Second ppt on endocrine system, describing hypothalamus, pituitary and thyroid glands. This describes the hormones from these glands and their mode of action etc

1. Endocrine glands:
Hypothalamus, pituitary & thyroid
Radhakrishna G Pillai

2. Hypothalamus
• Hypothalamus is a major link between nervous and
endocrine system
• Pituitary attached to hypothalamus by infundibulum
– Anterior pituitary or adenohypophysis
– Posterior pituitary
or neurohypophysis

3. Anterior pituitary
– Release hormones by stimulatory or inhibitory
messages from the hypothalamus
– Also regulated by negative feedback
– Hypothalamic hormones made by neurosecretory
cells transported by hypophyseal portal system
– Anterior pituitary hormones that act on other
endocrine systems are called tropic hormones

4. Anterior Pituitary Hormones
• Human growth hormone (hGH) or somatostatin
– Stimulates secretion of insulin-like growth factors (IGFs) that promote
growth, protein synthesis
• Thyroid-stimulating hormone (TSH) or thyrotropin
– Stimulates synthesis and secretion of thyroid hormones by thyroid
• Follicle-stimulating hormone (FSH)
– Ovaries: initiates development of oocytes
– Testes: stimulates testosterone production

5. Anterior Pituitary Hormones
• Luteinizing hormone (LH)
– Ovaries: stimulates ovulation, Stimulate the production
of oestradiol
– helps to control the menstrual cycle
• After fertilization, LH stimulate the corpus luteum
• which produces progesterone to sustain the pregnancy
• Men: luteinizing hormone stimulates the production
of testosterone from Leydig cells in the testes
– Testosterone, in turn, stimulates sperm production and
– helps accentuate male characteristics — like deep voice or
growth of facial hair

6. Anterior Pituitary Hormones
• Prolactin (PRL)
– Promotes milk secretion by mammary glands
• Adrenocorticotropic hormone (ACTH) or
corticotropin
– Stimulates glucocorticoid secretion by adrenal cortex
• Melanocyte-stimulating Hormone (MSH)
– Unknown role in humans

8. Posterior pituitary
– Does not synthesize hormones
– Stores and releases hormones made by the
hypothalamus
• Transported along hypothalamo-hypophyseal tract
– Oxytocin (OT)
– Antidiuretic hormone (ADH) or vasopressin

9. Hormones stored in Posterior pituitary
Oxytocin
– During and after delivery of baby affects uterus and
breasts
– Enhances smooth muscle contraction in wall of uterus
– Stimulates milk ejection from mammary glands

10. Antidiuretic Hormone (ADH)
–Decreases urine
production by
causing the kindeys
to reabsorb more
water to the blood
–Also decreases water
loss through
sweating and
constriction of
arterioles which
increases blood
pressure
(vasopressin)

11. Thyroid Gland
• Located inferior to larynx
• 2 lobes connected by isthmus
• Thyroid follicles produce thyroid hormones
– Thyroxine or tetraiodothyronine (T4)
– Triiodothyronine (T3)
• Both hornones increase BMR
• Stimulate protein synthesis
• Increase use of glucose and fatty acids for ATP production
• Parafollicular cells or C cells produce calcitonin
– Lowers blood Ca2+ by inhibiting bone resorption

12. Control of thyroid hormone secretion
– Thyrotropin-releasing hormone (TRH) from
hypothalamus
– Thyroid-stimulating hormone (TSH) from anterior
pituitary
– Increase in ATP demand also increase secretion of
thyroid hormones

13. Control of Thyroid hormones
The thyroid
gland, anterior
pituitary gland,
and
hypothalamus
comprise a self-
regulatory circuit
known as
hypothalamic-
pituitary-thyroid
axis

14. TSH release
TRH acts via
phosphatidylinositol
4-phosphate (PIP)-
PKC and calcium
signaling

15. Calcium signalling in TH production
and release
• Calcium signaling involving phospholipase C is involved
• Calcium signaling is a process
– whereby the extremely low cytoplasmic Ca2+ concentration
increases
– in a deliberate and specific manner
– to trigger downstream cellular events
• Virtually every tissue, and even every cell type in the human body
utilizes some form of Ca2+ signaling to function or survive
• There are many mechanisms which can generate Ca2+ signals
• The most widely encountered is a mechanism involving a lipid
metabolizing enzyme phospholipase C

16. Phospholipase C signaling
• Only enzyme that can directly produce (or modulate) 3 distinct
signals:
– inositol 1,4,5-trisphosphate (IP3), diacylglycerol, and
– phosphatidylinositol 4,5-bisphosphate (PIP2)
• Initiating reaction is the breakdown of the lipid phosphatidylinositol
4,5 phosphate (PIP2) producing inositol 1,4,5 triphosphate
• This IP3 function as a Ca2+ signaling second messenger
• All three phospholipase C derived signals regulate ion channels
• Release of Ca2+ from intracellular stores (ER, microsomal fractions)
• Depletion of the endoplasmic reticulum Ca2+ pool activate
Ca2+ influx from extracellular fluid through plasma membrane

17. TSH
• TSH is released into the blood
• TSH binds to the thyroid-stimulating hormone receptor (TSH-R)
on the basolateral aspect of the thyroid follicular cell
• The TSH-R is a Gs-protein coupled receptor, and its activation
leads to the activation of adenylyl cyclase and
– Increase in intracellular levels of cAMP
• The increased cAMP activates protein kinase A (PKA)
• PKA phosphorylates different proteins to modify their functions

19. Formation and release of T3 and T4
• Monoiodotyrosine (MIT) and diiodotyrosine (DIT) are generated
in thyrocytes
• MIT has a single iodine residue in tyrosine, and DIT has two
iodine residues in tyrosine
• Thyroid peroxidase (TPO) combines iodinated tyrosine residues
to make triiodothyronine (T3) and tetraiodothyronine (T4)
• One each of MIT and DIT join to form T3, and two DIT molecules
form T4
• Thyroid hormones are bound to thyroglobulin and stored in the
follicular lumen

20. Release of thyroid hormones
• Thyrocytes uptake iodinated thyroglobulin via endocytosis
• Lysosome fuse with the endosome containing iodinated
thyroglobulin
• Thyroglobulin is cleaved into MIT, DIT, T3, and T4 by Proteolytic
enzymes in the endolysosomes
• T3 (20%) and T4 (80%) are released into the fenestrated capillary
network via the transporter MCT8
• Deiodinase enzymes remove iodine molecules from DIT and MIT
• Iodine can be salvaged and redistributed to an intracellular
iodide pool

21. T3 & T4
• Thyroxine (T4) is the predominant secretory product of the
thyroid gland
• Only 20% of the circulating T3 are secreted directly by the thyroid
• In the periphery T4 is deiodinated supplying roughly 80% of the
circulating triiodothyronine (T3)
• Synthesis and release of T4 and T3 are inhibited when hormone
levels in plasma exceed a pre-set level
• To a large extent, TRH defines this pituitary-thyroid axis set point
and contributes to the maintenance of homeostasis of
the plasma hormone levels
• In the pituitary TRH regulates not only the secretion of TSH but
also its bioactivity required for correct receptor binding

22. Transport of Thyroid Hormones
• Thyroid hormones are lipophilic and circulate bound to the
transport proteins
• Transporter proteins include thyroxine-binding globulin
(TBG), transthyretin, and albumin
• Only a fraction (~0.2%) of the thyroid hormone (free T4) is
unbound and active
• On reaching the target site, T3 and T4 can dissociate from
their binding protein
• Enter cells either by diffusion or carrier-mediated transport

23. Receptor binding
• Thyroid receptors are transcription factors that
can bind to both T3 and T4
• They have a much higher affinity for T3
• As a result, T4 is relatively inactive
• Deiodinases convert T4 to active T3 or inactive
reverse T3 (rT3)

24. Physiological roles of Thyroid hormones
• Thyroid hormone affects virtually every organ
system in the body
• In general, the thyroid hormone binds to its intra-
nuclear receptor
• This activates the genes for increasing metabolic
rate and thermogenesis
• Increasing metabolic rate involves increased
oxygen and energy consumption

25. Physiological effects of thyroid hormones
• Increases the basal metabolic rate
• May induce lipolysis or lipid synthesis depending on
metabolism
• Stimulate the metabolism of carbohydrates
• Anabolism/catabolism of proteins
• Permissive effect on catecholamines
• In children, thyroid hormones act synergistically with
growth hormone to stimulate bone growth

26. Thyroid hormones on central nervous
system
• During the prenatal period, thyroid hormones are
needed for the maturation of the brain
• In adults, it can affect mood
– Hyperthyroidism can lead to hyper excitability and
irritability
– Hypothyroidism can cause impaired memory, slowed
speech, and sleepiness
• Thyroid hormone affects fertility, ovulation, and
menstruation

27. Effect on different organs
• Heart: TH have a permissive effect on
catecholamine
• It increases the expression of beta-receptors to increase heart
rate, stroke volume, cardiac output, and contractility.
• Lungs: TH stimulate the respiratory centers:
increase perfusion & increase oxygenation
• Skeletal muscles: increased development of type II
muscle fibers
– These are fast-twitch muscle fibers capable of fast and
powerful contractions

28. TH Physiological role
• Metabolism: TH increases the basal metabolic rate
– increases the gene expression of Na+/K+ ATPase in different
tissues leading to increased oxygen consumption, respiration
rate, and body temperature
– TH do not change the blood glucose level, but they can cause
increased glucose reabsorption, gluconeogenesis, glycogen
synthesis, and glucose oxidation.
• Growth during childhood
– TH act synergistically with growth hormone to stimulate bone
growth
– It induces chondrocytes, osteoblasts, and osteoclasts
– Also helps with brain maturation by axonal growth and the
formation of the myelin sheath

29. TH in action
• Receptors for T3 remain bound to the DNA in nucleus
• T3 /T4 then bind to nuclear α/β receptors in the tissue
• Cause activation of transcription factors
• Activation of certain genes and cell-specific responses
• TH are degraded in the liver via sulfation and
glucuronidation
• Degraded products excreted in the bile

30. Radhakrishna G Pillai
Pillai_radhakrishna@hotmail.com
0091 9495554891
Thank
You