endocrine system

1

The Endocrine System

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Outline

• Types of Regulatory Molecules• Endocrine Glands and Hormones• Paracrine Regulation• Hormones That Enter Cells• Hormones That Do Not Enter Cells• Posterior and Anterior Pituitary Gland• Thyroid and Parathyroid Glands• Adrenal Glands• Other Endocrine Glands

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SIGNALING AGENTS & FACTORS

Neurotransmitters

Peptides

Oxygen-based molecules, e.g., NO

Prostanoids

Hormones

Cytokines ( some are Chemokines)

Extracellular-matrix molecules

Nutrients & metabolites

Mechanical stimuli, e.g., fluid shear

Cell-surface glycoproteins

Hormones from endocrine cells & organs are part of a much larger picture of the outside controls on cells

Heat, osmolarity, exogenous chemicals, etc

ENDOCRINE

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Types of Regulatory Molecules

• Hormone – A regulatory chemical secreted into the blood by an endocrine gland, or an organ exhibiting endocrine function.

• Target Cells respond to hormone– Neurohormone – A chemical messenger

secreted by neuron into the blood rather than the synaptic cleft.

• Paracrine - regulatory molecules work without being transmitted by the blood – not endocrine

• Pheromone - communication messengers

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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Axon Neurotransmitter

Endocrine gland

Paracrine regulator

Receptor proteins

Hormonecarried by blood

Target cell

6

Endocrine Glands and Hormones• Hormones secreted by the endocrine glands belong to four

chemical categories:– Polypeptides - short chains of amino acids less than 100

amino acids (insulin & ADH)– Glycoproteins- longer than100 A.A. with carbs (FSH and LH)– Amines - Amines – A.A. derived from tyrosine and

tryptophan – epinephrine and norepinephrine and melatonin – Steroids - lipids derived from cholesterol

sex steroids - testosterone, estadiol, progesterone, and cortisol – secreted by testes, ovaries, placenta and adrenal cortex

Corticosteroids - adrenal cortex cortisol and aldosterone (regulates glucose and salt balance)

– All hormones can be categorized as lipophilic (fat soluble) or hydrophilic (water soluble).

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Endocrine Glands and Hormones• Neural and endocrine interactions

– Endocrine system also interacts and cooperates with the nervous system to regulate the activities of the other organ systems of the body.

– Secretory activity of many endocrine glands controlled by nervous system like

Adrenal medulla, posterior pituitary, and pineal gland

major site for neural regulation is the brain’s regulation of the anterior pituitary by the hypothalmus

However many are not under neural control

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Human Endocrine Systemmajor glands

9

cvlAl

re

uo

- - - - - - - diaphragm

Parathyroids

Adrenal cortex

Thyroid

Pituitary anterior

Pancreas

Gonads

ENDOCRINE ORGANS I

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[ non-epithelial origin ]

cvlAl

re

uo

- - - - - - - diaphragm

Parathyroids

Adrenal cortex

Thyroid

Pituitary anterior

Pancreas

Gonads

ENDOCRINE ORGANS II

[Pineal]

[Heart]

[Adrenal medulla]

[Kidney]

[Placenta]

Plus neuroendocrine cells developed within mature gut, airway, etc epithelia

[Pituitary, posterior & Brain]

[Adipose tissue]

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TYPICAL ENDOCRINE GLAND - Context

hormone release

vessels

Clumps of endocrine cells

blood

control

Capillary diffusion

TARGET ORGAN

Target cells, with receptors for binding

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transport3

4 5

Target cells’ response

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Feedback

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GLAND(S) WHERE CELL TYPES HORMONES SPECIAL

Thyroid Neck Follicular cells C cells

Thyronine Calcitonin

Follicles for storage

Parathyroid Neck Chief cells Parathormone /PTH

Small

Adrenal medulla

Over kidney

Chromaffin cells

Epinephrine Norepinephrine

Nerve fibers

Adrenal cortex

Over kidney

Zona glomerulosa Zona fasciculata Zona reticularis

Mineralocorticoids Glucocorticoids Sex steroids

Pineal Brain’s center

Pinealocytes Melatonin Connected for light drive

Zones

ENDOCRINE ORGANS I

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GLAND(S) WHERE CELL TYPES HORMONES SPECIAL

Pituitary posterior

Axons of PV & SO hypothal. neurons

Oxytocin Vasopressin /ADH

Extension of brain

Pancreas Left upper quad

Beta, Alpha, Delta, PP cells

Insulin Glucagon Somatostatin Pancr Peptide

Gonads Pelvic/ Scrotal

Granulosa, Theca Lutein, & Leydig

Sex steroids Inhibin

Placenta Uterus Syncytiotrophoblast Female: for amplified hormonal responses

Female: cyclic

Pituitary anterior

Below brain

MTs STs GTs THs CTs

Blood drains hypothal.-pituitary for control

Prolactin GH LH FSH TSH ACTH

Below brain

Islets

+Pituicytess

ENDOCRINE ORGANS II

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Paracrine Regulation

• Signaling between cells - Local effect and short-lived occurs in many organs

• Regulatory molecules– cytokines - regulate different cells of the

immune system– growth factors - promote growth and cell

division in specific organs – stimulate cell division at target cells

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Paracrine Regulation• Prostaglandins – most diverse group of paracrine regulators• participate in regulation of:

– immune system – inflammation, pain and fever– reproductive system – reproductive function ovulation,

labor, – digestive system – inhibit gastric secretions, incrfease

motility and fluid absorption – respiratory system - blood vessels constriction and dilation

in lungs– circulatory system - blood platelets in blood clotting– urinary system - renal blood flow vasodilation increasing

urine excretion• Prostaglandin synthesis inhibited by aspirin.

– nonsteroidal anti-inflammatory drug Ibuprofen Work to inhibit inflammation and pain by inhibiting

enzyme necessary to produce prostaglandins – (cyclooxygenase -2)

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Hormones That Enter Cells

• Lipophilic hormones pass through the target cell’s plasma membrane and bind to intracellular receptor proteins.

– hormone receptor complex then binds to specific regions of DNA

activate genes and regulate target cells

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Steroid Hormone Action

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Hormones That Do Not Enter Cells

• Hormones that are too large or too polar to cross plasma membranes include all of the peptide and glycoprotein hormones, as well as catecholamine hormones epinephrine and norepinephrine.

– bind to receptor proteins located on the outer surface of the plasma membrane

cyclic AMP second-messenger system IP3/CA++ second-messenger system

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Action of Epinephrine on a Liver Cell

1. Epinephrine is lipophobic and needs to bind to specific receptor proteins on cell surface.

2. Acting through intermediary G proteins the hormone bound receptor activates the enzyme adenenylyl cyclase which converts ATP to cAMP

3. Cyclic AMP performs as a 2ndary messenger and activates protein kinase-A an enzyme that was previously inactive

4. Protein kinase–A phosphorylates and activates the enzyme phosphorylase which catalyses the hydrolysis of glycogen into glucose.

20

IP3/CA++ Second-Messenger System

1. The hormone epinephrine binds to specific receptor proteins on the cell surface.

2. Acting through G- proteins, the hormone-bound receptor activates the enzyme phospholipase C, which converts membrane phospholipids into inositol triphosphate (IP3)

3. IP3 diffuses thru the cytoplasm

and binds to receptors on the endoplasmic reticulum

4. The binding of IP3 to the receptor stimulates the endoplasmic reticulum to release Ca++ into the cytoplasm

5. Some of the released Ca++ binds to the receptor protein called calmodulin

6. The Ca++/Calmodulin complex activates other intracellular proteins – producing the horomone effects

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Primary endocrine organs

• Hypothalamus and pituitary gland secrete hormones and regulate other endocrine organs. They are the main regulatory organs of the endocrine system.

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Hypothalamus

• Located below the thalamus and above the pituitary gland (=epiphysis)

• Regulates the pituitary gland secretions through two different mechanisms

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Hypothalamus - neurohypophysis

• 1- Neurons, receiving information from receptors, fire APs which travel down to the post pituitary gland and stimulate the release of stored neurohormones – Oxytocin (OT) and anti-diuretic hormone (ADH)

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Hormones of the posterior pituitary

Regulation Hormone Target organ Action Pathology

Reflex Oxytocin - Uterus (smooth muscle)- breast tubules (smooth muscles)

-labor and delivery

- milk-let down

----

Reflex (osmoreceptor) ADH (vasopressin)

- DCT in kidney tubules

- promote H2O reabsorption

- not enough: diabetes insipidus- too much: ↑ BP?

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Hypothalamus – adenohypophysis

• 2- Upon stimulation, secretory cells located in the hypothalamus secrete “releasing” hormones which travel down a capillary bed toward the anterior pituitary gland (adenopituitary). Each type of releasing hormones will stimulate the secretion and release of a pituitary hormone.

• Hormones which control the secretion of other hormones are tropic hormones (found in hypothalamus and pituitary gland

26Figure 6.5

Hormones of the hypothalamus and anterior pituitary gland

27Figure 6.8

Anterior pituitary

Regulation Hormone Target organ Action Pathology

GHRH and GHIH Growth hormone (GH) Many cells (bones..)

Stimulate cell growth and cell division

- not enough: children pituitary dwarfismtoo much: gigantism (children) – acromegaly (adult)

PRH - PIH Prolactin (PL) Breast secretory cells

- milk secretion

--

TRH Thyroid stimulating hormone (TSH)

Thyroid gland - promote thyroid gland secretion (T3 and T4)

- not enough: hypothyroidism (cretinism in children)- too much: hyperthyroidism

CRH Adrenocorticotropic hormone (ACTH)

Adrenal cortex (3 layers)

- stimulates secretion of adrenal cortex

- not enough: Addison's disease- too much: Cushing syndrome

GnRH Gonadotropin- Follicle stimulating hormone (FSH)- Luteinizing hormone (LH)

Stimulate gamete maturation

Stimulate gonadal gland secretion and gamete formation

- infertility

28Figure 23-17

Same Individual with Acromegaly (evolution over 20 years)

29Figure 6.6

Mechanism of control

30

HYPOPHYSIS/ Pituitary gland

Pituitary stalk

Posterior lobe

Hypoth alamus

Anterior lobe

Dura

IIIrd Ve

Interm

ediate lo

be

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Pars nervosa Infundibular process

Pars intermedia

PITUITARY SUB-DIVISIONS

Hypothalamic SO & PV nuclei

Hypothalamic median eminenceADENOHYPOPHYSIS

Pars distalis

Pars tuberalis

NEUROHYPOPHYSIS

Infundibular stem neural part of stalk

1

3

2

1

2

3

32

Unlike some other endocrine cells, those of the anterior pituitary separate their supplying a hormone from the detection of the need for the hormone.

The sensitivity to need is performed by hypothalamic neurons, which can coordinate requirements for several hormones with drives, and events outside the person.

Anterior-pituitary cells & hormones

The system also allows for control by inhibitory factors, as well as + driving hormone-releasing factors

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HYPOTHALAMO-HYPOPHYSEAL Portal flow

Superior arteries

Portal drainage

Hypothalamus

Anterior lobe capillaries

Dura

Hypothalamic capillary bed

Neurosecretory neurons

Veins

1

2

3

4

5

A portal flow takes venous blood drained from one organ and uses it as a supply to another organ, e.g., gut to liver

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HYPOTHALAMO-HYPOPHYSEAL Portal flow

Superior arteries

Portal drainage

Hypothalamus

Anterior lobe capillaries

Hypothalamic capillary bed

Neurosecretory neurons

Veins

1

2

3

4

5

Portal flow carries factors from hypothalamic neurons to pituitary anterior-lobe cells

E.g.,TH-RF from neuron causes

Thyrotroph to release TSH

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Superior arteries

Portal drainage

Hypothalamus

Anterior lobe capillaries

Hypothalamic capillary bed

Neurosecretory neurons

Veins

1

2

3

4

5

Mammotrophs MTs Somatotrophs STs Gonadotrophs GTs Thyrotrophs THs Corticotrophs CTs

Blood drains hypothalamus-pituitary for control by RFs, etc

Prolactin PRL Growth hormone GH Luteinizing hormone LH Follicle-stimulating hormone FSH Thyroid-stimulating hormone TSH Adrenocorticotrophic hormone ACTH

Anterior-pituitary cells & hormones

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Mammotrophs MTs

Somatotrophs STs

Gonadotrophs GTs

Thyrotrophs THs

Corticotrophs CTs

Blood drains hypothalamus-pituitary for control by RFs, etc

Prolactin PRL

Growth hormone GH

Luteinizing hormone LH/ICSH Follicle-stimulating hormone FSH

Thyroid-stimulating hormone TSH

Adrenocorticotrophic hormone ACTH cleaved from pro-opio-melanonocortin/ POMC

Anterior-pituitary cells & hormones

Acidophil

Basophil

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Anterior-pituitary cells 2Mammotrophs MTs

Somatotrophs STs

Gonadotrophs GTs

Thyrotrophs THs

Corticotrophs CTs

Prolactin PRL

Growth hormone GH

Luteinizing hormone LH FSH

TSH

ACTH

Acidophil Basophil Chromophobe

Chromophobes stain weakly, in comparison to CHROMOPHILS - Acidophils & Basophils

Folliculo-Stellate cells lie amongst the glandular cells; doing what?

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Anterior-pituitary cells 3

Corticotrophs CTs ACTH

but by selective enzymatic cleavage of a larger 32kDa precursor - pro-opiomelanocortin, also made in the hypothalamus and elsewhere, and there serving to provide other hormones & neurotransmitters

Pro-opiomelanocortin

ACTH

Pro-ACTH -LPH

-Endorphin

-MSH

SP

simplified

POMC ~ Pro-opiomelanocortin

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Anterior-pituitary cells 4Selective enzymatic cleavage of the precursor - pro-opiomelanocortin, provides other hormones & transmitters

ACTH

-Endorphin

Pro-opiomelanocortinSP

NT 1-76

-LPHACTH

-LPHACTH

-LPH

NT 1-49

JP

-MSH

-MSH -MSH

elaborate

MSH ~ Melanocyte-stimulating hormone

NT ~ amino-terminal peptides

LPH ~ Lipotropic hormonePro-hormone convertase 1

Pro-hormone convertase 1

Pro-MSH

Pro-MSH

After Reudelhuber TL. J Clin Invest 2003;111:1115-1116

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NEUROHYPOPHYSIS

Pars nervosa

Hypothalamic SO & PV nuclei Supraoptic & Paraventricular nuclei

Hypothalamus 1

2

3

Inferior arteries

Veins

Release of hormone is separated from production

*

*

*

* Neural stalk

Optic chiasm

41

NEUROHYPOPHYSIS

Pars nervosa

Hypothalamic SO & PV nuclei Supraoptic & Paraventricular nuclei

Hypothalamus 1

2

3

Inferior arteries

Veins

*

*

Neural stalk

Optic chiasm

Note - the supraoptic nucleus is above the optic nerve & chiasm, but closer to the chiasm is the small suprachiasmatic nucleus (relaying the darkness stimulus indirectly to the pineal gland).

42

NEUROHYPOPHYSIS

Pars nervosa axons, terminals, pituicytes & capillaries

Hypothalamic SO & PV nucleiHypothalamus

Infundibular stem neural part of stalk - axons & glia

1

2

3

Neurosecretory neurons producing oxytocin & vasopressin/ADH

Inferior arteries

Veins

Release of hormone is separated from production

* *

*

*

43

NEUROHYPOPHYSIS

Hypothalamic SO & PV nucleiHypothalamus Neurosecretory neurons producing oxytocin & vasopressin/ADH

Inferior arteries

Veins

Hormone travels down the axon bound to the carrier protein - neurophysin, from which it is cleaved for release

*

*

44

SUCKLING REFLEXHypothalamic SO & PV neuron activation

Hypothalamus

*

BREAST

Myoepithelial-cell contraction

Sensory response

Oxytocin releaseStimulus1

23

4

56

7 Milk ejectionVascular transfer

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PITUITARY Mid-sagittal section of 1-m embryo

STOMODEUM

PHARYNGEAL ARCHES

PITUITARY

RATHKE’S POUCH

starting in oral ectoderm

BRAINI II

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PITUITARY DEVELOPMENT II Neural-tube diencephalic ectoderm

Oral-pharyngeal lining ectoderm

IIIrd Ve

Rathke’s pouch

Pars tuberalis

Pars distalis

Pars intermedia

Pars nervosa

Infundibular stem

Hypothalamus

ADENOHYPOPHYSIS

NEUROHYPOPHYSIS

47

PITUITARY DEVELOPMENT II

Pars tuberalis

Pars distalis

Pars intermedia

Pars nervosa

Infundibular stem

Hypothalamus

Pars nervosa Infundibular process

Pars intermedia

Hypothalamic SO & PV nuclei

Hypothalamic median

eminenceADENOHYPOPHYSIS

Pars distalis

Pars tuberalis

NEUROHYPOPHYSIS

Infundibular stem neural part of stalk1

3

2

1

2

3

CystsCysts in Pars intermedia - remnants of Rathke’s pouch lumen?

Rathke’s pouch lumen

48

Pars nervosa/ Infundibular process

Pars intermedia

Hypothalamic SO & PV nuclei

Hypothalamic median eminence

ADENOHYPOPHYSIS

Pars distalis

Pars tuberalis

NEUROHYPOPHYSIS

Infundibular stem/ neural part of stalk1

3

2

1

2

3

CystsCysts in Pars intermedia - remnants of Rathke’s pouch lumen?

49

Posterior Pituitary Gland

• Pituitary gland hangs by a stalk from the hypothalamus of the brain.

– anterior pituitary - appears glandular– posterior pituitary - appears fibrous

• Neurons produce antidiuretic hormone (ADH) and oxytocin.

– stored in, and released from, the posterior pituitary gland in response to neural stimulation from the hypothalamus

50

Effects of ADH

51

Anterior Pituitary Gland• Develops from a pouch of epithelial tissue that pinches off the

roof of the embryo’s mouth.– produces the hormones it secretes:

growth hormone (GH) stimulates muscles and bones to grow

adrenocorticotropic hormone (ACTH) regulates glucose homeostasis

thyroid-stimulating hormone (TSH) stimulates the production of thyroxin by thyroid gland

luteinizing hormone (LH) ovulation and testosterone production in testes

follicle-stimulating hormone (FSH) develops ovarian follicle and sperm in males

prolactin (PRL) stimulates mammary glands to produce milk melanocyte-stimulating hormone (MSH) synthesis and

dispersion of melanin pigment

52

Major Pituitary Gland Hormones

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Anterior Pituitary Gland

• Hypothalamic control of anterior pituitary gland secretion

– Neurons in the hypothalamus secrete releasing hormones and inhibiting hormones into blood capillaries at the base of the hypothalamus.

Each hormone delivered by hypothalamohypophysial portal system regulates secretion or inhibition of a specific anterior pituitary hormone.

54

Neurons in the hypothalamus secretes hormones that are carried by short blood vessels directly to the ant. Pituitary gland, where they either stimulate

or inhibit the secretions of the ant pituitary hormonesCell body

Axons toprimarycapillaries

Primarycapillaries

Pituitary stalk

Posterior pituitary

Anterior pituitary

Secondarycapillaries

Portalvenules

55

Anterior Pituitary Gland

• Negative feedback inhibition acts to maintain relatively constant levels of the target cell hormone.

– Positive feedback cannot maintain constancy of the internal environment.

56

Negative Feedback Inhibition

Hormones secreted by some endocrine glands feed back to inhibit the secretion of hypothalamic releasing hormones and anterior pituitary hormones

57

Thyroid and Parathyroid Glands

• Thyroid gland– Shaped like a shield and lies just below the

Adam’s apple in the front of the neck. Thyroxine helps set basal metabolic rate

by stimulating the rate of cell respiration. In children, thyroid hormones also

promote growth and stimulate maturation of the central nervous system.

unique function in amphibians - metamorphosis from larvae into adults

58

Regulation of Thyroxine Secretion

59

Thyroid and Parathyroid Glands

• Parathyroid gland and calcium homeostasis– four small glands attached to the thyroid

produces parathyroid hormone (PTH)one of only two hormones in humans

that are absolutely essential for survivalstimulates osteoclasts in bone to

dissolve calcium phosphate crystals and release Ca++ into the blood

60

Regulation of Blood Calcium Levels

61

Calcium Metabolism:

Figure 23-20: Calcium balance in the body

62Figure 19.20

63

THYROID GLAND

Follicular cells simple cuboidal epithelium

Colloid / Thyroglobulin

glycoprotein = PAS+

Follicles for storage

C cells/ Parafollicular cells

Capillaries

In the section, the follicles do not hold their spherical shape this well, and the colloid displays knife chatters and variable staining

64

THYROID GLAND: Physiological variablity

Follicular cells high cuboidal when very active; squamous when inactive

Colloid / Thyroglobulin less in active state, excessive in goitre

Follicles - size

varies inversely with activity

C cells/ Parafollicular cells for calcitonin

Capillaries

65

GOLGI

Amino acids

Sugars

Iodine

Thyroglobulin

Endocytosis

Cleavage

Release of hormones T3 & T4

Synthesis & iodination of thyroglobulin

THYROID FOLLICULAR CELL

TSH

66

Goiter

• Both hypo and hyperthyroidism can have goiter as a symptom

• Goiter is a swelling of the neck due to hypertrophy of the thyroid gland

• How can one explain that?

67

Goiter in hypothyroidism

• Most often due to a lack of dietary iodine

• The thyroid hormone is unable to synthesize a functional thyroid hormone (T3 and T4)

• The person express symptoms of hypothyroidism

• The nonfunctional T3/T4 cannot promote a negative feedback on TRH and TSH

the hypotalamus and pituitary gland increase their secretions the thyroid gland is stimulated to secrete more T3 and T4 …

• In children, the lack of functional T3/T4 result in cretinism, a form a mental retardation

68

Goiter in hyperthyroidism

• The cells secreting TRH or TSH on the hypothalamus and pituitary gland (respectively) have become abnormal and no longer are sensitive to the negative feedback they continue to secrete TRH or TSH continuous stimulation of the thyroid gland with excess thyroid hormones being formed

symptoms of hyperthyroidism

69

PARATHYROID GLAND

Oxyphil cells

Chief cells

Characteristic is the lack of obvious general structural features

Small, pale, resemble lymphocytes, but have more cytoplasm

Larger, eosinophilic, darker nuclei, packed with mitochondria

70

PARATHYROID GLAND

OXYPHIL CELLS

CHIEF CELLShave membrane calcium sensors to respond to low Ca2+ by releasing parathyroid hormone /PTH. PTH stimulates osteoclasts to release Ca2+ from bone & has conserving renal effects

derivatives of Chief cells

71

Osteoclast

Ruffled border agitating released enzymes & acid

Eaten-out hole is a Howship’s lacuna

BONE REMODELING

Osteoclasts as a team eating out a resorption tunnel

Sealing ring of tight attachment to bone

BONE MATRIX

BONE

72

ONCOCYTIC CONVERSION

As cuboidal epithelia and glands age, a few of their epithelial cells lose most of their normal organelles and fill up with mitochondria. Mitochondria-rich cells are eosinophilic.

This event results in two classes of cell:

those that are functioning normally and need many mitochondria - gastric parietal cells, renal proximal-tubular cells, striated-duct cells, etc; &

non-functional mitochondria-stuffed cells in older epithelia. These have acquired two names: the usual - oncocyte, and, as an exception, the archaic oxyphil cell in the parathyroids. & Hurthle cells

in thyroid

:

73

Adrenal Glands

• Adrenal glands are located above each kidney.

– Each gland composed of inner portion (adrenal medulla) and outer layer (adrenal cortex).

• Adrenal medulla– receives neural input from axons of

sympathetic division of the autonomic nervous system, and secretes epinephrine and norepinephrine in response

74

Adrenal Glands

• Adrenal cortex– Hormones from adrenal cortex are

collectively referred to as corticosteroids. Cortisol maintains glucose homeostasis,

and modulates some aspects of the immune response.

Aldosterone stimulates the kidneys to reabsorb Na+ and secrete K+ into the urine.

75

Adrenal Glands

76

Cortex

Medulla

Capsule

Adrenal vein

ADRENAL/SUPRARENAL GLAND

The adrenal embryologically is a composite of the:

medulla derived from ectoder mal neural-crest cells; &

cortex formed from mesoder m next to the mesonephros

77

ADRENAL CORTEXCortex

Zona glomerulosa

Zona fasciculata

Zona reticularis

]

]

small balls of cells

straight bundles of paler cells

cords of cells in a network

sparse Stroma of reticular fibers & vessels

Capsule

78

ADRENAL CORTICAL HORMONES

Cortex

Zona glomerulosa

Zona fasciculata

Zona reticularis

]

]

makes mineralocorticoids, e.g., aldosterone

makes glucocorticoids, e.g., cortisol

makes sex steroids, e.g., androstenedione

79

Zona glomerulosa regulated by Renin-angiotensin system

Zona fasciculata driven by ACTH

Zona reticularis driven by LH & ACTH

]

]

to make & release mineralocorticoids

to make glucocorticoids

to make sex steroids* & glucocorticoids

Zona-fasciculata steroid-synthesizing cell

Cholesterol droplets (often dissolved out)

Smooth ER, often tubular (bag-of-worms visual effect)

Mitochondria with tubular cristae

dehydroepiandrosterone*

80

Zona glomerulosa regulated by Renin-angiotensin system

mineralocorticoids

glucocorticoids

sex steroids* & glucocorticoids

]

]Zona reticularis driven by LH & ACTH

Zona fasciculata driven by ACTH

81

Zona-fasciculata steroid-synthesizing cell

Cholesterol droplets (often dissolved out)

Smooth ER, often tubular (bag-of-worms visual effect)

Mitochondria with tubular cristae

Inner mitochondrial membrane has a P450 enzyme for steroid biosynthesis

82

Zona glomerulosa ]

JG cellsRenin

Converting Enzyme

DISTAL TUBULE

Angiotensinogen

Angiotensin I

Angiotensin II

Aldosterone

Vasoconstriction

Sodium + water reabsorption (so blood pressure up)

JUXTAGLOMERULAR APPARATUS 6

Outside kidney

Renin is a protease

83

Aldosterone

Zona glomerulosa

JG cellsRenin

Converting Enzyme/ ACE

Angiotensinogen

Angiotensin I

Angiotensin II

Vasoconstriction

RENIN-ANGIOTENSIN SYSTEM

DISTAL TUBULE

Outside kidney

ACE is in many tissues, and the angiotensin II receptor is widespread, so that the RA system is very endocrine in affecting most of the body, not just vessels, adrenal & kidney

84

ADRENAL MEDULLA

Chromaffin cells

Sympathetic axons

Central vein

Occasional neuron

terminating mainly on chromaffin cells

Chromaffin cells so named, because of chromaffin reaction - a brown darkening of medulla seen when catecholamines react with dichromate & other oxidising agents

85

ADRENAL MEDULLA

Chromaffin cells make epinephrine & norepinephrine

Sympathetic axons

Central vein

Occasional neuron

terminating mainly on chromaffin cells

Epinephrine & norepinephrine are catecholamines stored, in association with the protein chromogranin, in dense-cored granules/ vesicles. E & NE augment sympathetic autonomic nervous-system actions

86

CATECHOLAMINE SYNTHESIS

Chromaffin cells make epinephrine & norepinephrine

TYROSINE

tyrosine hydroxylase

DOPA/Dihydroxyphenylalanine

DOPAMINE

aromatic L-amino acid decarboxylase/AADC

dopamine -hydroxylase/DBH

NOREPINEPHRINE

EPINEPHRINE/Adrenalin

phenylethanolamine-N-methyltransferase

[rate-limiting?]

87Figure 6.12b

88Figure 21.15

89

Adrenal gland hormones

Regulation Glands Hormones Target organs

Action Pathology

Reflex Adrenal medulla Epinephrine ANS target organs

Fight/flight Stress

Blood Pressure Adrenal cortex - Mineralocorticoid = aldosterone

DCT from renal tubule

- promote sodium reabsorption

Not enough" Addison disease

CRH ACTH Glucocorticoid = cortisone

Many cells Mobilize fuels – stress adaptation

Excess hormone: Cushing syndrome

GnRH GN Estrogen Testosterone

Sexual organs - Sex organ maintenance- Gamete development

Infertility

90

91

Pancreas

• Located adjacent to the stomach and is connected to the duodenum by the pancreatic duct.

– Secretes bicarbonate ions and a variety of digestive enzymes into small intestine.

cells of islets of Langerhans secrete insulin, and cells secrete glucagon.

antagonistic Insulin lowers while glucogen

raises blood glucose.

92

PANCREASDuodenum

Exocrine acini digestive enzymes

Lobule

}

Endocrine islet metabolic hormones

Ducts alkaline ions

Enteroendocrine cells hormones

93

Islet of Langerhans

ISLET: Cell types & products

Beta cell - insulin (majority)

Alpha cell - Glucagon

Delta cell - Somatostatin

PP cell - Pancreatic polypeptide

Beta & Alpha cells are directly sensitive to glucose level

94

Antagonistic Actions of Insulin and Glucagon

95

Glucose regulation

• Glucose level controlled by insulin and glucagon

• Insulin promotes a decrease in blood glucose

• Glucagon promotes an increase in blood glucose

96

Glucose regulation

97Figure 3.21

Fate of glucose

98

Diabetes mellitus

• Type I: autoimmune disease beta cells of the islets of Langerhans are destroyed by antibodies

• Type II: The cells become insulin-resistant glucose does not enter the cells as readily

99

Diabetic foot

100

Other Endocrine Glands

• Ovaries and testes– produce androgen

secondary sexual characteristics• Pineal gland

– secretes melatonin regulates biological clocks

101

Other Endocrine Glands

• Molting and metamorphosis in insects– Hormone secretions influence both

molting and metamorphosis in insects. Brain hormone stimulates production of

ecdysone (molting hormone).high levels cause molting to occur

juvenile hormonehigh levels prevent transformation to

an adult

102

Other Endocrine Glands

• Endocrine disrupting chemicals– chemicals that interfere with hormone

function Any chemical that can bind to receptor

proteins and mimic the effects of the hormone is called a hormone agonist.

Any chemical that binds to receptor proteins and has no effect, but blocks the hormone from binding is a hormone antagonist.

103

Cerebral Cortex

Cerebellum

Pineal gland

Brain Stem

Eye & optic nerve

Central sympathetic pathways

Suprachiasmatic nucleus

Thoracic cord

Sympathetic preganglionic

S Cervical ganglion

Sympathetic postganglionics

PINEAL ACTIVATION PATHWAY

13

4

2

5

7

Darkness increases HIOMT enzyme to make melatonin

HydroxyIndole-O-MethylTransferase

1 7

6

104

Cerebral Cortex

Cerebellum

Pineal gland

Brain Stem

Eye & optic nerve

Central sympathetic pathways

Suprachiasmatic nucleus

Thoracic cord

Sympathetic preganglionic

S Cervical ganglion

Sympathetic postganglionics

PINEAL ACTIVATION PATHWAY

13

4

2

5

6

1 7

7 melatonin

light offMelanopsin in retinal ganglion cells is the photosensitive mediator

105

Cerebral Cortex

Cerebellum

PINEAL GLAND

Brain Stem

Eye & optic nerve

Central sympathetic pathways

Suprachiasmatic nucleus

Thoracic cord

Sympathetic preganglionic

S Cervical ganglion

Sympathetic postganglionics

PINEAL ACTIVATION PATHWAY

13

4

2

5

7

Darkness increases HIOMT enzyme to make melatonin HydroxyIndole-O-MethylTransferase

6

melatonin

light off

106

cvlAl

re

uo

- - - - - - -

ENDOCRINE ORGANS II

Plus neuroendocrine cells developed within mature gut, airway, etc epithelia

[Kidney]

[Heart] ANF

EPO Renin

VIP Gastrin Secretin, etc

Gonads

[Placenta]hCG Estrogen Progesterone

Sex steroids

[Adipose tissue]

Leptin

107

ATRIAL HEART & ANF

Atrial myocytes have a well developed Golgi complex and secretory granules

Reticular fiber

Atrial Natriuretic Factor (ANF) in the granules STIMULATES:

diuresis; sodium excretion (natriuresis); vasorelaxation;

& INHIBITS the Renin-Angiotensin system & aldosterone secretion

108

Enteroendocrine cell types I

Enteroendocrine cell small, pale, few; granules are located basally for release into the lamina propria

Entero is misleading because: some cell types are confined to the stomach; and peptides & amines are signaling agents in other epithelia and other systems e.g. brain

G cell - gastrin

S cell - secretin

I cell - cholecystokinin

ECL cell - histamine

D cell (antral) - somatostatin

EC cell - serotonin

A cell - ghrelin

109

Enteroendocrine cell types II

Motilin cell: why not ‘M’ cell? There already is one, involved in immunity

G cell - gastrin

S cell - secretin

I cell - cholecystokinin

ECL cell - histamine

L cell - glucagon-like peptide (GLP-1 & 2) peptide Y (PYY) oxyntomodulin

K cell - gastric inhibitory polypeptide/GIP

N cell - neurotensin

M? cell - motilin

D cell (antral) - somatostatinCoordinated with extrinsic & intrinsic neural controls and interacting amongst themselves

EC cell - serotonin

A cell - ghrelin

110

EXOCRINE PANCREAS Controls

Duodenum

Exocrine aciniEnteroendocrine cellsSecretin & CCK

digestive enzymes

HCO3- ions

RESPONSE

Acid Fats Peptides

STIMULI

CONTROLLER

+ Vagal cholinergic control

111

SOURCES OF ‘GUT’ HORMONES

RECTUM

LIVER

PANCREAS

GALL BLADDER

STOMACH

SMALL GUT

LARGE GUT

Bile

gastrin ghrelin

Duodenumcholecystokinin motilin

somatostatin

neurotensin

GIP-1

GLP-1&2 Peptide Y

insulin glucagonPPY somatostatin

secretin

Oxyntomodulin

112

SOURCES OF ‘GUT’ HORMONES

PANCREAS

STOMACH

SMALL GUT

LARGE GUT

gastrin ghrelin

Duodenum cholecystokinin motilin

somatostatin

neurotensin

GIP-1

GLP-1&2 Peptide Y

insulin glucagon PPY somatostatin

secretin

Oxyntomodulin

113

Enteroendocrine cell types III

Immunostaining for the peptide or chromogranin and fluorescence methods for the amine derivatives now provide clear identification of the cells, but against a background of the old silver-based cell nomenclature

A messy story*, because of the various staining reactions of enteroendocrine cells (particularly with silver methods) based on the peptide hormones, the associated chromogranin storage protein in the granules, and any catecholamine, serotonin or histamine content.

ECL cell - EnteroChromaffin-Like cell

114

Adipocyte hormones & other metabolic players

RECTUM

LARGE GUTLIVER

SMALL GUT

STOMACH PANCREAS

GALL BLADDER

ES

OP

HA

GU

S

MOUTH

APPENDI X

SALIVARY GLAND

AIRWAY

HYPOTHALAMUS Appetites

Homeostasis Emotion

CEREBRAL CORTEX

Cerebellum

Pons

Mid-brain

Medulla

PITUITARY

TALUS

CALCANEUS Metatarsal

FEMUR

Fat cell

Adipocytes

MUSCLE

115

Adipocyte hormones -

LIVER

HYPOTHALAMUS

TALUS

CALCANEUS Metatarsal

FEMUR

Fat cell

Adipocytes

MUSCLE

LEPTIN

ADIPONECTIN

for energy balance and glucose homeostasis

116

Visceral/abdominal fat & type II diabetes, etc

LIVER

HYPOTHALAMUS

TALUS

CALCANEUS Metatarsal

FEMUR

Fat cell

Adipocytes

MUSCLE

LEPTIN

ADIPONECTIN

MACROPHAGES(Ms)

Macrophages accumulate in the stroma of the fatty tissue, become activated to release abnormal cytokines , e.g., TNF-,that disrupt many metabolic pathways

so that the visceral adipose tissue is permanently inflamed and dangerous, e.g.

Adipocyte production of adiponectin falls

Insulin signalling goes bad, etc.

117

TESTIS & LEYDIG CELLS

Peritubular myoid cells

LEYDIG INTERSTITIAL CELLSAcidophil Much smooth ER Lipid droplets Crystals of Reinke

SERTOLI CELLS

Sperm

layered SPERMATOGENIC CELLS

{

stratified germinal epithelium

BASAL LAMINA

SEMINIFEROUS TUBULE

SEMINIFEROUS TUBULE

118

HORMONESPITUITARY GONADOTROPHS

HYPOTHALAMIC NEURONS

INTERSTITIAL CELLS

SEMINIFEROUS TUBULE

PENIS

SEMINAL VESICLE

PROSTATE

RETE TESTIS

TUBULUS RECTUS EFFERENT

DUCT

EPIDIDYMIS

DUCTUS DEFERNS

BULBOURETHRAL GLAND

urethra

Androgens

Courtship & Coital behaviors

GnRHFSH

LH

1

2 34

5 Secondary sexual characters

67

Somatic growth & metabolism