurons secrete hormones that control the secretion of all the anterior pituitary gland hormones: hypophysiotropic hormones.

  • With one exception (dopamine), each of the hypophysiotropic hormones is the first in a three-hormone sequence (Figure 11.15).

  • Overview of Anterior Pituitary Gland Hormones

    • 6 hormones:

      • Follicle-stimulating hormone (FSH)

      • Luteinizing hormone (LH)

      • Growth hormone (GH, also known as somatotropin)

      • Thyroid-stimulating hormone (TSH, also known as thyrotropin)

      • Prolactin

      • Adrenocorticotropic hormone (ACTH, also known as corticotropin)

  • Figure 11.16 summarizes the target organs and major functions of the six classical anterior pituitary gland hormones.

    • Thyroid-stimulating hormone induces the thyroid to secrete thyroxine and triiodothyronine.

    • Adrenocorticotropic hormone stimulates the adrenal cortex to secrete cortisol.

    • Growth hormone stimulates the liver to secrete a growth-promoting peptide hormone known as insulin-like growth factor-1 (IGF-1) and, in addition, exerts direct effects on bone and on metabolism.

    • Follicle-stimulating hormone and luteinizing hormone stimulate the gonads to secrete the sex hormones.

    • Prolactin has a major function to stimulate development of the mammary glands during pregnancy and milk production.

  • Hypophysiotropic Hormones

    • Anterior pituitary gland hormones regulated by hormones produced by the hypothalamus, collectively called hypophysiotropic hormones.

    • Secreted by neurons that originate in discrete nuclei of the hypothalamus and terminate in the median eminence (Figure 11.17).

    • Hormone secretion by the anterior pituitary gland is controlled by hypophysiotropic hormones released by hypothalamic neurons that are transported to the anterior pituitary gland by way of the hypothalamo–hypophyseal portal vessels.

    • When an anterior pituitary gland hormone is secreted, it will diffuse into the same capillaries that delivered the hypophysiotropic hormone.

    • The portal circulatory system ensures that hypophysiotropic hormones can reach the cells of the anterior pituitary gland at a high concentration and with very little delay.

    • Two crucial differences, however, distinguish two systems.

      • First, the axons of the hypothalamic neurons that secrete the posterior pituitary hormones leave the hypothalamus and end in the posterior pituitary, whereas those that secrete the hypophysiotropic hormones are much shorter and remain in the hypothalamus, ending on capillaries in the median eminence.

      • Second, most of the capillaries into which the posterior pituitary hormones are secreted immediately drain into the general circulation, which carries the hormones to the heart for distribution to the entire body. In contrast, the hypophysiotropic hormones enter capillaries in the median eminence of the hypothalamus that do not directly join the main bloodstream but empty into the hypothalamo–hypophyseal portal vessels, which carry them to the cells of the anterior pituitary gland.

      • Figure 11.18: Hypophysiotropic hormones impact on the anterior pituitary gland.

        • Secretion of ACTH (corticotropin) is stimulated by corticotropin-releasing hormone (CRH).

        • Secretion of growth hormone is stimulated by growth hormone–releasing hormone (GHRH).

        • Secretion of thyroid-stimulating hormone (thyrotropin) is stimulated by thyrotropin-releasing hormone (TRH).

        • Secretion of both luteinizing hormone and follicle-stimulating hormone (the gonadotropins) is stimulated by gonadotropin-releasing hormone (GnRH).

          • Somatostatin (SST) inhibits the secretion of growth hormone.

        • Dopamine (DA) inhibits the secretion of prolactin.

    • Figure 11.19 summarizes the hypothalamic–anterior pituitary gland system.

  • Neural Control of Hypophysiotropic Hormones

    • Neurons of the hypothalamus receive stimulatory and inhibitory synaptic input from virtually all areas of the central nervous system.

    • The neural inputs to these cells arise from other regions of the hypothalamus, which in turn are linked to inputs from visual pathways that recognize the presence or absence of light.

    • There is a strong circadian influence over the secretion of certain hypophysiotropic hormones.

  • Hormonal Feedback Control of the Hypothalamus and Anterior Pituitary Gland

    • A prominent feature of each of the hormonal sequences initiated by a hypophysiotropic hormone is negative feedback exerted upon the hypothalamo–hypophyseal system by one or more of the hormones in its sequence.

    • The situation described for cortisol, in which the hormone secreted by the third endocrine gland in a sequence exerts a negative feedback effect over the anterior pituitary gland and/or hypothalamus, is known as a long-loop negative feedback (Figure 11.20).

    • The influence of an anterior pituitary gland hormone on the hypothalamus is known as a short-loop negative feedback (see Figure 11.20).

  • The Role of “Nonsequence” Hormones on the Hypothalamus and Anterior Pituitary Gland

    • There are many stimulatory and inhibitory hormonal influences on the hypothalamus and/or anterior pituitary gland other than those that fit the feedback patterns just described.

11.9 Synthesis of Thyroid Hormone

• The thyroid gland produces two iodine-containing molecules of physiological importance, thyroxine (called T4 because it contains four iodines) and triiodothyronine (T3, three iodines; review Figure 11.3).

• A considerable about of T4 is converted to T3 in target tissues by enzymes known as deiodinases.

• Figure 11.21: Location of the bilobed thyroid gland.

• Figure 11.22: Steps involved in T3 and T4 formation.

11.10 Control of Thyroid Function

• The basic control mechanism of TSH production is the negative feedback action of T3 and T4 on the anterior pituitary gland and, to a lesser extent, the hypothalamus (Figure 11.23).

• Figure 11.23: TRH-TSH-thyroid hormone sequence.

• TSH also increases protein synthesis in follicular epithelial cells, increases DNA replication and cell division, and increases the amount of rough endoplasmic reticulum and other cellular machinery required by follicular epithelial cells for protein synthesis.

• An enlarged thyroid gland from any cause is called a goiter.

11.11 Actions of Thyroid Hormone

• Receptors for thyroid hormone are present in the nuclei of most of the cells of the body, unlike receptors for many other hormones, whose distribution is more limited.

• Like steroid hormones, T3 acts by inducing gene transcription and protein synthesis.

• Metabolic Actions:

  • T3 stimulates carbohydrate absorption from the small intestine and increases fatty acid release from adipocytes.

  • Permissive Actions:

    • Some of the actions of T3 are attributable to its permissive effects on the actions of catecholamines.

  • Growth and Development

    • T3 is required for normal production of growth hormone from the anterior pituitary gland. Therefore, when T3 is very low, growth in children is decreased.

11.12 Hypothyroidism and Hyperthyroidism

• Any condition characterized by plasma concentrations of thyroid hormones that are chronically below normal is known as hypothyroidism.

• The most common cause of hypothyroidism in the United States is autoimmune disruption of the normal function of the thyroid gland, a condition known as autoimmune thyroiditis.

• Figure 11.24: Goiter at an advanced stage.

• In severe, untreated hypothyroidism:

  • certain hydrophilic polymers are present.

  • certain hydrophilic polymers:
    As in the case of hypothyroidism, there are a variety of ways in which hyperthyroidism, or thyrotoxicosis, can develop.

11.13 Physiological Functions of Cortisol

• A real or perceived threat to homeostasis.

• Invariably, the secretion from the adrenal cortex of the glucocorticoid hormone cortisol is increased.

• Figure 11.25 is the CRH-ACTH-cortisol pathway.

11.14 Functions of Cortisol in Stress

• Table 11.2 summarizes that the major effects of increased plasma concentration of cortisol during stress influence organic metabolism, enhance vascular reactivity, have protective effects against damaging influences of stress, inhibit inflammation and specific immune responses, and inhibit nonessential functions.

11.15 Adrenal Insufficiency and Cushing’s Syndrome

• Cortisol is one of several hormones essential for life. The absence of cortisol leads to the body’s inability to maintain homeostasis, particularly when confronted with a stress such as infection, which is usually fatal within days without cortisol.

• Primary Adrenal Insufficiency: Also known as Addison’s Disease. Results from autoimmune attack.

• Figure 11.26: Patient with florid Cushing’s syndrome.

11.16 Other Hormones Released During Stress

• Other hormones that are usually released during many kinds of stress are aldosterone, vasopressin, growth hormone, glucagon, and beta-endorphin.

• Table 11.3: Actions of the sympathetic nervous system, including epinephrine secreted by the adrenal medulla, during stress

11.17 Bone Growth

• One of the major functions of the endocrine system is to control growth.

• Figure 11.27A growing long bone is divided, for descriptive purposes, into the ends, or epiphyses, and the remainder, the shaft.

• Figure 11.28 Relative growth in brain, total-body height, and reproductive organs.

11.18 Environmental Factors Influencing Growth

• Adequate nutrition and good health are the primary environmental factors influencing growth.

11.19 Hormonal Influences on Growth

• Table 11. 4 Major Effects of Growth Hormone

• Figure 11.29: Hormonal pathways controlling the secretion of growth hormone and insulin-like growth factor-1.

• Table 11. 5 Major Hormones Influencing Growth Hormone. GH Principal Actions Growth hormone Main controller of postnatal growth stimulates cellular uptake amino acids and protein. Inhibits protein breakdown. Insulin is required also

11.20 Effector Sites for Ca2+ Homeostasis

• Bone is a connective tissue made up of several cell types surrounded by a collagen matrix called osteoid, upon which are deposited minerals, particularly the crystals of calcium, phosphate, and hydroxyl ions known as hydroxyapatite.

• Figure 11.30 The three types of bone cells involved in bone formation and breakdown are osteoblasts, osteocytes, and osteoclasts.

11.21 Hormonal Controls

• Figure 11.31 The parathyroid glands and thyroid gland.

• Figure 11.32 PTH increases calcium concentrations in bones.

• Parathyroid hormone and 1,25-(OH)2D are also involved in the control of phosphate ion concentrations.

• Figure 11.33 Metabolism of vitamin D to the active form, 1,25-(OH)2D.

11.22 Metabolic Bone Diseases

• Osteomalacia (adults) and rickets (children): deficient bone mineralization caused by inadequate vitamin D intake, absorption, or activation

Endocrine System Case Study

• The case for acromegaly. Figure 11.34 A individual with gigantism and acromegaly Acromegaly and gigantism arise when chronic, excess amounts of growth hormone are secreted into the blood.
  Figure 11.35 A growth hormone–secreting tumor causes features of acromegaly and gigantism by direct GH effects and by GH-induced increases in IGF-1.

11.7 Types of Endocrine Disorders

• Features vary based on the hormone affected, but all endocrine diseases can be categorized in one of four ways:

  • Too little hormone (hyposecretion).

  • Too much hormone (hypersecretion).

  • Target-cell hyporesponsiveness.

  • Target-cell hyperresponsiveness.

• Hyposecretion:

  • Primary hyposecretion:

    • Gland not functioning normally.

  • Secondary hyposecretion:

    • Gland is not damaged (at least at first) but is receiving too little stimulation by its tropic hormone.

• Hypersecretion:

  • Primary hypersecretion (the gland is secreting too much of the hormone on its own).

  • Secondary hypersecretion (excessive stimulation of the gland by its tropic hormone).

• Hyporesponsiveness and Hyperresponsiveness

  • The target cells do not respond normally to the hormone: Hyporesponsiveness or hormone resistance.

  • Hyperresponsiveness can also occur and cause problems.

11.8 Control Systems Involving the Hypothalamus and Pituitary Gland

• The pituitary gland (hypophysis) lies in the sella turcica at the brain's base, connected to the hypothalamus by the infundibulum (pituitary stalk).

• The pituitary gland consists of the anterior pituitary gland (adenohypophysis) and the posterior pituitary gland (neurohypophysis).

• Figure 11.14 shows the relationship of the pituitary gland to the brain and hypothalamus and neural and vascular connections between the hypothalamus and pituitary gland.

• Posterior Pituitary Hormones

  • The posterior pituitary is a neural extension of the hypothalamus.

  • Hormones are synthesized in the supraoptic and paraventricular nuclei and transported down axons to the posterior pituitary.

  • Two hormones (oxytocin and vasopressin) are released from axon terminals directly into capillaries.

  • Oxytocin:

    • Stimulates contraction of smooth muscle cells in the breasts, which results in milk ejection during lactation.

    • Stimulates contraction of uterine smooth muscle cells, until eventually the fetus is delivered.

  • Vasopressin:

    • Acts on smooth muscle cells around blood vessels to cause their contraction, which constricts the blood vessels and thereby increases blood pressure.

    • Acts within the kidneys to decrease water excretion in the urine: antidiuretic hormone (ADH).

• Anterior Pituitary Gland Hormones and the Hypothalamus

  • Other nuclei of hypothalamic neurons secrete hormones that control the secretion of all the anterior pituitary gland hormones: hypophysiotropic hormones.

  • With one exception (dopamine), each of the hypophysiotropic hormones is the first in a three-hormone sequence (Figure 11.15).

  • Overview of Anterior Pituitary Gland Hormones

    • 6 hormones:

      • Follicle-stimulating hormone (FSH)

      • Luteinizing hormone (LH)

      • Growth hormone (GH, also known as somatotropin)

      • Thyroid-stimulating hormone (TSH, also known as thyrotropin)

      • Prolactin

      • Adrenocorticotropic hormone (ACTH, also known as corticotropin)

  • Figure 11.16 summarizes the target organs and major functions of the six classical anterior pituitary gland hormones.

    • Thyroid-stimulating hormone induces the thyroid to secrete thyroxine and triiodothyronine.

    • Adrenocorticotropic hormone stimulates the adrenal cortex to secrete cortisol.

    • Growth hormone stimulates the liver to secrete a growth-promoting peptide hormone known as insulin-like growth factor-1 (IGF-1) and, in addition, exerts direct effects on bone and on metabolism.

    • Follicle-stimulating hormone and luteinizing hormone stimulate the gonads to secrete the sex hormones.

    • Prolactin has a major function to stimulate development of the mammary glands during pregnancy and milk production.

  • Hypophysiotropic Hormones

    • Anterior pituitary gland hormones regulated by hormones produced by the hypothalamus, collectively called hypophysiotropic hormones.

    • Secreted by neurons that originate in discrete nuclei of the hypothalamus and terminate in the median eminence (Figure 11.17).

    • Hormone secretion by the anterior pituitary gland is controlled by hypophysiotropic hormones released by hypothalamic neurons that are transported to the anterior pituitary gland by way of the hypothalamo–hypophyseal portal vessels.

    • When an anterior pituitary gland hormone is secreted, it will diffuse into the same capillaries that delivered the hypophysiotropic hormone.

    • The portal circulatory system ensures that hypophysiotropic hormones can reach the cells of the anterior pituitary gland at a high concentration and with very little delay.

    • Two crucial differences, however, distinguish two systems.

      • First, the axons of the hypothalamic neurons that secrete the posterior pituitary hormones leave the hypothalamus and end in the posterior pituitary, whereas those that secrete the hypophysiotropic hormones are much shorter and remain in the hypothalamus, ending on capillaries in the median eminence.

      • Second, most of the capillaries into which the posterior pituitary hormones are secreted immediately drain into the general circulation, which carries the hormones to the heart for distribution to the entire body. In contrast, the hypophysiotropic hormones enter capillaries in the median eminence of the hypothalamus that do not directly join the main bloodstream but empty into the hypothalamo–hypophyseal portal vessels, which carry them to the cells of the anterior pituitary gland.

      • Figure 11.18: Hypophysiotropic hormones impact on the anterior pituitary gland.

        • Secretion of ACTH (corticotropin) is stimulated by corticotropin-releasing hormone (CRH).

        • Secretion of growth hormone is stimulated by growth hormone–releasing hormone (GHRH).

        • Secretion of thyroid-stimulating hormone (thyrotropin) is stimulated by thyrotropin-releasing hormone (TRH).

        • Secretion of both luteinizing hormone and follicle-stimulating hormone (the gonadotropins) is stimulated by gonadotropin-releasing hormone (GnRH).

          • Somatostatin (SST) inhibits the secretion of growth hormone.

        • Dopamine (DA) inhibits the secretion of prolactin.

    • Figure 11.19 summarizes the hypothalamic–anterior pituitary gland system.

  • Neural Control of Hypophysiotropic Hormones

    • Neurons of the hypothalamus receive stimulatory and inhibitory synaptic input from virtually all areas of the central nervous system.

    • The neural inputs to these cells arise from other regions of the hypothalamus, which in turn are linked to inputs from visual pathways that recognize the presence or absence of light.

    • There is a strong circadian influence over the secretion of certain hypophysiotropic hormones.

  • Hormonal Feedback Control of the Hypothalamus and Anterior Pituitary Gland

    • A prominent feature of each of the hormonal sequences initiated by a hypophysiotropic hormone is negative feedback exerted upon the hypothalamo–hypophyseal system by one or more of the hormones in its sequence.

    • The situation described for cortisol, in which the hormone secreted by the third endocrine gland in a sequence exerts a negative feedback effect over the anterior pituitary gland and/or hypothalamus, is known as a long-loop negative feedback (Figure 11.20).

    • The influence of an anterior pituitary gland hormone on the hypothalamus is known as a short-loop negative feedback (see Figure 11.20).

  • The Role of “Nonsequence” Hormones on the Hypothalamus and Anterior Pituitary Gland

    • There are many stimulatory and inhibitory hormonal influences on the hypothalamus and/or anterior pituitary gland other than those that fit the feedback patterns just described.

11.9 Synthesis of Thyroid Hormone

• The thyroid gland produces two iodine-containing molecules of physiological importance, thyroxine (called T4 because it contains four iodines) and triiodothyronine (T3, three iodines; review Figure 11.3).

• A considerable about of T4 is converted to T3 in target tissues by enzymes known as deiodinases.

• Figure 11.21: Location of the bilobed thyroid gland.

• Figure 11.22: Steps involved in T3 and T4 formation.

11.10 Control of Thyroid Function

• The basic control mechanism of TSH production is the negative feedback action of T3 and T4 on the anterior pituitary gland and, to a lesser extent, the hypothalamus (Figure 11.23).

• Figure 11.23: TRH-TSH-thyroid hormone sequence.

• TSH also increases protein synthesis in follicular epithelial cells, increases DNA replication and cell division, and increases the amount of rough endoplasmic reticulum and other cellular machinery required by follicular epithelial cells for protein synthesis.

• An enlarged thyroid gland from any cause is called a goiter.

11.11 Actions of Thyroid Hormone

• Receptors for thyroid hormone are present in the nuclei of most of the cells of the body, unlike receptors for many other hormones, whose distribution is more limited.

• Like steroid hormones, T3 acts by inducing gene transcription and protein synthesis.

• Metabolic Actions:

  • T3 stimulates carbohydrate absorption from the small intestine and increases fatty acid release from adipocytes.

  • Permissive Actions:

    • Some of the actions of T3 are attributable to its permissive effects on the actions of catecholamines.

  • Growth and Development

    • T3 is required for normal production of growth hormone from the anterior pituitary gland. Therefore, when T3 is very low, growth in children is decreased.

11.12 Hypothyroidism and Hyperthyroidism

• Any condition characterized by plasma concentrations of thyroid hormones that are chronically below normal is known as hypothyroidism.

• The most common cause of hypothyroidism in the United States is autoimmune disruption of the normal function of the thyroid gland, a condition known as autoimmune thyroiditis.

• Figure 11.24: Goiter at an advanced stage.

• In severe, untreated hypothyroidism:

  • certain hydrophilic polymers are present.

  • certain hydrophilic polymers:<

    As in the case of hypothyroidism, there are a variety of ways in which hyperthyroidism, or thyrotoxicosis, can develop.

11.13 Physiological Functions of Cortisol

• A real or perceived threat to homeostasis.

• Invariably, the secretion from the adrenal cortex of the glucocorticoid hormone cortisol is increased.

• Figure 11.25 is the CRH-ACTH-cortisol pathway.

11.14 Functions of Cortisol in Stress

• Table 11.2 summarizes that the major effects of increased plasma concentration of cortisol during stress influence organic metabolism, enhance vascular reactivity, have protective effects against damaging influences of stress, inhibit inflammation and specific immune responses, and inhibit nonessential functions.

11.15 Adrenal Insufficiency and Cushing’s Syndrome

• Cortisol is one of several hormones essential for life. The absence of cortisol leads to the body’s inability to maintain homeostasis, particularly when confronted with a stress such as infection, which is usually fatal within days without cortisol.

• Primary Adrenal Insufficiency: Also known as Addison’s Disease. Results from autoimmune attack.

• Figure 11.26: Patient with florid Cushing’s syndrome.

11.16 Other Hormones Released During Stress

• Other hormones that are usually released during many kinds of stress are aldosterone, vasopressin, growth hormone, glucagon, and beta-endorphin.

• Table 11.3: Actions of the sympathetic nervous system, including epinephrine secreted by the adrenal medulla, during stress

11.17 Bone Growth

• One of the major functions of the endocrine system is to control growth.

• Figure 11.27A growing long bone is divided, for descriptive purposes, into the ends, or epiphyses, and the remainder, the shaft.

• Figure 11.28 Relative growth in brain, total-body height, and reproductive organs.

11.18 Environmental Factors Influencing Growth

• Adequate nutrition and good health are the primary environmental factors influencing growth.

11.19 Hormonal Influences on Growth

• Table 11. 4 Major Effects of Growth Hormone

• Figure 11.29: Hormonal pathways controlling the secretion of growth hormone and insulin-like growth factor-1.

• Table 11. 5 Major Hormones Influencing Growth Hormone. GH Principal Actions Growth hormone Main controller of postnatal growth stimulates cellular uptake amino acids and protein. Inhibits protein breakdown. Insulin is required also

11.20 Effector Sites for Ca2+ Homeostasis

• Bone is a connective tissue made up of several cell types surrounded by a collagen matrix called osteoid, upon which are deposited minerals, particularly the crystals of calcium, phosphate, and hydroxyl ions known as hydroxyapatite.

• Figure 11.30 The three types of bone cells involved in bone formation and breakdown are osteoblasts, osteocytes, and osteoclasts.

11.21 Hormonal Controls

• Figure 11.31 The parathyroid glands and thyroid gland.

• Figure 11.32 PTH increases calcium concentrations in bones.

• Parathyroid hormone and 1,25-(OH)2D are also involved in the control of phosphate ion concentrations.

• Figure 11.33 Metabolism of vitamin D to the active form, 1,25-(OH)2D.

11.22 Metabolic Bone Diseases

• Osteomalacia (adults) and rickets (children): deficient bone mineralization caused by inadequate vitamin D intake, absorption, or activation

Endocrine System Case Study

• The case for acromegaly. Figure 11.34 A individual with gigantism and acromegaly Acromegaly and gigantism arise when chronic, excess amounts of growth hormone are secreted into the blood.<

  Figure 11.35 A growth hormone–secreting tumor causes features of acromegaly and gigantism by direct GH effects and by GH-induced increases in IGF-1.