The hypothalamus is the general director of the hormone system.

(1)

Hypothalamus

Hypothalamus - - pituitary pituitary - - adrenal glands adrenal glands

Magdalena Gibas-Dorna MD, PhD Dept. of Physiology University of Medical Sciences Poznań, Poland

(2)

The hypothalamus is the general director of the hormone system.

At every moment, the hypothalamus analyses messages coming from: the brain and different regions of the body.

Afterwards, it performs a number of functions, such as

maintaining a stable body temperature, controlling blood

pressure, ensuring a fluid balance, and even proper sleep

patterns.

(3)

Cell bodies of

neurons that produce releasing/inhibiting

hormones Hypothalamus

Primary capillaries in median eminence

Arterial flow

Releasing hormones Anterior pituitary hormone

Long Portal veins

Releasing/

inhibiting hormones

ANTERIOR PITUITARY

Secretory cells that produce anterior pituitary hormones

Anterior pituitary hormones

Venous outflow

Gonadotropic Thyroid-

Proactin hormones stimulating ACTH Growth (FSH and LH) hormone hormone

Hypothalamus Hypothalamus releases

hormones at median

eminence and sends to

pituitary via

portal vein

portal vein.

(4)

Function of the releasing and Function of the releasing and inhibitory

inhibitory hypothalamic hormones hypothalamic hormones

• Thyrotropin- releasing hormone (TRH) (TRH) - causes release of thyroid - stimulating hormone (TSH)

• Corticotropin - releasing hormone (CRH) (CRH) – causes release of ACTH

• Growth hormone releasing hormone (GHRH) (GHRH) - causes release of growth hormone, and

• Growth hormone inhibitory hormone (GHIH) (GHIH), , which is the same as the hormone somatostatin somatostatin and which inhibits the release of growth

hormone.

(5)

Function of the releasing and Function of the releasing and inhibitory

inhibitory hypothalamic hormones hypothalamic hormones

• Gonadotropin - releasing hormone (GnRH) (GnRH)

– causes release of the two gonadotropic hormones, LH and FSH

• Prolactin inhibitory hormone (PIH) (PIH) , ,

- belived to be dopamine - causes inhibition of prolactin release.

• PRL-releasing factor (PRF) (PRF). .

- belived to be TRH – increases prolactin release

(6)

The location of

The location of pituitary pituitary (hypophysis)

(hypophysis) relative to brain and relative to brain and hypohalamus

hypohalamus

(7)

Six very important hormones are Six very important hormones are

secreted by

secreted by anterior pituitary anterior pituitary :

• Secreted by lactotropes prolactin (PRL) (PRL)

• Secreted by thyrotropes

thyroid stimulating hormone (TSH)

(TSH)

• Secreted by gonadotropes follicle - stimulating hormone FSH, and luteinizing hormone FSH LH LH

• Secreted by corticotropes adrenocorticotropin (ACTH) (ACTH)

• Secreted by somatotropes growth hormone (GH; (GH;

somatotropin)

(8)

To venous circulation

Arterial blood supply Posterior pituitary Supraoptic

nucleus

Paraventricular nucleus

Hypothalamus

Posterior Posterior

pituitary pituitary

receives axons from the

supraoptic (→ADH) and

paraventricular nuclei

(→oxytocin).

(ADH)

(oxytocin)

(9)

Growth hormone Growth hormone

(somatotropin)

(10)

Somatomedins Liver Growth hormone Somatotrophs of Anterior pituitary

Somatostatin ( - ) GHRH

(+)

Portal vein Hypothalamus Sleep center In the brain

Chemical stimuli Stress centers

In the brain

• GHRH, somatostatin (GHIH) and ghrelin

control GH release

• pancreatic somatostatin has other functions

(inhibits hormone

secretion by α and β cells)

Ghrelin from stomach (+)

(-)

(+)

(11)

Sleep

Midnight 6 AM Noon 6 PM

Time of day Plasma GH

concentration (relative units)

GH is released in pulses, with a major GH is released in pulses, with a major

peak during deep sleep before RE

peak during deep sleep before RE M M

(12)

Physiology of growth

(13)

GH stimulates cartilage and bone GH stimulates cartilage and bone

growth by:

• increased deposition of protein by the deposition of protein

chondrocytic and osteogenic cells that cause bone growth

• increased rate of reproduction

reproduction of these cells

• the specific effect of converting chondrocytes

converting chondrocytes into osteogenic cells

into osteogenic cells, thus causing specific deposition

of new bone.

(14)

Direct and indirect effects of GH Direct and indirect effects of GH

• Direct effects are the

result of growth hormone binding its receptor on

target cells

• Indirect effects are

mediated primarily by an insulin

insulin - - like growth factor like growth factor - - 1 1 and 2

and 2 (IGF (IGF - - 1 1 ; IGF ; IGF - - 2 2 ), ),

hormones that are secreted from the liver and other

tissues in response to GH

(15)

Physiology of growth Physiology of growth

Growth is affected by:

• thyroid hormones

• androgens

• estrogens

• glucocorticoids

• insulin

• genetic factors

• adequate nutrition

sex hormones

(16)

Physiology of growth

Physiology of growth – – growth periods: growth periods:

• In humans, there are 2 periods of rapid growth, the first in infancy and the second in late puberty just before growth stops

• The first period is a continuation of the fetal growth period

• The second growth spurt is due to an interaction between sex steroids, GH, and IGF sex steroids, GH, and IGF -1 - 1

sex hormones

sex hormones →↑ →↑ amplitude of the spikes of GH amplitude of the spikes of GH secretion

secretion →↑ →↑ IGF- IGF - 1 1 →↑ →↑ growth growth

(17)

Although androgens and estrogens initially

stimulate growth, they finally terminate growth by causing the epiphyses to fuse to the long bones.

Two growth Two growth

periods

(18)

Metabolic effects of GH

(19)

Metabolic effects of GH Metabolic effects of GH

• Anabolic

• Increases fat utilisation for energy

• Elevates blood sugar

(20)

GH GH - -

summary

(21)

GIGANTISM GIGANTISM

• excessive production of GH before

adolescence

(22)

ACROMEGALY

ACROMEGALY – excessive production of GH after adolescence

Intradental separation and

prognathism in a patient with

acromegaly.

(23)

Acromegaly

(24)

The somatopause

The somatopause is directly related to the decline of growth hormone produced by the body during aging

• • Clinical Signs of Clinical Signs of the the Somatopause Somatopause : :

• Weight gain

• Energy Loss

• Skin wrinkling

• Decreasing muscle mass

• Loss of bone density

• Increasing body fat

(especially around the

waist)

(25)

GH - youth hormone?

• GH may reverse

biological effects of aging

• GH is not recommended for common use in adults

• GH supplementation:

- GHD

- AIDS wasting syndrome

- short bowel syndrome

(26)

Other hormones of anterior pituitary:

ACTH, TSH, FSH, LH, PRL

(27)

ACTH ACTH - - adrenocorticotropin adrenocorticotropin

regulates adrenocortical function regulates adrenocortical function

• stimulates cortisol (glucocorticoid) production by adrenal cortex

• stimulates aldosterone (mineralocorticoid) production

• ACTH also exhibits some extraadrenal effects - it has a pigmenting action (MSH activity)

• CRH, ACTH ACTH and cortisol secretion exhibit circadian

rhythmicity

(28)

TSH TSH stimulates the thyroid gland stimulates the thyroid gland folicles:

folicles:

• it activates all of the chemical processes that cause T4 T4 production and release

production and release by the thyroid gland

• the rate of TSH secretion by anterior pituitary is

controlled mainly by the negative feedback effect of

T4

(29)

FSH FSH functions: functions:

• • FSH FSH stimulates early growth of the ovarian follicle

• • FSH FSH stimulates

spermatogenesis

(30)

LH LH functions: functions:

• • LH LH stimulates ovulation and luteinization

• • LH LH stimulates

testosterone secretion

(31)

Prolactin

(32)

Hypothalamus Hypothalamus

Prolactin Oxytocin

Anterior pituitary

Posterior pituitary

Alveolus

Ductal system

Milk synthesis Milk synthesis

in alveoli in alveoli

Milk secretion from alveoli Milk secretion from alveoli

into ductal system into ductal system

Prolactin

Prolactin ↑milk synthesis and secretion

into alveoli Birth

↓ Prolactin,

↑ neural

control (breast mechanorec.) Suckling

Suckling Hypothal.

↑ Prolactin 1 hr

↑ Milk production

Effect weakens over

months

(33)

ADH ADH and oxytocin and oxytocin

- - posterior pituitary hormones posterior pituitary hormones

(34)

Hormones of t

Hormones of t he posterior he posterior pituitary gland

pituitary gland

• • Oxytocic hormone: Oxytocic hormone :

- it causes contraction especially of the uterus and to a lesser degree other smooth muscles of the body

- it stimulates myoepitelial cells in the breast myoepitelial cells causing milk ejection

- it also participates in the process of sperm

ejection

(35)

"Love hormone"

may also help us recognize faces

•

hormone associated with trust and social bonding (including pair- bond formation,

maternal behavior, sexual behavior)

• helps people

recognize familiar

human faces

(36)

Hypothalamus Hypothalamus

Prolactin Oxytocin

Anterior pituitary

Posterior pituitary

Alveolus

Ductal system

Milk synthesis Milk synthesis

in alveoli in alveoli

Milk secretion from alveoli Milk secretion from alveoli

into ductal system into ductal system

Suckling, baby sounds hypothal

↑ oxytocin

(paraventricular nucleus)

↑ myoepithel.

contract

milk let-down

(37)

Regulation of

Regulation of oxytocin oxytocin secretion secretion (paraventricular nucleus):

(paraventricular nucleus):

• suckling via stimulation of touch receptors in breast

• distension of female genital tract (during labour)

• pain

• psychological stimuli (baby’s cry, orgasm)

(38)

Hormones of t

Hormones of t he posterior he posterior pituitary gland

pituitary gland

• • Antidiuretic hormone Antidiuretic hormone (ADH; vasopressin): (ADH; vasopressin):

- increases the permeability of the kidney collecting ducts and tubules to water

(antidiuretic action)

- name „vasopressin” means that it works as a

vasoconstrictor

(39)

O O smoreceptors smoreceptors in in hypothalamus hypothalamus . .

measure the amount of fluid in your

blood at every moment you are alive.

(40)

Adrenal glands

(41)

Adrenal gland

Capsule

Medulla Zona

glomerulosa Zona

fasciculata Zona

reticularis Cortex

Location of adrenal glands adrenal glands

• the outer cortex cortex (80%) releases

steroids steroids;

• the inner medulla medulla (20%) releases

catecholamines

(42)

The adrenal cortex

The adrenal cortex – – three zones three zones

(43)

hormone (CRH)

(z. fasciculata)

(44)

Brain

NE and E

Blood Various

effector organs

NE

Heart Spinal cord

Adrenal

glands Medulla

Preganglionic

Sympathetic neurons

Sympathetic ganglia

Postganglionic sympathetic neuron

The anatomical analogy between cells of The anatomical analogy between cells of adrenal medulla and sympathetic adrenal medulla and sympathetic

postganglionic neurons postganglionic neurons

• Postganglionic fiber has effects on one specific effector organ, such as the heart.

• The cells of • The cells of adrenal medulla adrenal medulla

may influence the activity of various organs in the body (they secrete

hormones to the

circulation)

(45)

Adrenal catecholamines Adrenal catecholamines

The release of AK is carried out by direct connection of nerve fibers from

hypothalamus to intermediolateral cells

(IML), and then to adrenal medulla

(46)

The metabolic effects of The metabolic effects of catecholamines (similar to catecholamines (similar to

glucagon) glucagon):

• Increase blood sugar

• Increase rate of lipolysis

• Inhibition of protein degradation (eg. ↓proteolysis

in the muscle)

(47)

Liver

Lactate

Glycogenolysis

Muscle Blood Lactate

Glycogenolysis

Glucose

Glycerol

Lipolysis Adipose tissue Glucose

Fatty acids

EPI EPI raises glycogenolysis in liver/muscle and lipolysis in adipose; elevates blood glucose

Effects of epinephrine

(48)

The Fight or Flight System

(49)

Adrenergic responses

Adrenergic responses of selected tissues

Organ Receptor Effect

Heart

Blood vessels Kidney

Gut

Pancreas

Liver

Adipose tissue Skin

Bronchioles Uterus

Beta-1 Alpha Beta-2 Beta

Alpha, beta Alpha

Beta

Alpha, beta Beta

Alpha Beta-2

Alpha, beta

Increased inotropy Increased chronotropy Vasoconstriction

Vasodilation

Increased renin release Decreased motility

Increased sphincter tone Decreased insulin release Increased glucagon

release

Increased insulin and glucagon release

Increased glycogenolysis Increased lipolysis

Increased sweating Bronchodilation

Contraction, relaxation

(50)

Adrenal steroids

(51)

Cholesterol

Pregnenolone

Progesterone 17-OH-Pregnenolone

Dehydroepi- androsterone

Corticosterone

Aldosterone Cortisol

17-OH-Progesterone Testosterone

Estradiol

Adrenal hormones are derivatives Adrenal hormones are derivatives

of cholesterol

(52)

Glucocorticoids Glucocorticoids

Cortisol

(53)

Circadian

rhythms Stress

CRH

Hypothalamus

Anterior pituitary ACTH

Cortisol Adrenal cortex

Corticotropes in hypothalamus CRH CRH

portal pituitary ACTH ACTH

adrenal cortex cortisol

cortisol

Hypothalamic Hypothalamic – –

pituitary adrenal axis

(54)

Describe changes in human body that occur

during stress

(55)

Metabolic effects of Metabolic effects of

cortisol cortisol

• Catabolic

• Increase of lipolysis

• Increase blood sugar

(56)

Plasma

Cortisol

Amino acids

Cortisol

Muscle protein

The effects of cortisol on skeletal

muscle

(57)

Plasma Liver

Cortisol

Urea Urea

cycle Amino

acids

Glucose Glucose

Ammonia

Gluconeogenesis Amino acid

metabolizing enzymes

Glycogen synthesis

Cortisol accelerates liver urea cycle and amino acid conversion

to glucose glucose

The effects of cortisol on liver metabolism

(58)

Summary of effects of

Summary of effects of cortisol cortisol on metabolism:

on metabolism:

LIVER:

↑ gluconeogenesis, and glycogen synthesis

SKELETAL MUSCLE:

↓ protein synthesis;

↑ protein degradation;

↓ glucose uptake;

ADIPOSE TISSUE ADIPOSE TISSUE : :

↓ glucose uptake;

↑ lipid mobilization

(59)

Cushing

Cushing ′ ′ s syndrome s syndrome – – long lasting long lasting increase in plasma corticoids

increase in plasma corticoids

(60)

Cushing

Cushing ′ ′ s syndrome s syndrome

• skin and subdermal tissues are thin, and muscles are poorly developed

• wounds heal poorly and minor trauma causes bruises and ecchymoses

• very severe osteoporosis

• facial hair and acne

• obesity with „buffalo torso” and „moon face”

• adrenal diabetes

• 80% of patients have hypertension

• mental symptoms and sleep disorders

• reduced sex drive and fertility in man

• irregular or stopped

menstrual cycles in women

(61)

Obesity with Obesity with

„ „ buffalo torso buffalo torso ” ”

Acne Acne

(62)

Cushing syndrome

(63)

Mineralocorticoids Mineralocorticoids

Aldosterone

(z. glomerulosa)

If the aldosterone of ten million

people were pooled together, only one

gram of the hormone would result.

(64)

Effects of

Effects of mineralocorticoids mineralocorticoids : :

• • Na Na ⁺ ⁺ reabsorption in the collecting tubules reabsorption in the collecting tubules

• • K K ⁺ ⁺ and H and H ⁺ ⁺ loss with urine loss with urine

• reabsorption of Na ⁺ and the secretion of K ⁺ by salivary and sweat glands

• High aldosterone: hypokalemia, muscle weakness and mild alkalosis

Cells in the kidney channels (collecting

tubule)

(65)

Liver

Lung

Angiotensin- converting Enzyme (ACE) Renin

Kidney

Angiotensinogen

Angiotensin I

Angiotensin II

Aldosterone Zona glomerulosa

cells

Mineralocorticoids – RAA RAA system system

Decreased kidney blood pressure (↓ ECF) renin

converts

angiotensinogen to angiotensin I. Lung ACE converts

angiotensin I to II

angiotensin II stimulates

aldosterone release.

Aldosterone causes Na

⁺

and H

₂

O

retention, increase

in ECF and finally

inhibition of the

primary stimuli

(66)

Adrenal androgens

(67)

Effects of adrenal

Effects of adrenal androgens and androgens and estrogenes

estrogenes

• Androgens are the hormones responsible for masculinization

masculinization, and they also promote protein anabolism protein anabolism

and growth and growth

• They cause epiphyses to fuse in the long bones, thus eventually stopping growth

• They slightly increase Na Na ⁺ ⁺ , K , K ⁺ ⁺ , H , H ₂ ₂ O, O, Ca Ca ⁺⁺ ⁺⁺ , sulfate and phosphate , sulfate and phosphate retention

and they increase the size of the kidneys.

(68)

The androgenital syndrome:

• typical masculine characteristics:

• much deeper voice

• occasionally baldness

• masculine distribution of hair on the body

• masculine features

• • salt loosing form salt loosing form and hypertensive form

hypertensive form

(69)

The androgenital The androgenital

syndrome:

• Genitals of female baby masculinized by prenatal hypersecretion of

adrenal androgens

(70)

Adrenal insufficiency Adrenal insufficiency

Loss of glucocorticoid and

mineralocorticoid action –

predict the typical findings

(71)