Introduction to HPA

pathway – and other

hypothalamic and
pituitary hormones

2nd Year Physiology

Dr. Tara Speranza
Physiology, School of Medical Sciences
tara.speranza@sydney.edu.au

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 Lecture Summary

– Central Endocrine Glands

– Hypothalamus and hypothalamic hormones
– Pituitary gland
– Posterior pituitary and posterior pituitary hormones
– Anterior pituitary and anterior pituitary hormones
– Hypothalamic-hypophyseal portal system
– Prolactin (PRL)
– Adrenocorticotropic hormone (ACTH) and cortisol (HPA
Pathway)
– Adrenal Gland and adrenal hormones
– Actions of cortisol
– Gonadotropes (FSH and LH)
– Growth Hormone

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 Central Endocrine Glands
– Those within or in close association with the
brain

– Hypothalamus
– Pituitary gland
– Pineal gland

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The hypothalamus and pituitary gland
– Connected by a thin stalk - infundibulum
– Pituitary gland is actually TWO separate tissue types
– Merged during embryonic development
– Anterior and Posterior pituitary gland

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 Hypothalamic hormones

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 Pituitary gland
Anterior pituitary Posterior pituitary
– “True” endocrine gland – Extension of neural
– Aka adenohypophysis tissue
– Aka neurohypophysis
– Secretes hormones
made by the
hypothalamus

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 Neurosecretory Neurons
– Two specific cell bodies lie within the hypothalamus

• Supraoptic neucleus

• Paraventricular nucleus

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 Posterior pituitary
– Two hormones are released
– Vasopressin (Antidiuretic
hormone; ADH)
– Oxytocin
– Both are synthesised by
neuronal cell bodies in the
hypothalamus

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 Anterior pituitary
– In contrast to the posterior pituitary, hormones are
produced and secreted from the anterior pituitary
– BUT are under the direct control of hypothalamic
hormones

– Hormones released from the hypothalamus travel

via a specialised portal system to the anterior
pituitary
– Prevents “dilution”

– Hypothalamic-hypophyseal portal system

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 Hypothalamic-hypophyseal portal system

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 Hypothalamic hormones
– The release of hormone from the anterior pituitary is
controlled by hypothalamic hormones (neurohormones)
– Contain both inhibiting and releasing hormones

– Their release is controlled by a variety of neural and

hormonal inputs to neurosecretory cells of the
hypothalamus
Dopamine (PIH)
Thyrotropin-releasing hormone (TRH)
Corticotropin-releasing hormone (CRH)
Growth hormone-releasing hormone (GHRH)
Somatostatin (GHIH)
Gonadotropin-releasing hormone (GnRH)

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Prolactin-releasing peptide (PrRP) Page 11
 Anterior pituitary hormones

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 Anterior pituitary hormones
– Feedback loops of anterior
pituitary hormones

– Hormones themselves are the

feedback signal
– Dominant form is long-loop
negative feedback
– Some show short-loop negative
feedback

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 Prolactin (PRL)
– Only anterior pituitary hormone
that is not a tropic hormone
– Acts directly on breast tissue
– Controls milk production
(lactation) in breast tissue and
enhances breast development
– Primarily controlled by dopamine
– Decreases as pregnancy advances
– Shares a similar structure to GH
– Role in males is uncertain but
shown to have a role in the
immune system
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 Adrenocorticotropic hormone (ACTH)
and cortisol
– Acts on adrenal cortex to promote the
synthesis and release of cortisol

– Cortisol has a strong negative

feedback effect on the anterior
pituitary to inhibit ACTH secretion

– Cortisol is essential for life and has a

key role in preventing hypoglycaemia

– Cortisol allows glucagon to respond to

a hypoglycaemic event (permissive
effect)
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 Abnormal cortisol secretion
– Hypercortisolism
– Tumors of adrenal gland or pituitary
– Exogenous administration
– Cushing’s syndrome

– Hypocortisolism
– Not as common
– Addison’s disease
– Congenital adrenal hyperplasia

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 The Adrenal Gland

• Anatomy of the adrenal gland

• Functions of the adrenal medulla
• Functions of the adrenal cortex
• Stress and the adrenal gland
• What is stress?
• Acute stress, “flight or fight”
• Chronic stress
• The pathology of stress

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 Anatomy of the adrenal gland

Figure 23-1b

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Figure 23.1a-3 (4 of 5)

Region Secretes
Capsule
Capsule

Zona Aldosterone
glomerulosa
Adrenal cortex
secretes steroid
hormones.

Zona Glucocorticoids
fasciculata

Zona
reticularis Sex hormones

Adrenal
medulla Catecholamines
Adrenal medulla
secretes catecholamines.

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Figure 23-1c
 Functions of the adrenal medulla

• Part of the Sympathetic nervous system

• Medulla is modified sympathetic ganglion
• Responds to stimulation of the sympathetic
nervous system
• Releases Adrenalin (epinephrine) into the
bloodstream

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 Adrenal Medulla

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Figure 11-10c
 Functions of the adrenal cortex

• Three anatomical zones secreting different steroid

hormones
• Zona reticularis: sex steroids mostly androgens,
especially Dehydroepiandrosterone (DHEA)
• Zona fasciculata: glucocorticoids
• Zona glomerulosa: mineralocorticoids

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Figure 23.1a-3 (4 of 5)

Region Secretes
Capsule
Capsule

Zona Aldosterone
glomerulosa
Adrenal cortex
secretes steroid
hormones.

Zona Glucocorticoids
fasciculata

Zona
reticularis Sex hormones

Adrenal
medulla Catecholamines
Adrenal medulla
secretes catecholamines.

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Figure 23-1c
 Pregnenolone 17α-hydroxy-
Pregnenolone

17α-hydroxy-
Progesterone

11-deoxy- 11-deoxycortisol
corticosterone

11β-hydroxylase 11β-hydroxylase

Aldosterone
Generalised steroid pathway
synthesase

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Figure 23-2
 Functions of the adrenal cortex

• Zona glomerulosa produces aldosterone

• The specific production of aldosterone only occurs in the
Zona glomerulosa
• Acts on the distal tubule of the kidney to retain salt and
water
• Activated by renin-angiotensin system in response to
dehydration.

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 Functions of the adrenal cortex
• Zona fasciculata produces cortisol
• Cortisol is a glucocorticoid, that is it promotes the formation of
new glucose.
• Corticosterone is also a glucocorticoid and is the main one in many
species
• Cortisol – humans (and other primates) dogs (and other canids),
marsupials and fish
• Corticosterone – birds, many rodents, reptiles and amphibians.

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 The Hypothalamic-Pituitary-Adrenal pathway for the control of
cortisol secretion

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Figure 23-3
 Pregnenolone 17α-hydroxy-
Pregnenolone

17α-hydroxy-
Progesterone

11-deoxy- 11-deoxycortisol
corticosterone

11β-hydroxylase 11β-hydroxylase

Aldosterone
Zona fasciculata pathway
synthesase

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Figure 23-2
 – Actions of cortisol

1. Carbohydrate metabolism – glucocorticoid hormone

(i) Liver: gluconeogenesis & glycogen synthesis (for later use)
↑ protein synthesis of required enzymes
necessary amino acids from protein
catabolism in muscle & skin
(ii) ↓ rate of glucose utilization by cells such as
muscle and adipose tissue
= anti-insulin action producing insulin resistance
↓ NADH oxidation
↓ transport of glucose into muscle and Adipose Tissue i.e.
↓ peripheral utilization of glucose

(iii) ↑ glucose in blood due to (i) and (ii), and ↑ glucose- 6-

phosphatase (reverses insulin action on hexokinase)

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 – Actions of cortisol
– 2. Protein metabolism
(i) Liver: ↑ protein enzyme synthesis
↑ amino acid transport in
(ii) In other cells: ↓ protein in cell
↓ amino acid transport in
↓ protein synthesis
↑ protein catabolism

3. Fat metabolism
↑ lipolysis (in adipose tissue)
↑ free Fatty acids, glycerol (to liver for gluconeogenesis)
NB deposition of fat in abdomen in cortisol excess is due to
differential actions on peripheral and central tissues

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 – Actions of cortisol

– 4. Vascular reactivity
Cortisol induces ↑ responsiveness of blood vessels to
catecholamines, angiotensin, etc i.e. “permissive effect”
for vasoconstriction

– 5. Immunosuppressive & anti-inflammatory activity

Cortisol suppresses both immune and inflammatory
responses

6. Permissive effect for normoglycemia

Cortisol is necessary for glucagon to produce glucose (as
well as doing this itself)

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 * ACTIONS OF *
Gluconeogenesis ↑ GLUCOCORTICOIDS

enzyme
synthesis ↑ LIVER
↑ GLYCEROL
FATTY ACIDS
GLUCOSE

↑AMINO ACIDS

protein  To heart &

brain
MUSCLE
ADIPOSE TISSUE
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 Gonadotropes (FSH and LH)
– Controlled by GnRH from hypothalamus and act on the gonads
(both males and females)
– FSH:
– Promotes gametogenesis
– LH:
– Stimulates the production of sex steroids

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 Growth hormone
– Most abundant anterior pituitary hormone produced

– Released throughout life

– Dominant role in children
– Peaks during teenage years
– Decreases around middle-age

– Stimuli for release include:

– Circulating nutrients
– Stress
– Other hormones

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 Growth hormone

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 Control of GH release
– Influenced by two hypothalamic hormones:
– GHRH and GHIH (somatostatin)

– Triggered for release by a range of factors:

– Diurnal pattern
– Exercise
– Stress
– Low glucose (major stimuli)

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 GH metabolic effects
– Binds directly with target organs:
– Adipose tissue
– Skeletal muscle
– Liver

– Increases fatty acid levels by breaking down stored fat

– Increases blood glucose by decreasing skeletal muscle
glucose uptake

– Promotes glucose output from the liver

– Stimulates protein synthesis
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 GH effects on growth
– Indirect effect on cell division, increased protein synthesis
and bone growth

– Directly mediated by insulin-like growth factors (IGFs)

– Act on soft tissues and bone to promote growth
– Two types: IGF-I and IGF-II

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 Learning outcomes
- to understand the functions of:
– Central Endocrine Glands
– Hypothalamus and hypothalamic hormones
– Pituitary gland
– Posterior pituitary and posterior pituitary hormones
– Anterior pituitary and anterior pituitary hormones
– Hypothalamic-hypophyseal portal system
– Prolactin (PRL)
– Adrenocorticotropic hormone (ACTH) and cortisol (HPA
Pathway)
– Adrenal Gland and adrenal hormones
– Actions of cortisol
– Gonadotropes (FSH and LH)
– Growth Hormone

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