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And metabolism
YUNIADI SUTOWO
Adrenal Cortex Hormones
The adrenal cortex comprises three
zones, or layers:
1- Zona glomerulosa: The outermost layer, main site
for production of mineralocorticoids, mainly
aldosterone, which is largely responsible for the
long-term regulation of blood pressure.
3
21 C
22
20 C 26
23
12 24 25
18 17
11 16
KOLESTEROL 13 27
C D
1 19 9
14 15
2
10 8
A B
3
7
5
OH 4 6
A,B,C,D
STEROID HASIL DARI
KORTEKS ADRENAL
Steroid
+
Target cell
Hsp90
SRC
Activated
SRC = Steroid
receptor Hsp90
complex
DNA
Hsp90
mRNA
New Protein
Biological protein synthesis
response
Steroid receptor complex in cytoplasm binding steroid activates and moves to nucleus
HORMONE OR EFFECTOR HRE DNA SEQUENCE
GLUCOCORTICOID GRE
PROGESTINS PRE GGTACA NNN TGTTCT
MINERALOCORTICOIDS MRE
ANDROGENS ARE
21 OH ASE
11 DEOKSIKORTIKOSTERON 11 DEOKSIKORTISOL
TESTOSTERON
11 OH ASE
KORTIKOSTERON KORTISOL
18 OH ASE
18 0H KORTIKOSTERON KORTISON
18 OH DEHIDROGENASE
ALDOSTERON
CH2
H
CH2H
C0
C0 CH3
0 0H
CH3 0H
0H H3C
0
kortison
kortisol
(hidrokortison)
CH2H
C0
CH3
CH2
H
CH3 C0 CH3
0H
CH3 0
0 11 deoksikortikosteron
kortikosteron
THE BIOLOGIC ACTIVITY OF A
STEROID DEPENDS ON:
1. Its ability to bind to a receptor
2. Concentration of free hormone in the plasma
Cortisol, corticosterone, and aldosterone all
bind with high affinity to the glucocorticoid
receptor
However, cortisol is dominant because of its
high plasma concentration
RESEPTOR
MINERALOKORTIKOID
TIPE I DAN II DIGUNAKAN MENGIKAT
MINERALOKORTIKOID,
TIPE II JUGA MENGIKAT HORMON
GLUKOKORTIKOID.
AFINITAS MINERALOKORTIKOID PADA
TIPE III SANGAT RENDAH.
AFINITAS ALDOSTERON
TERHADAP RESEPTOR NYA
KADAR ALDOSTERON DARAH LEBIH KECIL DPD KADAR
DOC, KORTISOL DAN KORTIKOSTERON. NAMUN
IKATAN ALDOSTERON TERHADAP RESEPTOR
MINERALOKORTIKOID TIPE I LEBIH KUAT DPD IKATAN
TERHADAP DOC, KORTISOL DAN KORTIKOSTERON
OLEH KARENA:
18
Cortisol: Regulation & Transport
Cortisol secretion is under control of the hypothalamic-Pituitary-
Adrenocortical axis as in figure.
D- Other Effects:
It has potent anti-inflammatory and
immunosuppressive properties.
Impair phagocytic activity and migration of white blood
cells; Reducing production of PG and leukotrienes
Prevent edema; Reduce capillary permeability.
Dr. Manal Basyouni 24
EFFECTS OF GLUCOCORTICOIDS
1. AGONIS
2. AGONIS PARSIAL
3. ANTAGONIS DAN ANTAGONIS PARSIAL
4. STEROID INAKTIF
GANGGUAN FUNGSI KORTEKS
ADRENAL
I. INSUFISIENSI ADRENAL PRIMER
( PENYAKIT ADDISON )
TJD PENURUNAN GLUKOKORTIKOID, SEHINGGA TJD
PENINGKATAN ACTH DAN POMC ---
HIPERPIGMENTASI .
MINERALOKORTIKOID, ANDROGEN JUGA MENURUN.
II. INSUFISIENSI ADRENAL SEKUNDER
TJD PENURUNAN GLUKOKORTIKOID DAN ANDROGEN
DARAH AKIBAT PENURUNAN ACTH----- TIDAK TERJADI
HIPERPIGMENTASII
GANGGUAN FUNGSI
KORTEKS ADRENAL
Cushing disease
caused by excessive secretion of ACTH by
pituitary tumor ( pituitary adenomas )
The most common symptom of Cushing's
syndrome is sudden weight gain, usually
manifested by central obesity.
Multiple wide striae on
the abdomen of a patient
with Cushing's disease.
http://www-clinpharm.medschl.cam.ac.uk/images/addisons.jpg
Hyper-
adrenocorticism
Post-surgery
Untreated Cushings Syndrome
Laboratory studies of
adrenocorticol functions
1. ACTH stimulation test
2. Dexamethasone suppression test
3. Metyrapone/Metopirone stimulation test
4. Insulin hypoglycemia test
5. Plasma total cortisol