Endocrine tissues are ___

Diverse and decentralized

Hypothalamus

Inhibitory hormones

Pituitary gland

Systemic hormones

Pineal gland

Melatonin

Adipose

Leptin

Heart

Atrial natriuretic factor

Liver

Erythropoietin, IGF

Adrenal glands

Steroids, catcholamine

Ovaries

Estrogen, inhibin

Testes

Testosterone, inhibin

Intestine

Secretin

Kidneys

Calcitriol, angiotensin II

Pancreas

Insulin, glucagon

Stomach

Gastrin

Thyroid gland

- Thyroxine (T4)

- Triiodothyronine (T3)

- Calcitonin

Parathyroid glands

Parathyroid hormone (PTH)

Hypothalamus is considered ___

Neuroendocrine

Anterior pituitary

- Thyroid stimulating hormone

- Adrenocorticotropic hormone

- Luteinizing hormone

- Follicle stimulating hormone

- Growth hormone

- Prolactin

Posterior pituitary

- Antidiuretic hormone

- Oxytocin

Adrenal cortex

- Mineralocorticoids (aldosterone)

- Glucocorticoids (cortisol)

- Gonadocorticoids

Adrenal medulla

Epinephrine and norepinephrine (catecholamines)

Thymus

- Thymosin

- Thymopoietin

Endocrine cell

Releases chemical messengers (hormones) into the bloodstream

- Only cells with receptors for that particular hormone will respond

Hormones

Long-distance chemical messengers, traveling in the blood or lymph to bind to receptors on their target organs

Tropic hormones

Hormones which target organ is another endocrine gland, affecting its activity

Autocrine

Chemical messengers that exerts effects on the same cells that secrete them (not considered endocrine)

Paracrine

Chemical messengers that affect neighboring cells (not considered endocrine)

Amino acid-based hormones

Amino acid derivatives, peptides, and proteins

Steroids

Synthesized from cholesterol and gonadal and adrenocortical hormones

Steroids

- Lipophilic

- Plasma, cytosolic, and nuclear receptors

- Endocrine

- Ex: estrogen

Peptides (1)

- Lipophilic

- Cytosolic and nuclear receptors

- Endocrine

- Ex: thyroxine

Peptides (2)

- Hydrophilic

- Plasma receptors

- Endocrine

- Ex: adrenocorticotropic hormone

Proteins

- Hydrophilic

- Plasma receptors

- Endocrine

- Ex: growth hormone

Purinergic

- Hydrophilic

- Plasma receptors

- Paracrine

- Ex: ATP

Prostaglandins

- Lipophilic

- Plasma receptors

- Endocrine like

- Ex: prostaglandin f2a

Gases

- Lipophilic

- Cytosolic receptors

- Paracrine

- Ex: nitric oxide

Neurotransmitters

- Hydrophilic

- Plasma receptors

- Paracrine

- Ex: acetylcholine

Properties of hormones

- Regulation of physiological processes

- Variety in chemical structure

- Released in low quantities

- Movement through diffusion or plasma

- Bind to receptors on target cells

- Released in response to changes in homeostasis

Hormones regulate the ___ ___ of other hormones

Receptor levels

Upregulation

Increasing receptor levels on target cells

Downregulation

Decreasing receptor levels on target cells

Permissiveness

The process of hormones regulating the receptor levels of other hormones

Hormone release is ___ ___

Amplitude-modulated

Neurotransmitters

- Release in "all or nothing"

- Vary in frequency

Hormones

- Levels never approach zero

- Fluctuate between high and low

Peptide and protein hormones are synthesized in an ___ ___

Inactive form

Peptide and protein hormones

- Encoded by genes

- Multiple peptide hormones can be encoded by one gene

- Signal peptide: directs hormone to correct intracellular organelle for processing

Synthesis of amino acid derivative hormones

- Biochemically synthesized from amino acids

- Store within vesicles

- Ex: epinephrine

Processes that influence hormone secretion

- Changes in a critical physiological factor (ex: ions)

- Direct input from the nervous system through neurohormone release

- Actions of other hormones (ex: hypothalamic regulation of pituitary gland)

- Mechanical stresses or cellular metabolism

Hormones are ___ through the blood

Transported

Fat/lipid-soluble hormone

- >99% bound to transport protein, <1% free

- Some excreted in urine (if chemically modified to be more water-soluble)

- Otherwise excreted in GI tract

Water-soluble hormone

- 100% free

- Smaller than kidney filtration barrier

- Excreted in urine

Half life

Time required to reduce blood concentration of a hormone by 50%

Increases half life

- Increased synthesis

- Increased secretion

- Binding to transport proteins

- Modification of structure

Decreases half life

- Decreased synthesis

- Decreased secretion

- Excretion by kidney or bile

- Enzymatic degradation, addition of a side chain, or reabsorption by the kidney

___ can change hormone levels or activity

Metabolism

Hormones act in one of two ways

1. based on their chemical structure

2. based on their receptor location (integral protein on plasma membrane vs. intracellular receptor)

Water-soluble hormones (hydrophilic)

all amino acid-based hormones, except thyroid hormone

Act on integral protein receptors on plasma membrane or via second-messenger systems, since they are not able to enter the cell

Lipid-soluble hormones (hydrophobic)

all steroid (cholesterol) and thyroid hormones

Act on intracellular receptors that can directly activate enzymes or regulatory sequences on DNA, as they can enter the cell

Water-soluble hormones (hydrophilic)

1. Integral plasma membrane receptor

2. Second-messenger system

Integral plasma membrane receptor

Receptor embedded on plasma membrane

Second-messenger system

- Receptors on plasma membrane exert effects of hormone binding by activating a 2nd intracellular messenger

- cAMP (cyclic adenosine monophosphate)

- PIP2- calcium (phosphatidyl inositol bisphosphate calcium)

G-protein coupled receptors (GPCRs)

- Integral membrane proteins

- Extracellular region binds hormone

- Intracellular region interacts with G-proteins

Subunits of G-proteins

- Gas

- Gai

- Gaq

Gas

- Activates adenylate cyclase (AC)

- Converts ATP to cAMP

Gai

- Inhibits adenylate cyclase (AC)
- Blocks production of cAMP

Gaq

Activates phospholipase C (PLC)

- Breaks down PIP2 into IP3 and DAG

Effects of cAMP

- Activates protein kinase A (PKA)

- Degraded by phosphodiesterase (PDE)

Effects of DAG and IP3

- IP3 causes Ca2+ release from ER

- DAG activates protein kinase C (PKC)

One-transmembrane spanning receptors (1-TMS)

- Integral membrane proteins

- Extracellular region binds hormone

- Intracellular region contains a kinase domain; directly activates enzymes without G-proteins

Nuclear receptors

- Found inside the cell

- Act as transcription factors

- Generally cytoplasmic proteins complexed with heat shock proteins (HSPs)

- Hormone binding leads to dissociation of HSPs, dimerization to a second bound receptor, and translocation to the nucleus

Thyroid stimulating hormone receptor causes

Grave's disease (hyperthyroidism)

Parathyroid hormone receptor causes

Jansen's metaphyseal chondrodysplasia

Follicle-stimulating hormone receptor causes

Ovarian dysgenesis type I

Melanocortin/adrenocorticotropic hormone receptor causes

Familial glucocorticoid definciency

Luteinizing hormone receptor causes

Familial male precocious puberty

Antidiuretic hormone receptor causes

Familial hypocalciuric hypercalcemia

Gonadotropin-releasing hormone receptor

Hypogonadotropic hypogonadism

Anatomy of the hypothalamus

- Located inferior to the thalamus; part of the limbic system

- Contains many distinct nuclei that produce and release unique hormones

- Is sexually dimorphic (different between men and women)

- Hypophyseal portal system connects hypothalamus and anterior pituitary via two capillary beds in series

Hypothalamus releases hormones that act on ___ ___

Pituitary gland

Thyrotropin releasing hormone (TRH)

(hypothalamic hormone)

Effect at anterior pituitary: TSH and prolactin release

Corticotropin releasing hormone (CRH)

(hypothalamic hormone)

Effect at anterior pituitary: ACTH release

Growth hormone releasing hormone (GHRH)

(hypothalamic hormone)

Effect at pituitary: GH release

Gonadotropin releasing hormone (GnRH)

(hypothalamic hormone)

Effect at pituitary: FSH and LH release

Prolactin inhibitory hormone (PIH or dopamine)

Effect at pituitary: inhibition of prolactin release

Growth hormone inhibitory hormone (GIRH, somatostatin)

Effect at pituitary: inhibition of GH and TSH release

Anatomy of the pituitary gland

- Located inferior to the hypothalamus

- Composed of anterior, intermediate and posterior lobes

- Anterior lobe: subdivided into pars tuberalis and pars distalis

- Two pituitary areas do not regulate each other

Hormones secreted by the posterior pituitary gland

- Oxytocin

- Antidiuretic hormone

Oxytocin

- Movement of mammary milk into subaereolar sinuses (milk ejection/letdown)

- Stimulation of uterine contraction during pregnancy

- Social behavior: feelings of contentment, reduced anxiety, calmness

Antidiuretic hormone

- Renal system: increased expression of aquaporin channels (increased water absorption); increased interstitial osmolarity (increased water, Na+ reabsorption)

- Cardiovascular system: vasoconstriction

- CNS: aggression, blood pressure, body temperature regulation

Types of pituitary adenoma

- Benign (65% of the time)

- Invasive (0.1%)

- Carcinoma (35%)

Symptoms of pituitary adenoma

- Over-secretion of one or two hormones

- Eye disorders (compression of optic nerve)

- Severe headaches

- Under-secretion of some hormones

Anatomy of the thyroid gland

- Found lateral to the upper trachea

- Made up of two lobes connected by highly vascularized band of tissues called isthmus

- Contains follicles that store thyroglobulin, the substrate for thyroxine

- Parafollicular cells are scattered between follicles and secrete calcitonin

Effects of thyroxine throughout the body

- Cold, nutrient status

- Increased lung ventilation

- Increased metabolic rate (liver)

- Increased lipolysis in adipose tissue

- Increased protein catabolism in muscle

- Increased heart rate, force contraction, cardiac output

Thyroxine synthesis in the thyroid gland

1. Iodide ions transported into follicular cells

2. TSH stimulates TG synthesis and storage within follicles

3. Iodide is oxidized to iodine by thyroid peroxidase; diffuses to follicle lumen

4. Iodine atoms are covalently attached to tyrosine residues on thyroglobulin, forming MIT or DIT

5. Two DIT molecules join to form T4, or one MIT and one DIT join to form T3

6. Follicular cells take up iodinated thyroglobulin by endocytosis. Within endosomes, proteolytic enzymes release thyroxine from TG

7. Thyroxine is released into blood bound to proteins (ex: TBG or albumin)

Anatomy of the parathyroid gland

- Four parathyroid glands (2 embedded in each thyroid gland)

- Densely-packed with chief and oxyphil cells

- Mainly secrete parathyroid hormone (PTH)

Effects of parathyroid hormone throughout the body

- Bone: increased resorption

- Kidney: increased calcitriol

- Intestine: increased calcium reabsorption

Anatomy of the adrenal glands

- Embedded in adipose tissue in the superior regions of the kidney

- Composed of endocrine and nervous tissue

- Organized into zones which are structurally and functionally distinct

Hormones by the adrenal gland

- Mineralocorticoids (aldosterone)

- Glucocorticoids

- Androgen precursors

Mineralocorticoids (aldosterone)

- Zone glomerulosa

- Increases Na+ resorption (urine, sweat glands, salivary glands, colon), increased renal K+ excretion

Glucocorticoids

- Zone fasciculate

- Hyperglycemia, immunosuppression, increase lipolysis, decreased glucose uptake into skeletal muscle, increased gluconeogenesis, increased protein degradation

Androgen precursors

- Zona reticularis

- Converted to androgens; direct effects on testes and ovaries, bone-protective effects, increased neuron survival

Anatomy of adipose tissue

- Found under skin, around organs, in bone marrow, within muscle and breast tissue

- Composed predominantly of adipocytes along with fibroblasts, macrophages and endothelial cells

- Releases hormones (leptin (hormone that makes you feel full), adiponectin (modulates insulin response), resistin

- Main hormone functions: regulating body metabolism, weight, reproductive function and inflammation

Anatomy of the pancreas

- Lies beneath the greater curvature of the stomach and small intestine

- Bulk of mass is exocrine tissue/ducts

- Produces pancreatic juice and secretes it into the small intestine for digestion

- Clusters of endocrine cells are scattered throughout; produce insulin and glucagon

Types of endocrine cells in the islets of Langerhans

- a cells (20%): secrete glucagon

- b cells (70%): secrete insulin and amylin

- delta cells (3-10%): secrete somatostatin

- PP cells (3-5%): secrete pancreatic polypeptide

- E cells (1%): secrete ghrelin

Insulin structure

A and b chains held together by disulfide bonds

Insulin functions

- Secreted in response to increased blood glucose concentrations

- Insulin facilitates glucose entry into muscle, adipose and other tissues, through GLUT4

- Increases glucose in liver through multiple mechanisms

Structure of glucagon

- Synthesized as pro-glucagon in pancreatic a cells

- Proteolytically processed to yield glucagon

Functions of glucagon

- Secreted in response to low blood glucose concentrations

- Mainly affects the liver to increase blood glucose levels

- Stimulates breakdown of liver glycogen and stimulates gluconeogenesis

Decrease in GH release

Decrease in body mass

Decrease in TSH and the T3/T4 ratio

Loss of TSH regulated functions

Over-secretion of PTH

Loss of bone mass

Decrease in renal renin release

Decreased ability to regulate arterial blood pressure

Decrease in reproductive hormones

Reduced production of sperm, menopause

Decrease in thymus cytokines

Fewer mature, functional lymphocytes