Bicol University College of Medicine

Doctor of Medicine - Masters in Public Administration

Integrated Basic Sciences

Subject:

Lecturer:
Facilitator:

Dr. Edberto General, MD

Dr. Virgilio Ludovice, MD

Title:
Endocrinology (Introduction & Pituitary Gland)
nd
TRANS HEAD:
MARAVILLAS, Micah James S.
Sem/ A.Y.:
2 /A.Y. 2014-2015
Transcribers: ABANO, P., BRON, J., GARAY, M., MARAVILLAS, J., OLIVERA, T., TABLIZO, K., ZEPEDA, K.

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OUTLINE
ENDOCRINOLOGY
Principal Endocrine Organs And Tissues Of The Body
Three General Classes Of Hormones
Transport and Clearance of Hormones in the Blood
The Pituitary Gland
Formation of the Pituitary Gland
Anterior and Posterior Pituitary Gland
Hypothalamic-Hypophyseal Portal Blood Vessels in the
Anterior Pituitary Gland
Major Cell Types of the Anterior Pituitary Gland and Their
Major Functions
Hormones of the Anterior Pituitary Gland
Hormones of the Posterior Pituitary Gland
Growth Hormones and Their Metabolic Effects
Growth Hormones Stimulation of Cartilage and Bone
Growth
Regulation of growth Hormone Secretion
Abnormalities of Growth Hormone Secretion
ADH and its Physiological Functions
Regulation of ADH Production
OBJECTIVES
To be able to discuss and know the principal endocrine organs
and its functions
To be able to describe the pituitary gland and discuss the
hormones secreted
Discuss the growth hormone and its metabolic effects
Discuss the importance of ADH and its functions
Know the differential growth hormone abnormalities

a)
b)
c)
d)
e)
f)
g)

These hormones are released in to the circulating blood and

affect or influence the function of cells at another location in
the body
The endocrine system is essential for cell-to-cell
communication and also for maintenance of the following
functions:
Food seeking and satiety
Metabolism and caloric economy
Growth and differentiation
Reproduction
Homeostasis
Response to environmental change
Arousal, defense, flight, and secluding behaviors.

COMPONENT ORGANS OF THE ENDOCRINE SYSTEM

a.
b.
c.
d.
e.
f.
g.
h.
i.
j.
k.

Pituitary Gland
Adrenals
Thyroid Gland
Parathyroid Gland
Pineal Gland
Thymus
Pancreas
Kidneys
Testis
Ovaries
Placenta

ENDOCRINOLOGY (INTRODUCTION AND PITUITARY GLAND)

ENDOCRINOLOGY
DEFINITION

Study of processes involved in the regulation and integration

of cells and organ systems by hormones
HORMONE

Chemical substance secreted by one group of cells with

effects or control on other cells

Exert their effects by binding to specific receptors in the cells

of the target organ.
ENDOCRINE GLAND

Ductless

Highly vascularized for efficient and fast distribution of

hormones into the blood stream and their target organs

Generally contain epithelial cells arranged in chords

Secretion is INWARD

It is a tissue that produces chemical substances called

hormones
FIGURE 1:Human Body Showing Some of the Important
Component Organs of the Endocrine System
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ENDOCRINE
SYSTEM

CLASSES OF HORMONES
1)
2)
3)

PEPTIDES
STEROIDS
AMINO ACID DERIVATIVES
o
Function like steroids
o
Function like peptides
PEPTIDE HORMONES

Water soluble
HYDROPHILIC in nature
When secreted in plasma, it blends well with water
containing blood

No specific transport mechanism

THEY ARE NOT BOUND TO PLASMA PROTEINS
WHILE THEY ARE BEING TRANSPORTED IN
THE BLOODSTREAM!!!
Major predominant form is in the FREE FORM.
Very few are bound to a carrier protein eg. GH and
IGF-1

Act by binding to receptors on the CELL MEMBRANE

SURFACE (integral protein) because of the hydrophilic
nature

Synthesized as larger precursors in the RER first and then

stored in secretory vesicles within endocrine cells.

NEED SECOND MESSENGERS (amplifies transmitted

signals) to exert their action.

SECRETORY PEPTIDES

Exemplefied by:
PITUITARY HORMONES Pituitary Gland
HYPOTHALAMIC HORMONES Hypothalamus
INSULIN AND GLUCAGON Endocrine Pancreas
PTH Parathyroid Hormones

Onset of effect is FAST but easily degraded by PEPTIDASES

therefore the duration of action is SHORT.
STEROID HORMONES

LIPOPHILIC
o
Easily diffuse across cell membrane
o
Exert their effects by binding to receptors found at
the CYTOPLASM or NUCLEUS
o
Needs carrier protein

Precursor
o
CHOLESTEROL most steroid hormones
o
7-dehydrocholesterol vitamin D metabolites

BOUND TO PLASMA PROTEINS

o
Eg. Testosterone and Estrogen

Bound to SHBG or Sex Hormone Binding

Globulin
o
MAJOR PREDOMINANT FORM = PROTEIN
BOUND

Synthesized in SER

NO STORAGE FORM for any steroid hormone

o
Meaning they have to be synthesized first
whenever needed.

Affects gene expression; increase of decrease synthesis of

key regulatory proteins of the cell. Hence, onset of action for
the majority is relatively slower than peptides. Duration of
effects is longer.

GONADS - Androgen, Estrogen, Progestin

ADRENAL CORTEX Glucocorticoids, Mineralocoticoids

o
THYROID HORMONES in the thyroid gand
Lipid soluble and interact with intracellular nuclear receptors

Function like PEPTIDES

o
Dopamine, Epinephrine, and Norepinephrine

Secreted by adrenal medulla and nerves

Interact with cell membrane surface

receptors

ALL AMINO ACID DERIVATIVES ARE SYNTHESIZED IN

THE CYTOPLASM
ALL AMINO ACID DERIVATIVES HAVE A STORAGE FORM
(THYROID FOLLICLES)

TWO TYPES OF HORMONES IN THE PLASMA

FREE FORM

Biologically active

For a hormone to interact with the receptor, it has to be in this

form!
BOUND FORM

Bound to a cerrier or transport protein

Will only interact with the receptor once it is liberated from the
transport protein

Binding to a carrier protein extends half life of the

hormone. If it is secreted, bound form will not be degraded
since it is still bound to a carrier or trnasport protein.

Since steroids are greatly bound in the plasma, they have

LONGER HALF LIVES because they serve as reservoir in the
plasma

RECAP!!! (Added notes form Dr. Generals Lecture)

AMINO ACID DERIVATIVES
Dopamine
Catecholamine
Thyroid Hormone
SMALL NEUROPEPTIDES
GnRH
TRH
Somatostatin
Vasopressin (ADH)
LARGE PROTEINS
Insulin
LH
PTH
-produced by classic endocrine glands
STEROID
Cortisol
Estrogen
-cholesterol based precursors
VITAMIN DERIVATIVES
Retinoids (vit.A)
Vitamin D

AMINO ACID DERIVATIVES

Derived form TYROSINE or TRYPTOPHAN

Function like STEROIDS

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ENDOCRINE
SYSTEM

PITUITARY GLAND / HYPOPHYSIS

DIVISIONS OF THE PITUITARY GLAND

ANTERIOR PITUITARY GLAND or ADENOHYPOPHYSIS

Has the characteristics of an ENDOCRINE GLAND

PARS DISTALIS largest, anterior portion

PARS TUBERALIS hugs/enclose the stalk

PARS INTERMEDIA in between adenohypophysis and

neurohypophysis

FIGURE 2: Pituitary Gland. Coronal Section of the Brain.

GROSS ANATOMY

Lies in a cavity of the sphenoid bone known as the SELLA

TURCICA and ventral to the diaphragm sella.

INFUNDIBULUM connects the Pituitary Gland to the

Hypothalamus (responsible for NEUROENDOCRINE
CONTROL inhibitory or stimulatory)

Regulated by the endocrine functions of the hypothalamus

0.5g in males and 1.5g in multiparous females

o
600mg on average

Diameter: 10x13x16m

Divided in ANTERIOR and POSTERIOR LOBES

Anatomical Relations:
o
OPTIC CHIASM first affected in enlarged
Pituitary
o
Internal Carotid Artery
o
CN III (Oculomotor)
o
CN IV (Trochlear)

BLOOD SUPPLY: Superior and Inferior Hypophyseal arteries

o
HYPOTHALAMIC

Comes from the PITUITARY PORTAL

PLEXUS major blood source for the
ANTERIOR PITUITARY GLAND

INFERIOR HYPOPHYSEAL ARTERIES

major blood source for the posterior
pituitary gland

POSTERIOR PITUITARY GLAND or NEUROHYPOPHYSIS

Has the characteristics of a BRAIN TISSUE

INFUNDIBULUM bridges hypothalamic and hypopheseal

systems

PARS NERVOSA majority of the posterior pituitary gland

and is the storage site of OXYTOCIN and VASOPRESSIN
(ADH)

FIGURE 3: Divisions of the Pituitary Gland

NEUROVASCULAR SYSTEMS
1)

EMBRYOLOGY OF THE PITUITARY GLAND

ADENOHYPOPHYSIS / ANTERIOR PITUITARY GLAND

Initially arise from the ORAL ECTODERM

Rathkes Pouch / Hypophyseal Pouch

o
Cranially outpouching from the oral ectoderm that
develops during the second month.
o
Cells of the ANTERIOR wall of this pouch will
proliferate and form the PARS ANTERIOR.
o
ORAL ECTODERM AND RATHKES POUCH can
both be the embryonic origin of the Anterior
Pituitary Gland
NEUROHYPOPHYSIS / POSTERIOR PITUITARY GLAND

Arises form the floor of the DIENCEPHALON

INFUNDIBULUM grows caudally or inferiorly from the floor

of the diencephalon to differentiate into STALK/PARS
NERVOSA of the pituitary gland.

2)

BLOOD SUPPLY

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Hypothalamo-Hypophyseal Portal System (VASCULAR)

ONLY IN ANTERIOR PITUITARY GLAND

From the hypothalamus to the anterior pituitary gland

Carries neuropeptides form the median eminence to the

adenohypophysis where they either stimulate or inhibit
hormone release of the anterior pituitary endocrine cells.
Hypothalamic/Hypophyseal Tract (AXONS)

Transverses the neurohypophysis

Its axons branch form the PARAVENTRICULAR and

SUPRAOPTIC nuclei which secrete oxytocin and ADH.

INTERNAL CAROTID ARTERY

o
Superior Hypophyseal Artery

Pars tuberalis

Infundibular Stalk

Median Eminence
o
Inferior Hypophyseal Artery

Posterior Pituitary Gland

Stalk
Drained by the HYPOPHYSEAL VEIN

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ENDOCRINE
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Regulates the production of adrenocortical
hormones
THYROTROPIN / THYROID STIMULATING HORMONE
(TSH)
Modulates thyroid hormone production in the
thyroid gland
PROLACTIN (PRL)
Promotes development of the mammary glands for
lactation
FOLLICLE STIMULATING HORMONE (FSH)
Promotes the development of oocyte/spermatocyte
LUTEINIZING HORMONE (LH)
Promotes estrogen/testosterone production

HORMONES POSTERIOR PITUITARY GLAND

VASOPRESSIN
Antidiuretic hormone
Regulates water reabsorption in the collecting
tubules (and the distal parts of the DCT) of the
kidneys
Produce vasoconstriction = vasopressin

OXYTOCIN
Uterine smooth muscle contraction
Milk letdown

FIGURE 4: Hypothalamic-Hypophyseal Tract and Blood Supply

CELLS OF ANTERIOR PITUITARY GLAND AND THEIR FUNCTIONS
SOMATOTROPHS

Hormone: SOMATOTROPIN (GH)

Stimulates growth in epiphyseal plates of LONG BONES via

(insulin-like growth factors) IGFs produced in the liver
LACTOTROPHS

MAMMOTROPHS

Hormone: PROLACTIN

Promotes MILK SECRETION

GONADOTROPHS

Hormone: FSH and LH; (Interstitial Cell Stimulating Hormone)

ICSH in men

FSH
o
Ovarian follicle development and estrogen
secretion in women
o
Spermatogenesis in men

LH
o
Ovarian follicle maturation and progesterone
secretion in women
o
Interstitial cell androgen secretion in mean
THYROTROPHS

Hormone: THYROTROPIN (TSH)

Stimulates Thyroid Hormone Synthesis,

Liberation

Storage,

and

CORTICOTROPHS

Hormones: ADRENAL CORTICOTROPIN (ACTH) and

LIPOTROPIN (LPH)

ACTH stimulates secretion of adrenocortical hormones

LPH helps regulate lipid metabolism

FIGURE 5: Hormones of Anterior and Posterior Pituitary Gland

HORMONES ANTERIOR PITUITARY GLAND

GROWTH HORMONE

GROWTH HORMONE (GH)

Promotes somatic growth
Protein
formation,
cell
differentiation

multiplication

ADRENOCORTICOTROPIC HORMONE (ACTH)

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Most abundant of the pituitary hormones

SOMATOTROPHS 50% of total Anterior Pituitary cell
population
SOMATOSTATIN synthesized in medial preoptic area of
hypothalamus and inhibits GH secretion
ESTROGEN induces GH

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ENDOCRINE
SYSTEM

Chronic glucocorticoid excess suppress GH release

LIVER and CARTILAGE greatest number of GH receptors
GH may decrease insulin sensitivity and this in turn leads to a
compensatory mechanism HYPERINSULINEMIA
Short half-life 20-15 minutes; when it reaches the liver it is
cleaved by the hepatic enzymes

ANTIDIURETIC HORMONE

SECRETION
GHRH stimulates GH synthesis and release
from the arcuate nucleus of the hypothalamus

GHRELIN directly stimulate GH release

IGF 1 / SOMATOMEDIN (Liver)

peripheral target hormone for GH FEEDS
BACK TO INHIBIT GH
mediate effects of GH

SRIF
paraventricular nucleus of hypopthalamus;
inhibits GH secretion
ACTIONS OF GH

LONGITUDINAL BONE GROWTH

o
As long as epiphyseal plates are still open
o
JAK-STAT receptor on cell membrane surface

MUSCLE MASS BUILD UP

o
Anabolic effect

LIPOLYSIS
o
Breakdown of stored fats; CATABOLIC
o
Leads to increased circulating fatty acid levels,
reduced omental fat mass, and enhanced lean
body mass

PROMOTES GLUCOSE TOLERANCE

o
Antagonizing insulin action

INDUCE
PROTEIN
SYNTHESIS
AND
NITROGEN
RETENTION

PROMOTES Na, K, and Water RETENTION

o
Elevates serum levels of inorganic phosphate

STIMULATES
EPIPHYSEAL
PRECHONDROCYTE
DIFFERENTIATION

Aka VASOPRESSIN
Released in response to rising plasma tonicity or falling blood
pressure
Activates two subtypes of G protein coupled receptors:
o
V1 - vascular smooth muscles and mediate
vasoconstriction
o
V2 renal tubule cells; REDUCE DIURESIS
through increased water permeability and water
resorption in the collecting tubules.
Secretion is regulated by the OSMOTIC PRESSURE of Body
Fluids

ACTIONS:
1)
2)
3)
4)
5)

Reduce water excretion by promoting concentration of urine

Increase hydroosmotic permeability of cells in the distal
tubules and medullary collecting ducts of the kidney
Causes contraction of smooth muscle in blood vessels and in
the GI tract
INDUCE GLYCOGENOLYSIS IN THE LIVER
Potentiate ACTH release by corticotropin-releasing factor
CLINICAL CORRELATION
ADH

DIABETES INSIPIDUS

GH- Stimulation on Cartilage and Bone Growth

Increase synthesis of DNA, RNA, Protein, HYDROXYPROLINE

Chondrocyte proliferation

Produce abnormally large volume of dilute urine

Deficiency in VASOPRESSIN
DESMOPRESSIN
o
Structurally modified version of vasopressin
o
Intranasal or PO
o
More selective for V2 than V1 receptors
o
Longer duration and better potency than
vasopressin
o
SE: Headache, N&V, abdominal cramps, allergy.
Overdosage: HYPONATREMIA and Seizures
o
ADV: VASOPRESSIN (But not Desmopressin) can
cause VASOCONSTRICTION and should be used
cautiously in patients with CORNOARY ARTERY
DISEASE

HYPONATREMIA
Cartilage proliferation

Widening of epiphyseal plate

New bone laid down

Excess vasopressin secretion

Results in production of decreased volume of more highly
concentrated urine
Results in excess water retention with expansion and dilution
of body fluids.
Syndrome of inappropriate antidiuresis
CAUSES: Exogenous administration of ADH, Desmopressin,
or large doses of Oxytocin.
GROWTH HORMONE

Linear Growth until closure of Epiphyseal plate

FIGURE 6: GH Stimulation of Cartilage and Bone Growth

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DEFICIENCY

CHILDREN
o
SHORT STATURE
o
Micropenis
o
Increased fat
o
High pitched voice

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ENDOCRINE
SYSTEM

o

Propensity to hypoglycemia due to relatively

unopposed insulin action

ADULTS
o
Reduced lean body mass
o
Increased fat mass with selective deposition of
intra-abdominal visceral fat
o
Increased weigh to hip ratio
o
Hyperlipidemia
o
Left ventricular dysfunction
o
HPN
o
Increased plasma fibrinogen levels
o
BONE MINERAL CONTENT IS REDUCED with
resultant increase in fracture rates
SOMATROPIN
o
Recombinant form of GH; subQ
MECASERMIN
o
Children with growth failure (severe IGF-1
deficiency) and unresponsive to exogenous
o
Complex of recombinant human IGF-1 and
recombinant human IGF binding protein 3.
o
subQ; 2x daily
o
SE:
HYPOGLYCEMIA,
intracranial
HPN,
asymptomatic elevation of liver enzymes

BUT DOES NOT ACTIVATE IT IT IS AN

ANTAGONIST)
SE

Worsening of GH secreting pituitary

tumors

Increase in levels of hepatic enzymes

(AST and ALT)
REFERENCES

Katzung, Masters and Trevor BASIC AND CLINICAL

TH
PHARMACOLOGY 12 EDITION
TH
Guyton and Hall TEXTBOOK OF MEDICAL PHYSIOLOGY 11
EDITION, 2006
TH
BERNE AND LEVY PHYSIOLOGY 6 EDITION
TH
SNELL CLINICAL ANATOMY 7 EDITION

EXCESS GROWTH HORMONE

ACROMEGALY

Abnormal growth of cartilage and bone tissue and many

organs including skin, muscle, heart, liver, and the GI tract.

GIGANTISM

GH secreting adenoma occurs before the long bone

epiphyses close

Rare condition
v

SOMATOSTATIN
o
Inhibits pituitary production of GH
o
Controls GH production
o
SHORT HALF LIFE as a drug (1-3 minutes)
OCTREOTIDE
o
Somatostatin analogue
o
45x more potent than somatostatin in inhibiting GH
release
o
Twice as potent in reducing insulin secretion
o
SUBQ q8
o
IM 4 week intervals
o
SE

N&V, Abdominal cramps, flatulence,

steatorrhea with bulky bowel movements

Biliary sludge and gallstones

Sinus bradycardia and conduction

disturbances

Pain at site of injection

B12 deficiency long term use of

Octreotide
PEGVISOMANT
o
PEG derivative of mutant GH
o
Partially activates GH receptor allowing
dimerization of the receptor but blocking the
conformation changes for signal transduction. (IN
SIMPLER TERMS, IT BINDS TO THE RECEPTOR

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