ENDOCRINOLOGY

Three Main concepts

V v
CONCEPT OF Is'1 & 2NU GENERALIZATION OF UNDERSTANDING
MESSENGERS SECOND MESSENGER HORMONES
SYSTEM
1. Messenger system
a. 1st Messenger: -
A molecule outside the cell, that initiates specific eent in the cell eg Hormone.
b. 2nd Messenger:.
Molecule inside the cell, which triggers physiologic changes in response to first
messenger.
Example C-AMP C-GMP
GENERALIZATION OF MECHANISM OF HORMONE’S ACTION
1. IP3-DAG:-
All the hypothalamic hormones use IP3-DAG mechanism, except CRH-> that uses C-
AMP.
2. Cyclic -GMP:-
It is used by 2 important hormones e.g no -ANP.
3. Tyrosine -Kinase:- used by anabolic hormones i.e the hormones causing synthesis of
molecules e.g . insuline, erythropoietin , growth hormones etc.
4. Action on Genes / nucleus: This mechanism is used by steroid hormones and
thyroxin.
Cyclic - AMP :. All the hormones not fitting into above categories e.g ACTH, FCH, LH.
HYPOTHALAMUS HORMONE

V V V

TRH GHRH

P.I.F/ Prolactin INh Factor

i 1 i
TTSH iProlactin TGH
TProlactin

V V V

Somato
GnRH CRH
statin

i i
TFSH TACTH iGH
TLH
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PITUITARY HORMONES

I
GROWTH HORMONE
i
1.
2.
TSH, FSH, LH
Polypeptide
Secretion is increased by 3-s
a. Sleep (NREMttt)
b. Stress (e.g exercise)
c. Starvation
3. Secretion is inhibited by SHOP ■4 Somatization
-4 Hyperglycemia -4 Obesity 4 Pregnancy
4. Action
Direct Indirect
a. Inc proteins IGF
synthesis a. Inc protein
b. Inc lipolysis synthesis in
c. Dec glucose chondrocytes
utilization by increases
i.e causes linear growth
hyperglycemia b. Inc protein
synthesis in
!- muscles and
viscera, that’s
how it inc
lean body
mass and
causes
visceromegaly

3.
Y
ACTH
Y
PROLACTIN
2.
Details on next Page
FSH
Stimulates ovarian follicles as name indicates & inc estrogen secretion.
Sperm Maturation -4 means on one side it cause sperm to mature and on other side the
ovum, so it’s important in maintaining fertility.
LH -4 hormones producer hormone eg.
• In females, it causes ovulation, then corpus leutium formation -> that secrets
progesterone and estrogen.
• Male -> synthesis and secretion of testosterone.
TSH:
Stimulates thyroid gland
PITUITARY HORMONES
CONTAINS
y y
ACTH
• Stimulates the secretion of
1. Cortisol
2. Secretion of Sex steroids But not aldosterone , that’s under the control of
angiotensin- II
=> Point of the Day
PROLACTIN • Polypeptide

Stimulated by Inhibited by
• Estrogen • Dopamine and
• Pregnancy it’s agonist.
• Breast feeding • Somatostatin
• Sleep & stress
• TRH
• Dopamine
antagonist
Function of
Prolactin:-
1. Milk
production
2. Breast
development
3. Inhibits
ovulation
Somatostatin is the master of inhibition and makes many hormones static e.g GH,
Prolactin , insulin. Glucagon and go on.
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CALCIUM METABOLISM & PARATHYROID HORMONE
Total serum Ca
V
Tee i.e
onised Ca++ (47%)
It is the active form of Ca++ , and inc or decrease secretion of PTH accordingly In
Nutshell -LCa+2 oct PTH Note that, vitamin -D is hydroxylated at 25 in liver and at 1 in
kidney by 1 oc hydroxyl ate.
PTH activate vitamin D . synthesis and activation via stimulation of 1 oc hydroxylase
Bound
Bound to Albumin Bond to Phosphate
40%
And citrate (13%)
Note : Albumin is negatively charged, that binds positively charged Ca++
If there is acidosis , that means there is excess of H+ ions , and that H+ will displace Ca++
and binds by itself to albumin. That displaced Ca+2, will cause hypercalcemia.
If there is alkalosis, there will be excess of OH' ions, and Ca++ will binds that OH' this will
result in hypo-calcemia. Conclusion
Acidosis => Hypercalcemia
Alkalosis =>Hypocalcemia

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SUMMARY OF ACTION OF P.T.H & VIT-D,
¥

Intestine Kidney Bona

1. PTH: increases Ca++ absorption via activation of VIT D3
2. VIT-D3:
=> Increase calcium absorption Ga (calbindin D-28-K). this is through gene activation,
because vit D3 is a steroid hormone. => increase phosphate absorption.
1. PTH
Inc Ca++ reabsorption Dec POT3 reabsorption
2. VIT-D increase Ca++ and PO4J reabsorption i.e ion both Ca++ & POT3.
1. PTH Increase Bone resorption
2. VIT-D3
Increase bone resorption.
Important points.
1. PTH => inc calcium and Dec phosphate in blood.
2. Vit D3 => inc calcium and inc phosphate in blood.
3. Mild magnesium deficiency T PTH =» Hypercalcemia
4. Severe Mg deficiency : i PTH Hypo Calcemia
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POSTERIOR PITUITARY

Oxytocin : From Periventricular nucleus

Function ADH : From supra-optic nucleus
1. Ejection of breast milk , for which major stimulus is suckling.
2. Ejection of baby from uterus i.e contraction of uterus during labour.
Stimulants Nausea => most powerfiill one T serum osmo Hypoglycemia
Inhibitors
• Alcohol -> major one
• i serum osm
Site of action : Later distil convoluted tubules (DCT) and collecting ducts.
1. Inc water absorption via V2 receptors
2. Vasoronstriction via VI receptors
THYROID GLAND
=> Synthesis of thyroid hormones in follicular cell.
City Scan cTPtQfi:itQ:fl/7 SSftt/7/A
Summary
Look back at the figure, the first step is Iodine transport, then next 3 steps are
mediated by enzyme peroxidase, ten endocytosis and next two steps, are by 2 enzymes
i.e I 5y.idoinase and deiodenase.
CONCEPT OF TOTAL & ACTIVE THYROID HORMONE
To circulation total thyroid home is in 2 forms i.e free thyroid hormone and bound-form (
bound to thyroid binding globulin-TBG.
Total =TBG-Bound hormone + Free Hormone
;
Note That:
Free hormone is active hormone
The free hormone is constant, so in conditions like liver failure. TBG decrease. That
decrease total hormone, but patient is still normal of from thyroid hormone effects
because free hormone is not affected.
In similar way during pregnancy TBG increases and also the total hormone, but the
patient /person is normal, as again free hormone is normal.
EFFECTS OF THYROID HORMONE
 EFFECT/ACTION
1. Increase bas of metabolic rates oxygen
consumption etc but not in brain,
spleen and gonads.
2. Increases C.V.S activity i.e Heart rate
3. Increases respiration
4. Catabolic effects
MECHANISM
Thyroid hormone inc the activity of Na-
K-ATpase , that use, more energy anc
=s> oxygen.
Thyroid hormone inc B1 receptors or.
heart, and hence the activity in
==>
response to sympathetic nervous
system increase.
It’s the response to more oxygen
consumption and CO2 production.
=> Increase the degradation of proteins A
that cause, wasting lipids and ever
cholesterol. Level in hyperthyroidism.

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Note:
Prenataly (during intrauterine life) thyroid hormone is responsible for brain (CNS)
formation.
Also
Synergistically, thyroid hormone with growth , regulates the body growth / bone growth .
CRH. ACTH & ADRENAL GLAND
i

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SYNTHESIS OF ADRENAL HORMONE
Cholesterol
v/
Pregne-nolone
17-Hydroxylase
17-HO-Pregninolone.
v
Progesteron 17-Hydroxylase
21 -Hydroxylase
v
Weak Mineralo- Corticoid 11 Hydroxylase
17-OH-Progesteron ■
^Dihydro-EPI-
Androsterone
-> Andro-Steren-Dione
Aldosterone
21 -Hydroxylase
Intermediate to Cortisol
11 -Hydroxylase
V
Cortisol
V
Testosterone
5areductase Androgen Aromatase Estradiol
I fl

MH
FUNCTIONS OF ALDOSTERONE
Site of action:
Late dct and connecting ducts.
=>It acts on 2 cells: Principle cells and intercalated cells.
Principle cells
Urine
Blood
In nut-Shell aldosterone, cause reabsorption and KT & H secretion that result in
• Hypokalemia (due to K+ loss)
• Alkalosis ( due to H+ loss)
Normally Hypernatremia does not develop because with every Na+ ion, three molecules
of water are absorbed, that causes dilution.
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If there is excess of aldosterone, Na+ is absorbed in a fairly huge quantity, that may
cause hypernatremia with increased BP.
CLINICAL CORRELATION:
1. Addison disease: Means aldosterone deficiency so revers the action of aldosterone.
• Hyperkalemia • Acidosis • Hypernatremia • Hypotension
2. Conn’s syndrome: Inc aldosterone so enlist its actions
• Hypokalemia • alkalosis • Hypertension etc.
Note that: Here acidosis and alkalosis means metabolic acidosis / alkalosis
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ACTIONS OF CORTISOL
DIRECT EFFECTS
1
INDIRECT EFFECTS

1. Gluco-neo genesis i.e it inc blood sugar, that’s why cortisol is diabetogenic
2. Increase Lipolysis, to provide glycerol for gluco-ne-genesis
3. Proteolysis :
Provides amino acid, for gluconeogenesis.
^ Weakens / breaks collagen producing straie on body
^ Weakens bones as bones too have proteins causing osteoporosis.
Dec muscle mass due to lipolysis and protein break down.
4. -> Inhibits phospholipase enzyme => acts as anti-inflammatory agent.
5. -> inhibits IL2 -> Dec lymphocytes
6. -> upgrade by receptors (esp alpha 1) in blood vessels and causes vasoconstriction
that inc BP.
7. -> induces apoptosis in eisrtophills & acts as anti-allergic .
8. -> breaks the attachement of merginated nutrophills to blood vessels inc nutrophills
in blood.
Note that the protolithic action of cortisol effects
Skin That becomes this
Lens -> that cause cataract
Blood vessel, -> streie
Muscle -> weakness etc.
1. Causes typical moon fascist and control.
Obesity:
Mechanism => If increase blood glucose, that inc the secretion of insulin, Insulin
increases the deposition of fats causing control obesity and moon fascist.
2. Increase androgens that cause. Hirustism and virlization
proteins everywhere in the body e.g.
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CLINICAL CORRELATIONS:
1. Cushing syndrome: Means exess cortisol =>so enlist all actions of cortisol
2. Cushing disease: means excess cortisol ==» so enlist all actions of cortisol plus there
is hyperpigmentation due to inc ACTH.
SEX-STEROIDS
ZONE A RETICULARIS PRODUCE SEX-STEROIDS
------------------------------------- 2 CLASSES
17-Keto Steroids Others =» while these are
These are ' Testosterone
Di-Hydro -epi- Andosteron (DHEA) 5 reeducates
And Androgen
Andostemdione (Note that androgen is converted
To estrogen by aromatase enzyme In peripheral tissues)
CLINIC Al, CORRELATES:
1. 21 — /? Hydroxylase deficiency : means
• Dec cortisol -> enlist it’s deficiencies
• Dec Aldosterone enlist aldosterone deficiency
• Inc sex-steroids, that may cause
Inc virilization , in women , early appearance of axillaiy and pubic hair, accelerated linear
growth etc.
It’s the most common disorder of this pathway.
2. 11- /? Hydroxylase deficiency
• Dec cortisol
• Inc Sex-steroid
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Nearly normal aldosterone-intermediates that have mineralocorticoid activity.

MALE REPRODUCTIVE HORMONES
v
HYPO-THALAMAS
(ARCUATE NUCLEUS)
GnRH

IMPORTANT POINTS
1. Lesion of arcuate nucleus kallman syndrome
2. Pulsatile release of GnRH initiates Puberty.
3. To memorize FSH action: Look At “S” in FSH, Sertoli and Sperms. That means FSH acts
on sertoli cells to produce mature sperms.
4. To memorize LH Action: Look At “L” in LH and Leydig cells : that means LH acts on
leydig cells to produce testosterone.
FEMALE REPRODUCTIVE HORMONES
. HYPO-THALAMUS
GnRH
V
ANT- PITUITARY

Note: Aromatase under the action of Note: LH as used produces testosterone

FSH converts testosterone into Estrogen. (But here cells are Theca) i.e T for theca. T
for testosterone
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FOUR PHASES OF MENSTRUAL CYCLE
PHASE OF CYCLE EFFECTS OF PHASE
1. Follicular phase: INC ESTROGt ;N SYNTHESIS
• Estrogen dominate • • Estrogen causes proliferation
Estrogen up regulates FSH
• 0-14 days & LH receptors on of uterus i.e proliferative
• Actually 0-9 days is granulosa & THECA cells. phase.
menstrual phase. • FSCH & & LH Levels are
suppressed by -ve feed
back action of estrogen on
ant-pituitary.
2. Ovulation day -14 Now estrogen via postive feed- backe inc LH and FSH,
but LH is more, that, why it is called LH surge so -Day
-14. |
^ i'
LH Surge.& estrogen Ovulation Thining of cervical
Burst mucus to make way
Easier for sperm.
3. Luteal phase day 14-28 PROGEST^RON DOMINANY
vj/ \|/
Corpus Leutum If no ferilization Progesterone
formation That then corpus leutium i
> estrogen. tV
i' ■ Inc body temp via
Inc vascularity oJ Endometrium hypothalamic
i.e Secretory phase. Centers
4. Menstrual Phase: 0-4
days:
Abrupt withdrawl of
estrogen and progesterone
endometrium sloughs off
IMPORTANT POINTS REGARDING MENSTRUAL CYCLE AND FEMALE HORMONES
In previous discussion, you may have noted that estrogen is unique; it both inhibits and,
stimulates FSH and LH serration.
Steady Rise in estrogen -> inhibits FSH and LH Burst of estrogen -> stimulate. FSH and
LH.
Note that: the last 14 days of menstrual cycle are fixed if you want to know the day of
ovulation. Subtract thse fixed 14 from total period.
e.g Total period is 28 dyas there.
Day of ovulation = 28-14 =14th day
If period is 35 days.
Day of ovulation = 35 -14 = 21st day.
 During pregnancy placenta produces estrogen that is Estriol ^ Post-menopausal lady
produces Estrone
LACTATION
• Estrogen stimulates prolactin
• Prolactin promotes lactation
During pregnancy lactation does not occur. Because estrogen and progesterone block
the action of prolactin on breast.
Note: Estrogen »> Progesterone in blocking effect.
[
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j no

LOCATION «JAL AMMENORREA

Due to thi 3se effect of prolactin

I
1
Inhibits
hypothalamic GnRH secreation and also inhibits it’s action on anterior pituitary
• Inhibits the release of FSH and LH from anterior pituitary
Antagonize the action of FSH and LH on ovary
Ill
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