Chapter 11 The Neurotransmitter from a nerve cell

Nerve cell

Nerve signals

Neurotransmitter molecules

Nerve cell / muscle cell / gland cell from an endocrine cell are chemical messengers that enter the blood, which carries them from their site of secretion to the cells upon which they act. The endocrine system consists of all those glands, called endocrine glands, that secrete hormones. Secretory vesicles Endocrine cell

Hormone molecules

Blood vessel

Target cell Exocrine gland vs.

Hormone-secreting cells Comparison between nervous system and endocrine system Types of hormones (1) (1) and proteins (2) Amines (3) Steroids

Thyroid hormones Types of hormones (2) Chemical structures of the amine hormones

Thyroid hormones By thyroid gland

Ps. make steroid hormones

By adrenal medulla

Catecholamines

Phenyl-N-methyl transferase (PNMT) (1X) Epinephrine (4X)

By Typical synthesis and secretion of hormones

Most hormones

@ ribosome @ Golgi

@ rER Structures of representative steroid hormones and their structure relationship to cholesterol

Adrenal cortex (testes, )

1,25-dihydroxyvitamin D (from the kidneys) Steroid synthesis

cytochrome P450s The major five hormones secreted from the adrenal cortex

Androgens (-like hormones)

DHEA

(1) Organic metabolism (2) Responses to stress (3) Regulation of the immune system

(1) Na+ and H O retension Mineralocorticoid 2 (2) K+ and H+ excretion in the urine

IP3 Angiotensin II Section through and Corticosterone Masculinization

(1) Excessive body & facial hairs

(2) Muscle development

(3) Deepend voice Gonadal production of steroids

Only the ovaries have high concentration of the enzyme

Categories of hormones

A hormone’s concentration in the plasma depends upon (1) its rate of secretion by the endocrine glans (2) its rate of removal from the blood Human endocrine glands and some of their hormones (1) Human endocrine glands and some of their hormones (2) Possible fates and actions of a hormone following it secretion by an endocrine cell The ability of thyroid hormone to “permit” epinephrine-induced release of fatty acids from cells Permissiveness: hormone A must be present for the full strength of hormone B’s effect.

By causing an increased number of epinephrine receptors (-adrenergic receptors) Input that act directly on endocrine gland cells to stimulate or inhibit hormone secretion

Ex: paracrine Example of how the direct control of hormone secretion by the plasma concentration of a substance Pathways by which the nervous influences hormone secretion Types of endocrine disorders

(1) Too little hormone: hyposecretion

(2) Too much hormone: hypersecretion

(3) Reduced responsiveness of the target cells to hormone (hyporesponsiveness)

(4) Increased responsiveness of the target cells to hormone (hyperresponsiveness) Hyposecretion

Primary hyposecretion: an endocrine gland may be secreting too little hormone because the gland cannot function normally. (1) Partial destruction of a gland; (2) An enzyme deficiency resulting in decreased synthesis of the hormone; (3) Dietary deficiency of iodine (thyroid hormones)

Secondary hyposecretion: the endocrine gland is not damaged initially but is receiving too little of its tropic hormone.

If tropic hormone : primary Dwarfish: If tropic hormone : secondary hyposecretion of

Treatment: to administer the missing hormone or a synthetic analog of the hormone. Hypersecretion Acromegaly: Primary hypersecretion: hypersecretion of growth hormone the gland is secreting too much of the hormone on it own.

Secondary hypersecretion: excessive stimulation of the gland by its tropic hormone.

If tropic hormone  & target hormone : primary If tropic hormone & target hormone : secondary

Treatment: surgery Radiation Drugs that inhibit a hormone’s synthesis Drugs that block the hormone’s action on its target cells Hyporesponsiveness & Hyperresponsiveness

Hyporesponsiveness: the target cells do not respond normally to the hormone.

(1) Deficiency of receptors-or abnormal receptors-for the hormone.

(2) The receptors for a hormone may be normal but some event that occurs after hormone binds to receptors may be defective. (ex: cAMP)

(3) Require metabolic activation by some other tissue after secretion. There may be a deficiency of the enzymes that catalyze the activation. (ex: testosterone →→→ dihydrotestosterone)

Hyperresponsiveness: Thyroid hormone causes an up-regulation of certain receptors for epinephrine; therefore, hypersecretion of thyroid hormone causes a hyperresponsiveness to epinephrine. (increased rate with elevated levels of thyroid hormones) Type 2 diabetes

 Type 2 (non--dependent) is - caused by a reduced response to insulin. - associated with being overweight and underactive. - the cause of more than 90% of diabetes. Location of the hypothalamus and pituitary

Brain

Hypothalamus

Posterior pituitary

Anterior pituitary

Bone Hormone of the Hypothalamus

Neurosecretory Hormone cell

Posterior pituitary

Anterior Blood pituitary vessel

ADH: antidiuretic hormone ADH

Uterine muscles Mammary glands tubules Hormone of the Neurosecretory cell of hypothalamus

releasing hormones inhibiting hormones Blood vessel Releasing hormones TSH: thyroid-stimulating hormone from hypothalamus ACTH: adrenocorticotropic hormone

Endocrine cells of FSH: follicle-stimulating hormone the anterior pituitary LH:

Pituitary hormones PRL:

GH: Growth hormone TSH ACTH FSH Prolactin Growth and (PRL) hormone Endophines LH (GH)

Thyroid Adrenal Testes or Mammary Entire Pain cortex ovaries glands body receptors (in mammals) in the brain Neural and vascular connections between the hypothalamus and pituitary gland Hormone secretion by the anterior pituitary gland The effect of definitely established hypophysiotropic hormones

Hypophysiotropic hormones = hypothalamic releasing or inhibiting hormones

?

peptides catecholamine Targets and major functions of the six classical anterior pituitary gland hormone

Growth hormone Thyroid-stimulating Adrenocorticotropic Gonadotropic hormones somatotropin hormone hormone gonadotropins thyrotropin corticotropin

Follicle-stimulating Luteinizing hormones hormone

T4

T3

- →→ mobilize fats in the circulation -endrophin →→ pain-killing The hypothalamic-anterior pituitary gland system Typical sequential pattern by which a hypophysiotropic hormone controls the secretion of downstream hormones CRH-ACTH- sequence

Stressful stimuli Nonstress inputs Short-loop and long-loop feedbacks Colloid in the bilobed thyroid gland

Thyroxine (T4)  deiodinases  Protein-rich Triiodothyronine (T3)

Receptors for thyroid hormones are present in the nuclei of most of the cells of the body, but have a much higher affinity for T3. Steps involved in T3 and T4 formation

Iodide trapping

Thyroid peroxidase

DIT: diiodotyrosine MIT: monoiodotyrosine

Thyroid peroxidase

T3, T4 stimulate the activity of Na+/K+-ATPase

(1) Stimulate carbohydrate absorption from the small intestine (2) Increase fatty acid release from adipocytes  Provide energy to maintain metabolic rate at a high level (calorigenic action  heat production) TRH-TSH-thyroid hormone sequence Permissive actions of thyroid hormones

T3, T4 

-adrenergic receptors 

Epinephrine & Norepinephrine mediated sympathetic nervous system activity  Hypothyroidism

Hypothyroidism: the plasma levels of T3 and T4 are chronically below normal. Most cases of hypothyroidism (95%) are primary defects resulting from damage to or loss of functional tissue or from inadequate iodine consumption.

The signs and symptoms of hypothyroidism: (1) An increased sensitivity to cold (cold intolerance) and a tendency toward weight gain. (2) In severe, certain hydrophilic polymers called glycosaminoglycans accumulate in the interstitial space in scattered regions of the body.  Myxedema Goiter at an advanced stage

If a thyroid cell is exposed to higher TSH levels than normal, it will undergo hypertrophy (increase in size). An enlarged thyroid gland from any cause is called goiter. Cretinism (congenital hypothyroidism)

T3 and T4 are among the most important developmental hormones for the nervous system. (1) Formation of axon terminals. (2) Production of synapses. (3) Growth of dendrites. (4) Formation of myelin.

Dwarfism Cretinism I. Hypopituitarism Hypothyroidism II.  GH  T4, T3 III. Short stature, smart look Short stature, ugly look Proportionate body parts Disproportionately small body parts IV. Mentally normal Mentally retarded (IQ normal) (low IQ) V. Sexual infantilism Sexual infantilism small gonads Autoimmune thyroiditis

Autoimmune thyroiditis is autoimmune disruption of the normal function of the thyroid gland.

Hashimoto’s disease, in which cells of the immune system called T cells attack and destroy thyroid tissue. Hashimoto’s disease is more common in women and can slowly progress with age.

Sex and the City's Kim Cattrall has Hashimoto's disease Dr Hakaru Hashimoto Hyperthyroidism (thyrotoxicosis)

(1) Hormone-secreting tumors of the thyroid (rare)

(2) An autoimmune disease called Grave’s disease (most common) Overstimulation of the growth and activity of the thyroid gland. Hyperthyroid patients tend to have heat intolerance.

(1) Treated with drugs that inhibit thyroid hormone synthesis.

(2) Surgical removal of the thyroid gland.

(3) Destroying a portion of the thyroid using radioactive iodine. Hormonal pathways controlling the secretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1)

Growth hormone-releasing hormone Somatastatin

Growth hormone

Insulin-like growth factor-1 Major effects of growth hormone Major hormones influencing growth Anatomy of a long bone during growth

(a plate of actively proliferating cartilage)

Osteoblasts  Chondrocytes  New cartilage Relative growth in brain, total-body height, and reproductive organs

(long-bone and vertebral growth) Excessive production of growth hormone Acromegaly Gigantism (in adult) (in childhood) Pituitary dwarfish Appearance of a man with gigantism and acromegaly

I ate Effect sites for Ca2+ homeostasis Ca2+ homeostasis depends on an interplay among bone, the kidneys, and the gastrointestinal tract. Cross section through a small portion of bone

(bone-resorbing cells) (bone-forming cells)

Mineralized osteoid Summary of major hormone influences on bone mass

The two major hormones that regulate plasma Ca2+ concentration are and 1,25-dihydroxyvitamin D. A third hormone, , plays a limited role.

(1) Hormones that favor bone formation and increased bone mass Insulin Growth hormone Insulin-like growth factor 1 (IGF-1) Testosterone Calcitonin

(2) Hormones that favor increased bone resorption and decreased bone mass Parathyroid hormone (chronic elevations) Cortisol

Thyroid hormones (T4 and T3) The parathyroid glands Parathyroid hormone production is controlled by the extracellular Ca2+ concentration acting directly on the secretory cells via plasma membrane Ca2+ receptor.

Ca2+ PTH  Ca2+ PTH  Mechanisms that allow parathyroid hormone to reverse a reduction in plasma Ca2+ concentration toward normal

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

(a protein hormone)

Directly: bone, kidneys Indirectly: intestine

P3+ 

P3+  P3+ 

P3+  Metabolism of vitamin D to the active form, 1,25-(OH)2D

= (an ) Calcitonin Calcitonin is a peptide hormone secreted by cells called thyroid parafollicular cells.

Calcitonin decreases plasma Ca2+ concentration, mainly by inhibiting osteoclasts, thereby reducing bone resorption.

Its secretion is stimulated by an increased plasma Ca2+ concentration.

- + Metabolic bone diseases (1)

Mineralization of bone matrix is deficient, causing the bones to be soft and easily fractured. A major cause of rickets and osteomalacia is deficiency of vitamin D.

Rickets (in children) Osteomalacia (in adults) Metabolic bone diseases (2) In osteoporosis, both matrix and minerals are lost as a result of an imbalance between bone resorption and bone formation. The resulting decrease in bone mass and strength leads to an increased incidence of fractures.

Interleukin-1  bone loss

(1) or its synthetic analogs in postmenopausal women. (2) A regular weight-bearing exercise program. (3) Adequate dietary Ca2+ (1000 to 1500 mg/day) and vitamine D intake (4) Bisphosphonates: interfere with the resorption of bone by osteoclasts) Selective estrogen receptor modulators (SERMs): act by interacting with estrogen receptors Hypercalcemia

(1) Primary hyperparathyroidism: caused by a benign tumor (adenoma) of one of the four parathyroid glands.

Primary hyperparathyroidism is most effectively treated by surgical removal of the parathyroid tumor.

(2) Humoral hypercalcemia of malignancy: release of a molecule that is chemically similar to PTH by certain types of cancer, called PTH-related peptide (PTHrp), and that has effects similar to those of PTH.

(3) Excessive ingestion of vitamin D Hypocalcemia

(1) Primary hypoparathyroidism: result from a loss of function.

(2) Pseudohypoparathyroidism: resistance to the effect of PTH in target tissue..

(3) Secondary hypoparathyroidism: failure to absorb vitamin D from the gastrointestinal tract, or decreased

kidney 1,25-(OH)2D production.

Increase the excitability of nerves and muscles: a. CNS effects (seizures) b. Muscle spasms (hypocalcemic tetany) c. Neuronal excitability Effects of increased plasma cortisol concentration during stress Cushing’s syndrome Excess cortisol in the blood. Actions of the sympathetic nervous system, including epinephrine secreted by the adrenal medulla, during stress

1. Increased hepatic and muscle glycogenolysis (provides a quick source of glucose).

2. Increased breakdown of adipose tissue triglyceride (provides a supply of glycerol for gluconeogenesis and of fatty acids for oxidation).

3. Increased cardiac function (e.g,.increased heart rate).

4. Diversion of blood from viscera to skeletal muscles by means of vasoconstriction in the former beds and vasodilation in the latter.

5. Increased lung ventilation by stimulating brain breathing centers and dilating airways,