Adrenocorticotropic Hormone (Corticotropin)

 Stimulates the adrenal cortex to release

corticosteroids
 Triggered by hypothalamic corticotropin-releasing
hormone (CRH) in a daily rhythm
 Internal and external factors such as fever,
hypoglycemia, and stressors can trigger the release
of CRH

Department of Physiology Diponegoro University Faculty of Medicine

 Corticotropin Feedback Loops

The controlofpathway
Department for cortisol
Physiology Diponegoro University Faculty of Medicine
 Gonadotropins

 Gonadotropins – follicle-stimulating hormone (FSH)

and luteinizing hormone (LH)
 Regulate the function of the ovaries and testes
 FSH stimulates gamete (egg or sperm) production
 Absent from the blood in prepubertal boys and girls
 Triggered by the hypothalamic gonadotropin-
releasing hormone (GnRH) during and after
puberty

Department of Physiology Diponegoro University Faculty of Medicine

 Functions of Gonadotropins

 In females
 LH works with FSH to cause maturation of the
ovarian follicle
 LH works alone to trigger ovulation (expulsion of
the egg from the follicle)
 LH promotes synthesis and release of estrogens and
progesterone

Department of Physiology Diponegoro University Faculty of Medicine

 Functions of Gonadotropins

 In males
 LH stimulates interstitial cells of the testes to
produce testosterone
 LH is also referred to as interstitial cell-stimulating
hormone (ICSH)

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 Prolactin (PRL)

 In females, stimulates milk production by the breasts

 Triggered by the hypothalamic prolactin-releasing
hormone (PRH)
 Inhibited by prolactin-inhibiting hormone (PIH)
 Blood levels rise toward the end of pregnancy
 Suckling stimulates PRH release and encourages
continued milk production

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine
Department of Physiology Diponegoro University Faculty of Medicine
Department of Physiology Diponegoro University Faculty of Medicine
Department of Physiology Diponegoro University Faculty of Medicine
 The Posterior Pituitary and Hypothalamic
Hormones
 Posterior pituitary – made of axons of hypothalamic
neurons, stores antidiuretic hormone (ADH) and
oxytocin
 ADH and oxytocin are synthesized in the
hypothalamus
 ADH influences water balance
 Oxytocin stimulates smooth muscle contraction in
breasts and uterus
 Both use PIP-calcium second-messenger mechanism
Department of Physiology Diponegoro University Faculty of Medicine
 Oxytocin

 Oxytocin is a strong stimulant of uterine contraction

 Regulated by a positive feedback mechanism to
oxytocin in the blood
 This leads to increased intensity of uterine
contractions, ending in birth
 Oxytocin triggers milk ejection (“letdown” reflex) in
women producing milk

Department of Physiology Diponegoro University Faculty of Medicine

 Oxytocin

Department of Physiology Diponegoro University Faculty of Medicine

 Oxytocin

 Synthetic and natural oxytocic drugs are used to

induce or hasten labor
 Plays a role in sexual arousal and satisfaction in
males and nonlactating females

Department of Physiology Diponegoro University Faculty of Medicine

 Antidiuretic Hormone (ADH)

Department of Physiology Diponegoro University Faculty of Medicine

 Antidiuretic Hormone (ADH)

 ADH helps to avoid dehydration or water overload

 Prevents urine formation
 Osmoreceptors monitor the solute concentration of the
blood
 With high solutes, ADH is synthesized and released,
thus preserving water
 With low solutes, ADH is not released, thus causing
water loss from the body
 Alcohol inhibits ADH release and causes copious urine
output
Department of Physiology Diponegoro University Faculty of Medicine
 Thyroid Gland

 The largest endocrine gland, located in the anterior

neck, consists of two lateral lobes connected by a
median tissue mass called the isthmus
 Composed of follicles that produce the glycoprotein
thyroglobulin
 Colloid (thyroglobulin + iodine) fills the lumen of
the follicles and is the precursor of thyroid hormone
 Other endocrine cells, the parafollicular cells,
produce the hormone calcitonin
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 Thyroid Gland

Department of Physiology Diponegoro University Faculty of Medicine

Department of Physiology Diponegoro University Faculty of Medicine
 Histologic Section of Normal Thyroid

C cells

Follicular
colloid cells

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 Thyroid Hormones
 Thyroid hormone – the body’s major metabolic
hormone
 Consists of two closely related iodine-containing
compounds
 T4 – thyroxine; has two tyrosine molecules plus
four bound iodine atoms
 T3 – triiodothyronine; has two tyrosines with three
bound iodine atoms
 Calcitonin

Department of Physiology Diponegoro University Faculty of Medicine

 Thyroid Hormones
OH OH
I I I

O O
I I I I

CH2 CH2
NH2CHCOOH NH2CHCOOH
Thyroxine (T4) Triiodothyronine (T3)

Department of Physiology Diponegoro University Faculty of Medicine

 Synthesis of T3 and T4
 Thyroglobulin is synthesized and discharged into the
lumen
 Iodides (I–) are actively taken into the cell, oxidized
to iodine (I2), and released into the lumen
 Iodine attaches to tyrosine, mediated by peroxidase
enzymes, forming T1 (monoiodotyrosine, or MIT),
and T2 (diiodotyrosine, or DIT)
 Iodinated tyrosines link together to form T3 and T4
 Colloid is then endocytosed and combined with a
lysosome, where T3 and T4 are cleaved and diffuse
into the bloodstream
Department of Physiology Diponegoro University Faculty of Medicine
 I + tyrosine monoiodotyrosine (MIT)

MIT + I diiodotyrosine (DIT)

DIT + DIT thyroxine (T4)

DIT + MIT triiodothyronine (T3)

hormones still attached to thyroglobulin

Department of Physiology Diponegoro University Faculty of Medicine

 Synthesis of Thyroid Hormone

Department of Physiology Diponegoro University Faculty of Medicine

 Transport and Regulation of TH

 T4 and T3 bind to thyroxine-binding globulins

(TBGs) produced by the liver
 Both bind to target receptors, but T3 is ten times
more active than T4
 T3 also being produced in the peripheral tissues by
deiodination of T 4 (~ 80% of T 3 )
 reverse T 3 (rT 3 ) is inactive
 Mechanisms of activity are similar to steroids
 Regulation is by negative feedback
 Hypothalamic thyrotropin-releasing hormone (TRH)
can overcome the negative feedback
Department of Physiology Diponegoro University Faculty of Medicine
 T3 and T4

• Bound to carrier proteins in the plasma

- thyroid binding globulin (TBG)
- albumin (10%)
- transthyretin (20%)
• Mainly thyroxine (t4) is released
- T4:T3 ratio = 25
- T3 is formed by the deiodination of T4

Department of Physiology Diponegoro University Faculty of Medicine

 Iodine metabolisme
• The minimum adult daily requirement to maintain
thyroid function ±100-150 µg
• The thyroid secretes ±80 µg of I- per day as T3 &
T4, of which ±60 µg is metabolised in the liver
with release of I- into the ECF
• The total I- added to the plasma per day :
 500 µg - average dietary intake
 60 µg - from the liver metabolism of T3
& T4
 40 µg - diffusion from the thyroid to the
ECF

Department of Physiology Diponegoro University Faculty of Medicine

 Iodine metabolisme

About 600 µg of iodide is distributed throughout

the ECF daily:
• Thyroid takes up ~ 20% or ~ 120 µg/day
• Remaining 80% is taken up by the kidney and
excreted in the urine

Department of Physiology Diponegoro University Faculty of Medicine

 Physiological Actions of Thyroid Hormones

• effects of T3 and T4 are nearly identical except for

latency and potency

• essential for growth in childhood

• various metabolic effects:

- increase breakdown of carbohydrates

- increase breakdown of lipids
- determine metabolic rate
- level of heat production
Department of Physiology Diponegoro University Faculty of Medicine
 Effects on Organ Systems

• HEART – increases rate, decreases force

• VASCULAR – vasodilation

• GI – increased motility and absorption

• SKELETAL – increased bone turnover

• NEUROMUSCULAR – hyperactivity, increased

muscle contraction

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 Thyroid Hormone Control Pathways

Thyroid of
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Medicine
 Additional Mechanism of T3/T4 Release

Cold exposure:
• a decrease in temperature acts via the
hypothalamic thermoregulatory centre to
increase release of TRH

• an increase in temperature has the reverse

effect

Department of Physiology Diponegoro University Faculty of Medicine

 TPOAb= Thyroid Peroxidase Antibody

Department of Physiology Diponegoro University Faculty of Medicine

 • Increase in thyroid binding globulin due to increase in
estrogen (stimulation of hepatic production and
decreased degradation)
 Increase in total T4 and T3
• Increase in GFR leads to increase in renal iodine
clearance
• HCG has similar properties to TSH therefore has
intrinsic thyroid stimulating activity
 Increase FT4 and FT3 levels during first trimester

Department of Physiology Diponegoro University Faculty of Medicine