Transcript Biol 155 Human Physiology - Department of Zoology, UBC

Pituitary Gland
Pituitary development:
The “Master Gland”

The pituitary has been
called the “Master” gland
in the body.

This is because most of
the pituitary hormones
control other endocrine
glands
Hormones of the anterior pituitary

There are 6 main hormones which are secreted by the
adenohypophysis:

1) Growth hormone (also known as somatotropin).

2) Thyroid-stimulating hormone (also known as thyrotropin).

3) Adrenocorticotropic hormone (also known as corticotropin).

4) Prolactin.

5) Follicle-stimulating hormone.

6) Luteinizing hormone.
Control of pituitary gland secretion


Secretion of each hormone by the
adenohypophysis is controlled by
neurohormones secreted by nerves in the
hypothalamus.
In most cases there are two neurohormones
controlling the secretion of a pituitary hormone.
One which stimulates pituitary secretion and one
which inhibits pituitary secretion.
Neurohormones:



Are hormones secreted by nerve cells. These
are true hormones, since they are secreted into
the bloodstream.
All are secreted by neurosecretory neurons in
the hypothalamus.
They are secreted into the hypophyseal portal
system, which then carries the blood to the
anterior pituitary.
Pituitary portal system




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Arterioles break into capillaries in the hypothalamus.
The axons of the neurosecretory cells form plexuses
with these capillaries.
Downstream, the capillaries combine into a vein which
carries the blood to the pars distalis.
The vein breaks into a capillary network which supplies
all the cells of the anterior lobe.
Thus, the neurohormones are carried directly (well, sort
of) from the hypothalamus to the adenohypophysis.
Portal system
Growth hormone (GH)

Growth hormone is secreted by somatotrophs.

GH is a protein hormone consisting of a single peptide chain of
191 amino acids.

GH secretion is stimulated by the secretion of Growth Hormone
Releasing Hormone (GHRH) by the hypothalamus.

GH secretion is inhibited by the secretion of somatostatin by the
hypothalamus.

GH activates a tyrosine kinase receptor.
Functions of GH:

GH has effects of every cell of the body, either directly
or indirectly. Primarily, it decreases the uptake and
metabolism of glucose. (Elevates plasma glucose)

Increases the breakdown of fat. (Increases the blood
levels of fatty acids)

Increases the uptake of amino acids from the blood
and increases protein synthesis in cell. (Decreases
plasma amino acids)
Actions of GH on specific cell types:

Muscle cells:
Increases amino acid uptake
 Increases protein synthesis
 Decreases glucose uptake


Net result: Increased Lean body mass

Chondrocytes:
Increases uptake of sulfur
 increases chondroitin sulfate production
 increases DNA, RNA synthesis
 increases Protein synthesis
 increases Amino acid uptake
 increases Collagen synthesis
 increases Cell size and number


Net result: Increased Linear growth

Hepatocytes:

Stimulates the production of somatomedins by the
liver.

These somatomedins directly regulate metabolic
function in target cells. They are also called insulinlike growth factors, or IGFs.

Adipocytes:
Decreases glucose uptake
 Increases lypolysis


Net result: Decreased Adiposity

Other cell types in general:
Increased protein synthesis
 Increased DNA, RNA synthesis
 Increased cell size and number


Net result: Increased organ size
Increased organ function
Other considerations:

GH has a short half-life of about 20 minutes.
However, the IGFs are much longer lived (T1/2
of about 20 hours).
GH and Insulin actions are correlated:

When there is ample dietary intake of proteins and carbohydrates,
then amino acids can be used for protein synthesis and growth.

Under these conditions, both insulin and GH secretion are
stimulated.

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Net result: Amino acids are shunted to protein synthesis and glucose is shunted
to metabolism.
However, under conditions where only carbohydrates are ingested,
insulin secretion is increased, but GH secretion is decreased.

Net result: Both glucose AND amino acids are shunted to metabolism.
Pathophysiology of abnormal GH
secretion:

Hyposecretion:

Pre-adolescents:


Decreased GH secretion (or sensitivity) results in slow
growth and delayed onset of sexual maturation. These
children also tend to be slightly chubby.
Post-adolescents:

Generally, no serious problems are associated with
hyposecretion of GH in mature individuals. However, in
very severe cases there can be progeria (rapid and
premature aging).
Hypersecretion:

Pre-adolescents: (before closure of
epiphyseal plates)

Hypersecretion results in gigantism, where
affected individuals grow extremely rapidly and
become abnormally tall (even over 2.4 m). Body
proportions remain relatively normal. Usually,
there are cardiovascular complications later in
life.

Post- adolescents: (after epiphyseal closure).

Hypersecretion results in tissue enlargement.
This is particularly true of the bones, which get
heavier and thicker. They cannot elongate since
the epiphyseal plates are closed. A common
symptom is a coarsening of the facial features
and enlargement of the hands and feet. This
condition is known as acromegaly.
Treatments of GH secretion disorders:

Hypersecretion is usually caused by a tumour in
the pituitary gland. Treatment consists of
surgical or radiation ablation of the tumour
mass.

Hyposecretion is usually treated in children by
hormone replacement therapy. This is generally
not required in adults, unless GH secretion is
completely abolished.
Prolactin (PRL)

Structurally, very similar to growth hormone
(single peptide chain of 198 amino acids).

PRL is secreted by mammotrophs (also referred
to as lactotrophs).

Secretion of PRL is also under dual control by
the hypothalamus.

Primarily under inhibitory control. This means that if
there is an injury to the hypophyseal portal system
which blocks hypothalamic regulation of the pituitary
gland, PRL levels increase. All other pituitary hormone
levels decrease when this happens.

Dopamine is secreted by neuroendocrine cells in the
hypothalamus and inhibits PRL release.

PRL release is stimulated by thyrotropin releasing
hormone (TRH), vasoactive intestinal peptide (VIP)
and at least one other as yet unidentified factor.

PRL activates a tyrosine kinase receptor.
Functions of PRL:

In humans, the only effects of PRL so far
identified are on reproduction and nursing.

PRL is important in stimulating differentiation of
breast tissue during development.

Stimulates further development of mammary
glands during pregnancy.

Stimulates milk production (lactation) after pregnancy.

PRL has a role in regulation of the female reproductive
cycle. However, its precise role has not be delineated
yet. Excess PRL secretion is know to block synthesis
and release of gonadotropins, disrupting menstruation
and causing infertility.

PRL also can regulate male fertility, but how it does so
remains unclear.
Pathophysiology of PRL secretion:

Hyposecretion is never seen. However,
hyperprolactinemia (excess secretion of PRL) is
a fairly common disorder. Symptoms in women
usually include amenorrhea (cessation of
menstruation), galactorrhea (abnormal lactation)
and infertility. In men, infertility and
galactorrhea are the most common symptoms.

Treatment usually consists of administration of
a dopaminergic agonist, such as bromocriptine.
Cellular mechanism of pulsatile LHRH release. 1998. E. Terasawa.
General and Comparative Endocrinology. vol. 112:283-295
Thyroid Stimulating hormone (TSH)

TSH is a glycoprotein hormone composed of 2
peptide chains a and b.

The a subunit is called “unspecific” because it is
also incorporated into two other unrelated
pituitary hormones (LH and FSH).

The b subunit contains the biologically active
sites. However, it must be combined with the a
subunit in order for the hormone to be active.

TSH secretion is controlled very tightly by the
hypothalamus.

TSH secretion is stimulated by Thyrotropinreleasing hormone (TRH). TRH is a tripeptide,
meaning it is composed of three amino acids.

TRH secretion is stimulated by thermal and
caloric signals in the brain.
Control of TSH secretion

Negative control of TSH secretion occurs in
two ways:

Triiodothyronien or T3 (which will be discussed
later) feeds back on the hypothalamus to stimulate
secretion of dopamine and somatostatin. These two
factors both function as TSH-release inhibiting
factors.

T3 can feed back directly onto the thyrotrophs to
directly inhibit TSH secretion.
Function of TSH:

TSH stimulates the follicular cells of the thyroid
to induce a number of responses:

TSH activates both the cAMP and PIP pathways:


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Increased cAMP
Increased [Ca2+]i
TSH can stimulate both cell growth (of
follicular cells) and secretion of T3 and
thyroxine ( T4 ).
Adrenocorticotropic hormone (ACTH)

ACTH is a single peptide chain which is
relatively small (30 amino acids).

ACTH secretion is primarily under stimulatory
control (i.e. there isn’t an ACTH-release
inhibitory factor).

ACTH secretion is stimulated by corticotropin
releasing hormone (CRH).

CRH secretion can be stimulated by a large
number of factors, most of which would be
considered stress factors.

Examples; infection, trauma, sleep cycle, anxiety,
depression and others. (Just remember stress).
Functions of ACTH:

ACTH stimulates the adrenal gland to secrete cortisol.

ACTH levels are associated with the sleep cycle.

ACTH stimulates the cAMP pathway in adrenocorticol
cells.

ACTH can directly inhibit CRH secretion (negative
feedback).
Follicular-Stimulating hormone (FSH)
Luteinizing Hormone (LH)

These are generally grouped together and called gonadotropines.

Gonadotropins are secreted by the gonadotrophs, which
synthesize and secrete both LH and FSH.

Both LH and FSH are peptide hormones.

Secretion of gonadotropins is mainly under positive control.

Hypothalamus secretes gonadotropin-releasing hormone
(GnRH) which stimulates gonadotrophs to secrete both LH and
FSH.
Functions of LH and FSH:

LH and FSH stimulate secretion of the sex steroids by the
gonads. Mainly estrogen in women and testosterone in men.

FSH also stimulates gonadal release of inhibin, which serves as a
negative feedback factor to block release of FSH by pituitary.

LH and FSH stimulate the gonadal release of activin, which can
have positive feedback on gonadotropin secretion by the
pituitary.

Gonadal secretion of estrogen and testosterone can negatively
feedback on both the hypothalamus, to reduce GnRH secretion,
and the gonadotrophs directly, to reduce gonadotropin
secretions.
Hormones of the posterior
pituitary:

Remember that the neurohypophysis serves as a storage organ
for hormones produced by neurosecretory cells in the
hypothalamus.

There are two hormones secreted by the neurohypophysis:

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1) antidiuretic hormone (ADH)
2) oxytocin

Both hormones are peptide hormones containing 9 amino acid
residues.

They differ in only 2 amino acids, but have very different
functions.
ADH

Term: diuresis means production of urine.

ADH inhibits urine production, i.e. conserves water in the body.

Main target for ADH are the cells in the kidney which reabsorb
water (will be covered in detail in the section on renal
physiology).

ADH secretion is stimulated by either an increase in the osmotic
concentration of the blood, or by a decrease in blood volume

usually sensed by a decrease in blood pressure.

Secretion of ADH causes retention of water, which will tend to
counteract both an increase in blood concentration and/or
decrease in blood volume.

Cannot overcome serious blood loss.

Conversely, excess consumption of water will have two effects:


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increase blood volume (and pressure).
decrease blood concentration.
Under these conditions ADH secretion is inhibited.

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This results in formation of more urine, which is usually fairly dilute.
Blood loses water and thus volume.
Oxytocin

Release of oxytocin is under neural control (like
with ADH).

However, unlike ADH, the release of oxytocin is
largely controlled by emotional state.

Oxytocin specifically stimulates certain smooth
muscles to contract.

Primarily those of the reproductive tract and mammary
glands.

Oxytocin is required for nursing.

Principally know as the “milk letdown factor”.

It is secreted within seconds of the onset of
suckling.
Sensory receptors in the nipples generate afferent
impulses that stimulate the hypothalamus, triggering
oxytocin secretion.
 Can actually be secreted in response to auditory input, i.e.
in nursing mothers in response to hearing their babies
cry.

Effects of Oxytocin

Oxytocin stimulation at low doses causes
rhythmic contractions of the uterus.

Oxytocin stimulation at high dose causes
sustained tetanic uterine contractions.

Oxytocin is often used to induce labour.

It is now generally believed that oxytocin believed that
oxytocin produced by the fetus plays a critical role in
labour.

Oxytocin is also used to stop post-partum bleeding.

The number of oxytocin receptors in uterine smooth
muscles increases towards the end of pregnancy.

Oxytocin affects smooth muscle cells in uterus and
vagina of non-pregnant women.

There is clear evidence that oxytocin is involved in
sexual arousal and orgasm in both men and women.
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What role it plays in men is unknown. However, it may play
a strong role in reinforcing the pair-bond.
The role in women is only slightly better known.
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Oxytocin is secreted in response to vaginal distention during
intercourse.
Oxytocin is also secreted in response to stimulation of the
nipples.
Emotional considerations

Oxytocin secretion during sexual intercourse
probably serves to reinforce the male-female
pair-bond.

Often referred to as the “the cuddle hormone” or
“the love hormone” in the popular press.

Secretion of oxytocin during and after labour
may play an important role in the formation of
the mother-child pair-bond.

Oxytocin secreted during suckling may serve to
reinforce this pair-bond.

Recent studies with knock out mice has shown
that oxytocin is critical in initiating and
maintaining maternal care.

Oxytocin secreted in response to suckling can cause
uterine contractions which may play a role in the
recovery of uterine muscle tone after pregnancy and
may serve to shrink the uterus back to normal.
Pituitary evolution
Teleost Pituitary
Bichir (Paleonisci)
Sturgeon (Ascipenseridae)
Bowfin (Amiformes)
Gar (Amiformes)
Bass (Teleostei)
Sarcopterygii (Fleshy finned fishes)

Made up of two extant groups:

Dipnoi
Lungfish

Crossopterygii
Lobe finned fishes
Coelacanths
Lungfish (Dipnoi)
Ceolocant (Crossopterygii)
Fire Salamander (Urodel)
Bullfrog (Anuran)
Lizards and snakes (Squamata)
Albatross (Aves)