Neuro-endocrine

Integration

M Y Sukkar, 2003
 Neuro-endocrine integration
 Hypothalamus & limbic system
 Anterior pituitary
 Posterior pituitary
 Pineal gland
 Adrenal medulla
 Hypothalamus & limbic system
 Hypothalamic nuclei : a major site of
neuro-endocrine integration
 Concerned with control of vegetative
(visceral functions) thro autonomic
nervous system e.g:
 CVS, GIT, TEMP. REG., REPRODUCTION
 Hypothalamus forms part of the
limbic system
 Control of emotions
 Effects on behavior & visceral functions
 The pituitary gland

 Anterior pituitary
 Posterior pituitary
close connections with

hypothalamus
 Nerve tracts to  Posterior lobe
 Portal vessels to  anterior lobe
Hypothalamo-hypophyseal
Tracts
Hpothalamo-hypophyseal tracts
 From supraoptic nucleus
 &From paraventricular nucleus
 These nerve tracts transport
vasopressin (ADH) & oxytocin to be
stored in nerve terminals in posterior
lobe
 The hormones are released in
response to electricals ignals in the
nerve tracts
 Neuro-hormonal reflexes
Hypothalamo-hypophyseal
portal vessels
 Hypothalamo-hypophyseal
portal vessels
 Portal vessels start in capillaries
in the median eminence of hypo-
thalamus
 End in capillaries (sinusoids) in
the anterior lobe around the cells
 Carry hypothalamic releasing &
inhibitory hormones to control
the anterior pituitary hormones
 Hypothalamic hormones
 Thyrotrophin releasing hormone (TRH)
 Corticotrophin releasing hormone (CRH)
 Gonadotrphin releasing horm. (GnRH)
 Growth hormone releasing hor .(GHRH)
 ,, ,, inhibitory ,, (GHIH)
also known as somatostatin
 Prolactin inhibitory hormone (PIH)
 Prolactin releasing hormone (PRH)
 .Contd
 Brain  Limbic system

Hypothalamus
 RH or IH
Ant. pituitary
 trophic H
 Negative
Target gland
Feedback
 target gld. hormone
 Posterior pituitary
 Brain & limbic system
 Hypothalamic receptors
electrical signals
 Supraoptic & paraventricular nuclei
(already synthesised ADH &
oxytocin, pass down nerve axons 
Stored in post. Pituitary) 
 Released on arrival of nerve
signals
 Pineal gland

 Small gland attached by a stalk to

posterior commissure of corpus
callosum (often calcified)
 Innervated by β-adrenergic
sympathetic nerves
 From superior cervical ganglion
 Sympathetic neurons in spinal cord
intermedio-lateral columns
 Which receive neurons from
descend-ing neurons from
suprachiasmatic nuclei
 These receive fibres from optic
nerve
 Pineal gland contd.
 Secretion: MELATONIN
 Derived from serotontin (5-HT)
 Found in blood & CSF
 Diurnal rhythm high at night
 During dark hours
 In animals during winter
 Light/dark response explained
by sympathetic connection
 Diurnal (24 hr) rhythm examples

MELATONIN
CRH

CORTISOL TSH

LEPTIN GnRH

LH
 Pineal gland contd.
 Function of melatonin
 Not certain
 Higher in children & young adults
 Decreases with age
 No dramatic change at puberty
 Decreases gonadotrophin production
e.g. in animals before oestrus
 Sometimes inhibitory
 At other times stimulatory
 Adrenal medulla

 Receives direct nerve supply

 From Intermediolateral
neurons of lower thoracic &
lumbar spine i.e.
 Preganglionic sympathetic
 Release acetylecholine
transmitter
 Stimulates chromaffin cells
  release adrenalin &
noradrenalin (hormnes) in blood
 Augment the effects of
sympathetic neural stimulation
 Mass action of sympathetic
 Adrenergic receptors
selective effects of catecholamines
 Alpha 1 rec.:
 Vasoconstriction by noradrenalin
 Alpha 2 rec :
 Vasoconstiction by adrenalin &
noradrenalin
skin, splanchnic vessels, kidney,
systemic veins
 Beta 1 rec. : tachycardia &
increasd myocardial contractility
by both adr. & noradrenalin
 Beta 2 rec.: vasodilation in
muscles by adrenalin.
 Limbic system
hypothalamus

ANS Ant.Pit post. Pit Pineal

Adr. M Trophic H
ETC Stress hormones
 Stress hormones
 ACTH
hypothalamic neural regulation
 Cortisol
anti-insulin effect
FFA mobilization
Gluconeogenesis
CVS potentiation of catecholamines

increases COP, vasoconstriction

Maintenance of BP
 Adrenalin
hypothalamic neural regulation
adrenal medullary hormones
 Glucose homeostasis
 FFA mobilization
 Gluconeogenesis
 Growth hormone
Glucose homeostasis in
absence of exogenous glucose
Postabsotptive state
exercise in Postabsotptive
state FFA mobilisation
inhibition of gluc.
utilization
 Glucagon
glucose homeostasis
FFA mobilization
glycogenolysis
inotropic effect on the heart
increases COP
 Hormonal effects on CNS
 CNS Development
Myelination,
Synapse formation
(cretinism)
 Mentation
 Memory
(myxedema)
 Psychological effects
Sexual behavior
Maternal behavior
nursing behavior during
lactation
 Circadian rhythms
 Hormones of the
anterior pituitary gland
From acidophil cells:
 Growth hormone & prolactin

From basophil cells:

 Thyroid stimulating hormone (TSH) &

Adrenocorticotrophic hormone
(ACTH)
 Lutenizing hormone (LH) & Follicle

syimuating Hormone (FSH)

(Gonadotrophins)
 Growth hormone
Chemistry &degradation:
 Protein - 191 amino acids
 HGH M Wt 21500 D
 SPECIES SPECIFIC
 Half life 20-30 min
 Metabolised in liver
 Growth hormone
 Actions:

1- skeletal
growth

2- metabolic
effects
Bone growth
 Actions contd.
Skeletal growth
 Indirect effect on epiphyseal plate
 Mediated by IGF-I (somatomedin)
from liver when stimulated by GH
 Growth stops when epiphyses close
 Thyroid H & sex Hs also required for
growth
 Actions contd

Metabolic effects
 SECRETION CONTIUES IN ADULTS

GH has Short-term effects on

 CHO,

 FAT

 & PROTEIN METABOLISM

 ACTIONS CONTD.
 CARBOHYDRATE METABOLISM:
 Inhibits peripheral glucose utilisation

 Insulin antagonism

GLUCOSE SPARING (OR COSERVING)

ACTION

 Excess Secretion  Diabetogenic

effect
 ACTIONS CONTD.
FAT METABOLISM
 FFA mobilisation from adipose
tissues
 e.g. In the post absorptive state
 during fasting,& muscular exercise
 Increases FFA oxidation in skeletal
muscle
 Actions contd.
PROTEIN METABLOISM
 GH increases amino acid uptake by
cells
 By increasesing transport
 Increases protein synthesis
 By m-RNA TRANSCRIPTION
 Leads to a positive nitrogen (protein)
balance
 Control of GH secretion
 Secreted normally
 in the postabsorbtive state
e.g 2 hr. after meals & during
fasting
 In Hypoglycaemia
 During Muscular exercise in the
fasting state
 Inresponse to Stess ,physical &
emotional
 Non-REM sleep
 Control contd.
Secretion is inhibited by :
 glucose intake (physiological)

e.g.after meals
 Negative feedback by GH

& IGF-I (somatomedin)

 Cortisol therapy

 FFA
 Abnormalities
Excess secretion in children &
adolescents
GIGANTISM:
 Excessive hieght – PITUITARY
GIANT
diabetes mellitus
 *****
Excess in adults
ACROMEGALLY
 growth of some bones eg Mandible,

face, supra-orbital ridges, hands &

feet
 enlargement of some organs eg

tongue, liver, spleen

 thickening of skin of face

 diabetes mellitus

 abnormal release & suppression

Acromegaly
 GH deficiency
In children
DWARFISM
 SHORT STATURE

 NORMAL MENTAL DEVELOPMENT

 MAY BE DUE TO SOMATOMEDIN

DEFICIENCY(IGF-I, IGFT-II)
 OR GH RECEPTOR ABNORMALITY i.e.

LARON DWARF
 Prolactin
 A single chain polypeptide
 Molecular weight 22 500 dalton
 ½-life = 15 min
 Secreted in bursts or pulses
CONTROL
1. Under continuous INHIBITION by PIH
2. High durig pregnancy & drops rapidy
immediately after birth
3. Bursts of secretion are stimulated during
suckling by stimulation of nipples
 ****
4. Other stimuli include : sleep, stress, &
muscular exercise
These work thro. The hypothalamus
5. TRH (thyrotropin releasing hormone)
also stimulates PRL release
6. PRL short-loop feedback
7. PIH IS DOPAMINE
dopamine blockers such as
chloropromazine stimulates PRL release
bromocryptine stimulates dopamine
receptors inhibition of PRL release
 Actions of PRL
1. Production of milk
although PRL is high during
pregnancy , a small amount of milk
is produced
because PRL action is suppressed by
high oestrogens from the placenta
2. Maintenance of lactation depends on
regular breast feeding  pulsatile
secretion
 ****
3. PRL has an inhibitory effect on the
ovaries during lactation 
suppression of ovarian & menstrual
cycle
this is aphysiological mechanism of
regulation of spacing of pregnancies
4. Maternal behaviour thro. limbic
system
 Abnormalities of PRL secretion
Hyperprolactinaemia
 Due to pituitary tumor
 May consist of acidophil or
chromophobe cells
 Causes infertility in men & women
 May cause galactorrhoea
 Associated with amenorrhoea
The posterior pituitary gland
neurohypophysis
 Posterior pituitary control

 connected with supraoptic &

paraventricular nuclei of
 hypothalamus through
 hypothalamo-hypophseal tracts
 Hormones
 Antidiuretic H (ADH) or Vasopressin
 Oxytocin
 Both nanopeptides (9 amino acids)
 Both available in synthetic form &
used in clinical practice
 Both degraded in liver & kidneys
 ½ life of ADH 5 min
 ½ life of oxytocin 1-4 min
 ANTIDIURETIC HORMONE
 CONTROL
1. An increase in ECF osmotic
pressure
2. A fall in blood volume
3. A fall in arteial blood pressure
4. Pain, trauma,
5. An increased response with age
6. Morphine, nicotine & barbiturates
stimulate release
7. Alcohol inhibits release
Effect of ECF osmotic pressure
 Dehydration due to excess water loss
or inadequate water intake
 Osmotic pressure rise stimulates
OSMORECEPTORS in supraoptic
nucleus of hypothalamus
 Osmoreceptors are sensitive to minute
changes(1%) normal 290 mosm./l
 Impules are gnerated  release of ADH
 Higher osm. pressure trigers sense of
THIRST also thro hypothalamus
 Effect of blood volume
 Dehydration or haemorrhage
 Compesatory ( CVS) mechanisms
maintain the arterial blood pressure
 But the central venous pressure is
low
 Volume receptors in the rt. Atrium &
great veins near the heart
 believed to send impulses thro vagus
to mudulla hypothalamusADH
secretion
 Response is fast & strong
 Effect of arterial BP
 Baroreceptors are respond when
arteial BP falls  ADH (vasopressin)
 This the most potent stimulus after
haemorrhage resulting in high levels
of thehomone
 Vasopressin has a strong vaso-
constrictor effect
 Acts on V1 receptors
 ACTIONS OF ADH
1. Reabsoption of water in collecting
ducts
 Acts on V2 receptors

  Camp

 Insretion of water channels

(AQUAPORINS) in the luminal

membrane of the collecting ducts
 Water passes quickly out of the cells due

to high osmotic pressure in renal medulla

 Water is reabsorbed into the blood & the

urine becomes more concentrated

 ****
2. Absorption of urea
 Reabsorption of urea also helps

reabsorption of water
3. ADH decreases blood flow in renal
medulla
 This effect maintains the mrdullary

hyper-osmolarity
4. Vasoconstriction
 Amounts higher than normal

physiological levels  vaso-constriction

 Doubtful significance in normal short-

term regulation of BP
 ABNORMALITIES
ADH deficiency  DIABETES INSIPIDUS
 Due to a lesion in hypothalamus

 Large volume of dilute urine

 Exess thirst & drinking

 Removal of post. Pituitary temporary

attack
EXCESS AFTER SURGERY, TRAUMA & IN
PATIENTS WITH CONGESTIVE HF
 Inappropriate release ,  water retention
 OXYTOCIN
Control
(1) Suckling : milk ejection
 stimulation of nipples touch receptors 

afferent pathway
 Hypothalaus signals to post. Pit.

 Release of oxytocin

 Other touch stimuli e.g. clothes

AN EXAMPLE OF A NEURO HORMONAL

REFLEX
 ****
(2) DISTENTION OF UTERUS & stretch
of cervix
 During childbirth  uterine

contractions
 Gradual increase of oxytocin release

 Gradual increase of contractions

 Also neuro-hormonal
 ****
(3) Stimulation of the vagina during
sexual intercourse
 Released at time of female orgasm

 Thought to help passage of sperm up

to fallopian tubes?
 May also result in milk ejection in

lactating mothers
 ****
(4)Inhibitory factors
 Fear

 Anxiety

 Pain

 Work tho.Sympathoadrenal

stimulation
 Alcohol
 BREAST TISSUES
 NOTE:
 LOBULES(ALEOLA
R TISSUE)
 DUCTSNIPPLE
 MILK WITHIN
ALVEOLUS
 ALVEOLAR
EPITHELIUM
 MYOEPITHELIAL
CELLS
 ACTIONS OF OXYTOCIN
(1) EJECTION OF MILk

 Acts on myo-epithelial cells during

suckling
 Squeezes milk already formed
Normal presentation of foetus
 ****
 ACTIONS ON THE UTERUS
 Does not initiate labour
 During late pregnancy there are
infrequent contractions
 The uterus becomes more
sensitive to oxytocin
 Due to falling progesterons levels
 Oxytocin therapy is used to
induce labour
Stages of labour
 Actions contd.
 Oxytocin starts to be released in
increasing amounts
 by distention of uterus & stretch
of cervix by the advancing head
 Leading to taking up of cervix
 Full dilatation
 smooth progress of the three
stages of labour